2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T447,This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group (P < .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]).31:Taee,Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Secondary end points included all-cause mortality. This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group (P < .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]). In high-risk patients without known significant atherosclerosis and with diabetes, evolocumab reduced the risk of a first major cardiovascular event. ClinicalTrials.gov Identifier: NCT03872401.32:T11e8, Importance Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. Objective To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. Design, Setting, and Participants VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. Intervention Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. Main Outcomes and Measures The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Secondary end points included all-cause mortality. Results This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group ( P &lt; .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]). Conclusions and Relevance In high-risk patients without known significant atherosclerosis and with diabetes, evolocumab reduced the risk of a first major cardiovascular event. Trial Registration ClinicalTrials.gov Identifier : NCT03872401 33:T6f6,Cardiac allograft vasculopathy is an important cause of mortality after heart transplantation (HT). Dyslipidemia is a major contributor to the development of cardiac allograft vasculopathy. The safety and effectiveness of proprotein convertase subtilisin/kexin 9 inhibition to lower cholesterol and to prevent cardiac allograft vasculopathy early after HT are not well established. In this investigator-initiated, prospective, multicenter, double-blind randomized trial, participants were randomized early after HT to receive either alirocumab or placebo in addition to rosuvastatin. Before randomization and at 1 year, all participants underwent invasive coronary assessment, including angiography, fractional flow reserve, coronary flow reserve, the index of microcirculatory resistance, and intravascular ultrasound with near-infrared spectroscopy. Lipid values were assessed at baseline and at prespecified intervals. The primary end point was the change in coronary artery plaque volume from baseline to 1 year after HT based on serial intravascular ultrasound. A total of 114 HT recipients were included (57 assigned to alirocumab and 57 assigned to placebo). Baseline characteristics were well matched between the 2 groups. The low-density lipoprotein cholesterol levels decreased significantly from baseline to 1 year in the alirocumab arm (72.7±31.7 to 31.5±20.7 mg/dL; Proprotein convertase subtilisin/kexin 9 inhibition with alirocumab in addition to statin therapy early after HT safely lowers low-density lipoprotein cholesterol but did not reduce coronary artery plaque progression after 1 year compared with rosuvastatin alone in patients with a low baseline low-density lipoprotein cholesterol. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537742.34:Tf39, BACKGROUND: Cardiac allograft vasculopathy is an important cause of mortality after heart transplantation (HT). Dyslipidemia is a major contributor to the development of cardiac allograft vasculopathy. The safety and effectiveness of proprotein convertase subtilisin/kexin 9 inhibition to lower cholesterol and to prevent cardiac allograft vasculopathy early after HT are not well established. METHODS: In this investigator-initiated, prospective, multicenter, double-blind randomized trial, participants were randomized early after HT to receive either alirocumab or placebo in addition to rosuvastatin. Before randomization and at 1 year, all participants underwent invasive coronary assessment, including angiography, fractional flow reserve, coronary flow reserve, the index of microcirculatory resistance, and intravascular ultrasound with near-infrared spectroscopy. Lipid values were assessed at baseline and at prespecified intervals. The primary end point was the change in coronary artery plaque volume from baseline to 1 year after HT based on serial intravascular ultrasound. RESULTS: A total of 114 HT recipients were included (57 assigned to alirocumab and 57 assigned to placebo). Baseline characteristics were well matched between the 2 groups. The low-density lipoprotein cholesterol levels decreased significantly from baseline to 1 year in the alirocumab arm (72.7±31.7 to 31.5±20.7 mg/dL; P <0.001) and did not change with placebo (69.0±22.4 to 69.2±28.1 mg/dL; P =0.92). Plaque volume increased numerically in both groups from baseline to 12 months (alirocumab, 176.3±95.2 to 184.5±105.4 mm³; P =0.23; placebo 173.7±96.7 to 183.1±109.8 mm 3 ; P =0.15). The change in plaque volume (mean difference in differences) did not differ between groups (1.01 [0.89–1.14]; P =0.86). Fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance did not change significantly with the addition of alirocumab. There were no significant adverse events related to alirocumab. CONCLUSIONS: Proprotein convertase subtilisin/kexin 9 inhibition with alirocumab in addition to statin therapy early after HT safely lowers low-density lipoprotein cholesterol but did not reduce coronary artery plaque progression after 1 year compared with rosuvastatin alone in patients with a low baseline low-density lipoprotein cholesterol. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03537742. 35:T813,The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor evolocumab reduces the risk of major adverse cardiovascular events (MACE) among patients with a previous myocardial infarction, stroke, or symptomatic peripheral artery disease. The effect of evolocumab on the risk of MACE among patients without a previous myocardial infarction or stroke is unknown. We conducted an international, double-blind, randomized, placebo-controlled trial of evolocumab in patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke who had a low-density lipoprotein cholesterol level of at least 90 mg per deciliter. Patients were randomly assigned in a 1:1 ratio to receive evolocumab at a dose of 140 mg every 2 weeks or placebo. The two primary end points were a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite of 3-point MACE or ischemia-driven arterial revascularization (4-point MACE). A total of 12,257 patients were randomly assigned to receive evolocumab (6129 patients) or placebo (6128) and were included in the efficacy analyses. The median age of the patients was 66 years, 43% were women, and 93% were White. The median follow-up was 4.6 years. A 3-point MACE event occurred in 336 patients (5-year Kaplan-Meier estimate, 6.2%) in the evolocumab group, as compared with 443 (8.0%) in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). A 4-point MACE event occurred in 747 patients (5-year Kaplan-Meier estimate, 13.4%) in the evolocumab group, as compared with 907 (16.2%) in the placebo group (hazard ratio, 0.81; 95% CI, 0.73 to 0.89; P<0.001). No evidence of a between-group difference was seen in the incidence of safety events. PCSK9 inhibition with evolocumab led to a lower risk of first cardiovascular events than placebo among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke. (Funded by Amgen; VESALIUS-CV ClinicalTrials.gov number, NCT03872401.).36:T530,Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial. The mean LDL-C level was 119.0 mg/dL (SD, 41.0 mg/dL) at baseline, all had statin current use (81.5% were taking a high-intensity statin), and 64.4% were taking ezetimibe. The mean percentage change in LDL-C level at week 24 was -58.2% in the enlicitide group vs 2.6% in the placebo group (between-group difference, -59.4% [95% CI, -65.6% to -53.2%]; P < .001). The mean percentage change in LDL-C level at week 52 was -55.3% in the enlicitide group vs 8.7% in the placebo group (between-group difference, -61.5% [95% CI, -69.4% to -53.7%]; P < .001). At week 24, the mean percentage change in non-HDL-C level was -52.3% in the enlicitide group vs 2.1% in the placebo group (between-group difference, -53.0% [95% CI, -58.5% to -47.4%]; P < .001), the mean percentage change in apolipoprotein B level was -48.2% vs 1.8%, respectively (between-group difference, -49.1% [95% CI, -54.0% to -44.3%]; P < .001), and the median percentage change in lipoprotein(a) level was -24.7% vs -1.6% (between-group difference, -27.5% [95% CI, -34.3% to -20.6%]; P < .001). The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups.37:Tc3d,Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies. To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy. This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least a moderate- or high-intensity statin) and either an LDL-C level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease or an LDL-C level of 70 mg/dL or greater without a history of major atherosclerotic cardiovascular disease. The trial was conducted at 59 sites across 17 countries; the first participant was screened on August 8, 2023, and the last follow-up visit occurred on April 7, 2025. Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks. The primary outcome was the mean percentage change in LDL-C level at week 24. The secondary outcomes included the mean percentage change in LDL-C level at week 52, the mean percentage change at week 24 in levels of non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, and the median percentage change at week 24 in lipoprotein(a). Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial. The mean LDL-C level was 119.0 mg/dL (SD, 41.0 mg/dL) at baseline, all had statin current use (81.5% were taking a high-intensity statin), and 64.4% were taking ezetimibe. The mean percentage change in LDL-C level at week 24 was -58.2% in the enlicitide group vs 2.6% in the placebo group (between-group difference, -59.4% [95% CI, -65.6% to -53.2%]; P < .001). The mean percentage change in LDL-C level at week 52 was -55.3% in the enlicitide group vs 8.7% in the placebo group (between-group difference, -61.5% [95% CI, -69.4% to -53.7%]; P < .001). At week 24, the mean percentage change in non-HDL-C level was -52.3% in the enlicitide group vs 2.1% in the placebo group (between-group difference, -53.0% [95% CI, -58.5% to -47.4%]; P < .001), the mean percentage change in apolipoprotein B level was -48.2% vs 1.8%, respectively (between-group difference, -49.1% [95% CI, -54.0% to -44.3%]; P < .001), and the median percentage change in lipoprotein(a) level was -24.7% vs -1.6% (between-group difference, -27.5% [95% CI, -34.3% to -20.6%]; P < .001). The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups. Among adults with HeFH, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a). ClinicalTrials.gov Identifier: NCT05952869.38:T1416, Importance Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies. Objective To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy. Design, Setting, and Participants This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least a moderate- or high-intensity statin) and either an LDL-C level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease or an LDL-C level of 70 mg/dL or greater without a history of major atherosclerotic cardiovascular disease. The trial was conducted at 59 sites across 17 countries; the first participant was screened on August 8, 2023, and the last follow-up visit occurred on April 7, 2025. Interventions Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks. Main Outcomes and Measures The primary outcome was the mean percentage change in LDL-C level at week 24. The secondary outcomes included the mean percentage change in LDL-C level at week 52, the mean percentage change at week 24 in levels of non–high-density lipoprotein cholesterol (non–HDL-C) and apolipoprotein B, and the median percentage change at week 24 in lipoprotein(a). Results Of the 303 participants (mean age, 52.4 [SD, 13.5] years; 51% were female) randomized, 293 (96.7%) completed the trial. The mean LDL-C level was 119.0 mg/dL (SD, 41.0 mg/dL) at baseline, all had statin current use (81.5% were taking a high-intensity statin), and 64.4% were taking ezetimibe. The mean percentage change in LDL-C level at week 24 was −58.2% in the enlicitide group vs 2.6% in the placebo group (between-group difference, −59.4% [95% CI, −65.6% to −53.2%]; P &lt; .001). The mean percentage change in LDL-C level at week 52 was −55.3% in the enlicitide group vs 8.7% in the placebo group (between-group difference, −61.5% [95% CI, −69.4% to −53.7%]; P &lt; .001). At week 24, the mean percentage change in non–HDL-C level was −52.3% in the enlicitide group vs 2.1% in the placebo group (between-group difference, −53.0% [95% CI, −58.5% to −47.4%]; P &lt; .001), the mean percentage change in apolipoprotein B level was −48.2% vs 1.8%, respectively (between-group difference, −49.1% [95% CI, −54.0% to −44.3%]; P &lt; .001), and the median percentage change in lipoprotein(a) level was −24.7% vs −1.6% (between-group difference, −27.5% [95% CI, −34.3% to −20.6%]; P &lt; .001). The incidence of adverse events, serious adverse events, and study discontinuation due to adverse events was similar between groups. Conclusions Among adults with HeFH, treatment with enlicitide was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non–HDL-C, and lipoprotein(a). Trial Registration ClinicalTrials.gov Identifier: NCT05952869 39:T70e,Patients with previous ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events. The benefits of achieving very low levels of low-density lipoprotein cholesterol (LDL-C) in such patients is unclear. We analyzed patients with previous ischemic stroke enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), a randomized placebo-controlled trial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up, 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up, 5 years), to examine the relationship between achieved LDL-C and the long-term incidence of the primary end point (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization) and stroke-related end points. The analysis included 5291 patients with previous ischemic stroke (>4 weeks). Of these, 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%), and 2121 (40.1%) patients achieved LDL-C values of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. The incidence of the primary end point, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale ( In patients with previous ischemic stroke, it appeared that the lower the LDL-C, down to levels <40 mg/dL, the lower the risk of major adverse cardiovascular events, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke. These findings support the concept that more intensive LDL-C lowering in patients with previous ischemic stroke may be warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01764633/NCT01764633.3a:Tdc3, BACKGROUND: Patients with previous ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events. The benefits of achieving very low levels of low-density lipoprotein cholesterol (LDL-C) in such patients is unclear. METHODS: We analyzed patients with previous ischemic stroke enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), a randomized placebo-controlled trial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up, 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up, 5 years), to examine the relationship between achieved LDL-C and the long-term incidence of the primary end point (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization) and stroke-related end points. RESULTS: The analysis included 5291 patients with previous ischemic stroke (>4 weeks). Of these, 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%), and 2121 (40.1%) patients achieved LDL-C values of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. The incidence of the primary end point, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale ( P trend <0.001, 0.002, and 0.002, respectively). Compared with patients with LDL-C ≥70 mg/dL, those who achieved levels <40 mg/dL had incidence rate ratios of 0.69 (95% CI, 0.57–0.84), 0.73 (95% CI, 0.53–0.99), and 0.75 (95% CI, 0.54–1.05) for the outcomes of the primary end point, all stroke, and ischemic stroke, respectively. Hemorrhagic strokes were infrequent and unrelated to achieved LDL-C ( P trend =0.85). CONCLUSIONS: In patients with previous ischemic stroke, it appeared that the lower the LDL-C, down to levels <40 mg/dL, the lower the risk of major adverse cardiovascular events, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke. These findings support the concept that more intensive LDL-C lowering in patients with previous ischemic stroke may be warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01764633/NCT01764633. 3b:T7c5,Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding. To investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk. This 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance-weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses. Genetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker. Risk of psoriasis. Data from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition. This mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.3c:Tab6,ImportanceLipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding.ObjectiveTo investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk.Design, Setting, and ParticipantsThis 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance–weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses.ExposuresGenetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1–like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker.Main Outcomes and MeasuresRisk of psoriasis.ResultsData from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition.Conclusions and RelevanceThis mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"PCSK9 Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on PCSK9 Inhibitor (modality). Clinician-written summaries and actionable practice insights. 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CV death HR was 0.79 (95% CI 0.64–0.98); non-CV death HR was 0.85 (95% CI 0.71–1.01). Multistate modeling suggested ~78% of the non-CV mortality benefit was mediated through prevention of antecedent nonfatal CV events (MI, ischemic stroke, or revascularization).","limitations":"- Non-CV death reduction did not reach statistical significance (HR 0.85; CI crossed 1.0).\n- Causal mediation via multistate modeling is observational in nature and cannot definitively establish mechanistic pathways.\n- Median follow-up of 4.6 years may underestimate long-term survival benefit.","practice_takeaway":"Evolocumab reduced all-cause mortality by 20% in high-risk patients without prior MI or stroke, including those with high-risk diabetes and LDL-C ≥90 mg/dL — a population often undertreated with PCSK9 inhibitors. Clinicians should consider evolocumab for survival benefit, not just event prevention, in this primary-prevention-adjacent group."}},{"doi":"10.1001/jamacardio.2026.2314","pmid":"42455545","title":"Development and Validation of a Simplified Martin-Hopkins LDL-C Equation Using Machine Learning","journal_title":"JAMA Cardiology","journal_issn":"2380-6583","published_at":"2026-07-15T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13373734/","source_score":52,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-19T13:39:49.482Z","updated_at":"2026-07-19T13:39:49.482Z","tags":[{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"LDL-C Estimation Equation","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"Machine Learning","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"sample_size","value":"n=4939528","value_numeric":4939528},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"Full text of the paper was not accessible (publisher page only); summary is based solely on the abstract and results section provided.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"The MARS equation is described as a 'single equation' simplification, but its machine learning nature may still require computational implementation — manual bedside use is not confirmed in the abstract.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"The study is cross-sectional, so the 'level of evidence' rating reflects diagnostic/accuracy study hierarchy rather than an interventional hierarchy.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study developed and validated a simplified machine learning-based LDL-C estimation equation (LDL-C-MH-MARS, using multivariate adaptive regression splines) as an alternative to the Martin-Hopkins equation, comparing it against the Friedewald, Sampson-NIH, Modified Sampson, and Martin-Hopkins equations in ~4.9 million adult and pediatric patients from the Very Large Database of Lipids (2015–2019), with external validation in Mayo Clinic and FOURIER trial datasets.","key_result":"LDL-C-MH-MARS achieved the lowest RMSE (4.7 mg/dL vs. 4.9 for Martin-Hopkins, 5.8 for Sampson-NIH, and 7.2 for Friedewald) and correctly classified 89.7% of patients by guideline category (vs. 89.6% for Martin-Hopkins and 83.1% for Friedewald); at low LDL-C (<70 mg/dL) with elevated triglycerides (200–399 mg/dL), underestimation occurred in only 16% with MARS vs. 60% with Friedewald.","limitations":"- Cross-sectional convenience sample may not fully represent all clinical populations.\n- LDL-C reference standard was ultracentrifugation, which itself has known variability.\n- The MARS equation may be harder to implement manually than simpler formulas, despite being a single equation.","practice_takeaway":"The new LDL-C-MH-MARS equation matches the accuracy of the Martin-Hopkins method while using a single equation, making it easier to embed in lab or EHR systems—especially useful for patients with elevated triglycerides or low LDL-C where Friedewald significantly underestimates. Clinicians managing high-risk patients on intensive lipid-lowering therapy (e.g., PCSK9 inhibitors) should prefer MARS or Martin-Hopkins over Friedewald for LDL-C estimation."}},{"doi":"10.1016/s2213-8587(26)00102-6","pmid":"42259344","title":"A quarter-century of progress: innovations in lipid medicine that transformed cardiovascular prevention","journal_title":"The Lancet Diabetes & Endocrinology","journal_issn":"2213-8587","published_at":"2026-06-08T00:00:00.000Z","url":"https://doi.org/10.1016/s2213-8587(26)00102-6","source_score":16,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-16T13:54:30.429Z","updated_at":"2026-06-16T13:54:30.429Z","tags":[{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"condition","value":"Dyslipidemia","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"generic","value":"inclisiran","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"generic","value":"olpasiran","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"modality","value":"DNA-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"modality","value":"RNA-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"warning","value":"Specific drugs highlighted (e.g., olpasiran, inclisiran) are mentioned illustratively within the review context; individual trial data should be consulted for efficacy and safety estimates.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"warning","value":"The review discusses AI applications in lipid medicine, but this is described as emerging/prospective — no clinical outcomes data for AI-guided management are provided.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00102-6","tag_type":"warning","value":"This is a narrative TimeCapsule review, not a systematic review or meta-analysis; no original data or pooled effect sizes are reported.","value_numeric":null}],"summaries":{"what_studied":"This TimeCapsule review covers 25 years (early 21st century) of advances in lipid medicine and cardiovascular prevention, tracing the evolution from statin-centric care to RNA/DNA-targeted therapies and emerging AI-driven approaches.","key_result":"Statins remain foundational, but non-statin agents (PCSK9 inhibitors, inclisiran, olpasiran, etc.) and RNA/DNA-targeted therapies modulating PCSK9, Lp(a), ApoC-III, and ANGPTL3 have expanded the prevention toolkit; the core paradigm—earlier and sustained LDL-C lowering yields greater cardiovascular risk reduction—is firmly established, yet the proportion of patients meeting guideline targets remains unacceptably low.","limitations":"As a narrative TimeCapsule review, it does not synthesize original trial data or perform meta-analysis, limiting its ability to quantify effect sizes or directly compare interventions; evidence-practice gap is noted but not quantified.","practice_takeaway":"Prioritize earlier and sustained LDL-C lowering using statins plus non-statin therapies (e.g., PCSK9 inhibitors, RNA-targeted agents) for high-risk patients, and integrate newer risk metrics—ApoB, non-HDL-C, Lp(a), remnant cholesterol—into residual risk assessment. Awareness of sex-specific cardiovascular risk differences should inform individualized prevention strategies."}},{"doi":"10.2337/dc26-0847","pmid":"42251764","title":"Evolocumab in Patients With High-Risk Diabetes: Results From the VESALIUS-CV Trial","journal_title":"Diabetes Care","journal_issn":"0149-5992","published_at":"2026-06-07T00:00:00.000Z","url":"https://doi.org/10.2337/dc26-0847","source_score":45,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:37.091Z","updated_at":"2026-06-12T13:24:37.091Z","tags":[{"paper_doi":"10.2337/dc26-0847","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"condition","value":"Dyslipidemia","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"sample_size","value":"n=6002","value_numeric":6002},{"paper_doi":"10.2337/dc26-0847","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"warning","value":"A typographical error ('porportion') was noted in the source abstract but has no bearing on data interpretation.","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"warning","value":"Level of evidence tagged as 2 (prespecified subgroup of an RCT) rather than 1, given the subgroup nature of this analysis.","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"warning","value":"The paper is very recently published (June 7, 2026); full peer-reviewed supplementary data may not yet be widely available.","value_numeric":null},{"paper_doi":"10.2337/dc26-0847","tag_type":"warning","value":"This is a prespecified subgroup analysis of the VESALIUS-CV trial, not an independent RCT; the overall trial enrolled patients with qualifying atherosclerosis as well, so results apply specifically to the 6,002 diabetes subgroup. The full trial sample size is larger than reported here.","value_numeric":null}],"summaries":{"what_studied":"Prespecified subgroup analysis of the VESALIUS-CV RCT evaluating evolocumab 140 mg SC every 2 weeks vs. placebo in 6,002 patients with high-risk diabetes (microvascular disease, insulin use, or duration ≥10 years) but **no prior MI or stroke**, with LDL-C ≥90 mg/dL, over a median follow-up of 4.6 years.","key_result":"Evolocumab reduced 3P-MACE by 29% (HR 0.71; 95% CI 0.59–0.86; P = 0.0004) and 4P-MACE by 21% (HR 0.79; 95% CI 0.69–0.91; P = 0.0013). All-cause death was 8.8% vs. 11.0% (HR 0.79; 95% CI 0.67–0.93). Median LDL-C at 48 weeks was 47 mg/dL (evolocumab) vs. 109 mg/dL (placebo). Benefits were consistent regardless of baseline atherosclerosis, LDL-C, statin intensity, or SGLT2i/GLP-1RA use.","limitations":"- This is a prespecified *subgroup* analysis of VESALIUS-CV, not the primary trial; absolute event rates for the diabetes subgroup alone are not fully reported.\n- Only 24% of patients were on an SGLT2i or GLP-1RA, limiting generalizability to contemporary diabetes management.\n- The trial excluded patients with prior MI or stroke, so findings may not apply to secondary prevention populations.","practice_takeaway":"For patients with high-risk diabetes and no prior MI or stroke who remain above LDL-C goals despite statins, adding evolocumab meaningfully cuts MACE and all-cause death — even when SGLT2i or GLP-1RA are already on board. Clinicians should consider PCSK9 inhibition as part of primary prevention in this high-risk group."}},{"doi":"10.1111/dom.70944","pmid":"42244216","title":"Comparative Effects of Emerging Lp(a)‐Lowering Agents and\n PCSK9\n ‐Directed Therapies on Lipoprotein(a): A Network Meta‐Analysis of Randomised Clinical Trials","journal_title":"Diabetes, Obesity and Metabolism","journal_issn":"1462-8902","published_at":"2026-06-04T00:00:00.000Z","url":"https://doi.org/10.1111/dom.70944","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-09T13:50:35.173Z","updated_at":"2026-06-09T13:50:35.173Z","tags":[{"paper_doi":"10.1111/dom.70944","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"brand","value":"Praluent","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"condition","value":"Elevated Lipoprotein(a)","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"alirocumab","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"lepodisiran","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"muvalaplin","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"olpasiran","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"pelacarsen","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"generic","value":"zerlasiran","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"modality","value":"Antisense Oligonucleotide","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"modality","value":"Oral Assembly Inhibitor","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"modality","value":"Small Interfering RNA (siRNA)","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"sample_size","value":"n=17810","value_numeric":17810},{"paper_doi":"10.1111/dom.70944","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"study_design","value":"Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"warning","value":"High heterogeneity (I² = 90.9%) and funnel plot asymmetry substantially reduce certainty for individual treatment estimates; rankings should be interpreted directionally rather than as precise comparisons.","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"warning","value":"Most Lp(a)-targeted agents (olpasiran, zerlasiran, lepodisiran, muvalaplin) lack completed cardiovascular outcome trials; clinical benefit is inferred from Lp(a) reduction, not hard endpoints.","value_numeric":null},{"paper_doi":"10.1111/dom.70944","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the scale of Lp(a) reductions demonstrated, but should be viewed cautiously given the absence of outcomes data for emerging agents.","value_numeric":null}],"summaries":{"what_studied":"This network meta-analysis compared the efficacy and safety of emerging Lp(a)-targeted therapies (siRNAs: olpasiran, zerlasiran, lepodisiran; antisense oligonucleotide: pelacarsen; oral assembly inhibitor: muvalaplin) versus PCSK9-directed therapies (evolocumab, alirocumab) on percent change in Lp(a) from baseline across 51 RCTs (n=17,810 adults, ≥8-week follow-up) through December 2025.","key_result":"Olpasiran 225 mg Q12W showed the greatest Lp(a) reduction (MD −98.94 pp vs. placebo, 95% CI −114.36 to −83.52); pelacarsen, muvalaplin, zerlasiran, and lepodisiran also produced large reductions. PCSK9 inhibitors offered more modest Lp(a) lowering (evolocumab 140 mg Q2W: MD −31.58 pp) but greater LDL-C reduction. No agent was linked to more serious adverse events or discontinuations versus placebo; alirocumab 150 mg had more injection-site reactions.","limitations":"- Very high heterogeneity (I² = 90.9%) in the primary Lp(a) network, limiting confidence in point estimates.\n- Funnel plot asymmetry suggests possible publication bias or small-study effects.\n- No cardiovascular outcome trial data yet available for most Lp(a)-targeted agents, so clinical hard-endpoint benefit remains unproven.","practice_takeaway":"Emerging Lp(a)-specific agents (especially olpasiran, zerlasiran, lepodisiran, pelacarsen, muvalaplin) cut Lp(a) far more than PCSK9 inhibitors, but cardiovascular outcome trials are still needed before routine use. PCSK9 inhibitors remain the better choice when both LDL-C and Lp(a) lowering are priorities."}},{"doi":"10.1167/tvst.15.5.29","pmid":"42212887","title":"Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration","journal_title":"Translational Vision Science & Technology","journal_issn":"2164-2591","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1167/tvst.15.5.29","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:39.163Z","updated_at":"2026-06-03T13:44:39.163Z","tags":[{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Leqvio","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Praluent","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"condition","value":"Age-Related Macular Degeneration","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"alirocumab","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"inclisiran","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"sample_size","value":"n=56660","value_numeric":56660},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"AMD subtype (wet vs. dry/geographic atrophy) could not be distinguished due to ICD-10-code-only outcome ascertainment; results apply to AMD overall.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Brand tags (Praluent, Repatha, Leqvio) are inferred from the generic drug names listed; the paper does not explicitly name brand products.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Follow-up duration differed between groups (mean ~1037 days for PCSK9i vs. ~1317 days for statins), which may affect cumulative incidence comparisons despite Cox modeling.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Propensity score matching balanced measured covariates, but PCSK9 inhibitor users likely had more severe dyslipidemia or statin intolerance at baseline—confounding by indication may persist.","value_numeric":null}],"summaries":{"what_studied":"This retrospective propensity score–matched cohort study (TriNetX database, 2015–2024, up to 5 years follow-up) compared incident AMD risk in adults ≥50 years with hyperlipidemia who used PCSK9 inhibitors (alirocumab, evolocumab, or inclisiran) versus statin monotherapy, with no prior retinal disease at baseline.","key_result":"Among 56,660 matched participants (28,330 per group), PCSK9 inhibitor use was associated with a significantly lower AMD risk vs. statins (HR 0.82; 95% CI 0.73–0.90). The benefit was consistent in sensitivity analyses (US-only network: HR 0.85; intention-to-treat: HR 0.87) and in subgroups including both age groups (50–75 yrs: HR 0.83; ≥75 yrs: HR 0.84), males (HR 0.82), non-diabetic individuals (HR 0.79), non-obese individuals (HR 0.70), and those with <2 years of hyperlipidemia (HR 0.81). No significant benefit was seen in those with ≥2 years of hyperlipidemia (HR 0.92; 95% CI 0.83–1.02).","limitations":"- AMD diagnosis relied solely on ICD-10-CM codes (no fundus imaging, visual acuity, or drusen data), with ~80–85% accuracy vs. image-derived ground truth.\n- Confounding by indication is likely: PCSK9 inhibitors are typically reserved for more severe dyslipidemia or statin-intolerant patients, which may not be fully captured even after propensity matching.\n- Residual confounding from unmeasured factors (diet, genetics, supplement use) cannot be excluded, and the observational design precludes causal inference.","practice_takeaway":"In adults ≥50 years on lipid-lowering therapy, PCSK9 inhibitor use was linked to an 18% relative reduction in AMD risk vs. statins—a finding that may inform treatment discussions, especially in patients already requiring PCSK9 inhibition for cardiovascular reasons. Causal confirmation requires prospective trials with standardized ophthalmic endpoints."}},{"doi":"10.1503/cmaj.251137-f","pmid":"42185004","title":"Prise en charge de la multimorbidité cœur–cerveau : un guide de pratique clinique","journal_title":"Canadian Medical Association Journal","journal_issn":"0820-3946","published_at":"2026-05-24T00:00:00.000Z","url":"https://doi.org/10.1503/cmaj.251137-f","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-06T13:22:59.649Z","updated_at":"2026-06-06T13:22:59.649Z","tags":[{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Atrial Fibrillation","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Coronary Artery Disease","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Dyslipidemia","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Heart-Brain Multimorbidity","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Myocardial Infarction","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"condition","value":"Stroke","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Antihypertensive Therapy","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Cognitive Behavioural Therapy","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Herpes Zoster Vaccine","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Influenza Vaccine","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Pneumococcal Vaccine","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"SSRI","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"warning","value":"Evidence for vaccination and dementia outcomes is largely observational; recommendations on shingles vaccine and dementia are downgraded to level 3, grade C.","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"warning","value":"No sample size tag was applied: this is a guideline synthesizing multiple studies rather than a single primary study with one N.","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"warning","value":"Recommendations on behavioral interventions and diabetes–heart–brain comorbidity were not finalized due to insufficient evidence or failure to reach consensus threshold at time of publication.","value_numeric":null},{"paper_doi":"10.1503/cmaj.251137-f","tag_type":"warning","value":"This is a French-language translation of the original English guideline published March 30, 2026 (CMAJ 198:E425-39); the canonical citation should reference the English version.","value_numeric":null}],"summaries":{"what_studied":"This C-CHANGE clinical practice guideline evaluated the screening and management of concurrent heart–brain multimorbidity (atrial fibrillation + cognitive impairment, coronary artery disease + depression, hypertension + cognitive impairment, dyslipidemia + stroke risk, and vaccination for prevention of stroke/MI/dementia) primarily for primary care providers. Evidence was synthesized from systematic reviews, meta-analyses, and RCTs published up to August 2024.","key_result":"Eleven recommendations were issued: **Screen** patients with AF for cognitive decline (evidence level 2A, grade B) and CAD patients for depression (1B, grade B). **Treat** confirmed depression in CAD with SSRIs (1A, grade A) or CBT (1B, grade C); target systolic BP <120 mmHg in hypertensive patients at high CV risk to reduce cognitive impairment risk (1B, grade A); intensify LDL-lowering to <1.8 mmol/L in CAD (1A, grade A) and post-stroke (1B, grade B). **Vaccinate** routinely—especially those ≥65 years—against influenza (reduces CV death by 23–47%, stroke by 13–19%), pneumococcus (reduces MI RR 0.88, stroke RR 0.86–0.90), and shingles (reduces stroke OR 0.78, MI OR 0.63–0.73). Shared decision-making using evidence-based decision aids is also recommended (1A, grade B).","limitations":"- Most included studies were not designed to assess joint heart–brain outcomes directly, leading to evidence downgrading for nearly all recommendations.\n- Women and sex/gender-specific analyses were markedly underrepresented across the underlying trials (e.g., men comprised 75–83% of lipid-lowering trial participants).\n- Scope is intentionally narrow; many heart–brain comorbidity combinations (e.g., heart failure + cognition, diabetes + heart–brain disease, RSV/COVID-19 vaccination) lacked sufficient evidence for formal recommendations.","practice_takeaway":"Clinicians managing patients with AF, CAD, hypertension, dyslipidemia, or stroke should routinely screen for cognitive decline and depression, treat both cardiac and mental health conditions together, and proactively offer influenza, pneumococcal, and shingles vaccines to reduce downstream CV and dementia risk. Shared decision-making tools should be integrated into consultations to align care with patient values."}},{"doi":"10.1161/circulationaha.126.080616","pmid":"42153665","title":"Evolocumab in Patients With Prior Percutaneous Coronary Intervention and No Prior Myocardial Infarction: Results From the VESALIUS-CV Trial","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-05-19T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.080616","source_score":41,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-07T13:26:26.620Z","updated_at":"2026-07-07T13:26:26.620Z","tags":[{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"condition","value":"Coronary Artery Disease","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"sample_size","value":"n=3627","value_numeric":3627},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"Cardiovascular death and all-cause death reductions are described as 'nominally' significant, suggesting these were not primary endpoints and may not be adjusted for multiple comparisons.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"Median age of 66 years with 30.7% women; generalizability to younger or predominantly female PCI populations is uncertain.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"This is a prespecified subgroup analysis (n=3,627) from the larger VESALIUS-CV trial (n=12,257); results should be interpreted with caution as the subgroup was not independently powered.","value_numeric":null}],"summaries":{"what_studied":"This prespecified subgroup analysis of the VESALIUS-CV RCT evaluated evolocumab vs. placebo in 3,627 patients with prior PCI but no prior MI or stroke, with LDL-C ≥90 mg/dL, over a median follow-up of 4.6 years.","key_result":"Evolocumab reduced 3-point MACE by 30% (7.0% vs. 9.5%; HR 0.70, 95% CI 0.56–0.89), MI by 50% (3.0% vs. 6.1%; HR 0.50), and urgent revascularization by 39% (HR 0.61); nominally lower all-cause death (8.2% vs. 10.2%; HR 0.76) was also observed. Benefit appeared as early as 6 months.","limitations":"- Subgroup analysis, so not powered independently for these endpoints.\n- LDL-C data at 48 weeks came from a lipid substudy, not the full cohort.\n- Death and cardiovascular death findings are described as 'nominally' significant, suggesting no formal multiplicity correction was applied.","practice_takeaway":"Consider adding evolocumab to stable post-PCI patients without prior MI who remain at LDL-C ≥90 mg/dL, as intensive LDL-C lowering cut MI risk in half and reduced major cardiovascular events meaningfully. Benefit appeared within 6 months, supporting early initiation."}},{"doi":"10.1016/j.jacc.2026.03.036","pmid":"42017875","title":"Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies","journal_title":"JACC","journal_issn":"0735-1097","published_at":"2026-03-30T00:00:00.000Z","url":"https://doi.org/10.1016/j.jacc.2026.03.036","source_score":161,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-26T13:44:37.390Z","updated_at":"2026-07-26T13:44:37.390Z","tags":[{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"brand","value":"Nexlizet","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"condition","value":"Hypercholesterolemia","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"generic","value":"bempedoic acid","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"generic","value":"enlicitide","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"generic","value":"ezetimibe","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"modality","value":"ATP-Citrate Lyase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"modality","value":"Cholesterol Absorption Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"sample_size","value":"n=301","value_numeric":301},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"warning","value":"Bempedoic acid showed only a 6.3% LDL-C reduction, which is lower than typically reported; the patient population (already on moderate-to-high intensity statins) may partially explain this attenuated response.","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"warning","value":"The 'practice_changing' flag reflects the novelty of an oral PCSK9 inhibitor with this magnitude of LDL-C reduction, but enlicitide is not yet approved as of the study publication date; clinical impact depends on regulatory decisions.","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.03.036","tag_type":"warning","value":"Trial duration was only 56 days — no long-term safety or cardiovascular outcomes data are available for enlicitide from this study.","value_numeric":null}],"summaries":{"what_studied":"Phase 3 randomized double-blind active-comparator trial evaluating enlicitide (oral PCSK9 inhibitor, 20 mg) vs bempedoic acid (180 mg), ezetimibe (10 mg), or bempedoic acid + ezetimibe (180/10 mg) once daily for 56 days in statin-treated adults (≥18 years) with LDL-C ≥55 mg/dL and prior major ASCVD event, or LDL-C ≥70 mg/dL at intermediate-to-high risk for a first event (n=301).","key_result":"Enlicitide reduced LDL-C by **64.6%** from baseline vs **6.3%** with bempedoic acid, **27.8%** with ezetimibe, and **36.5%** with bempedoic acid + ezetimibe (all P < 0.001); reductions in ApoB and non-HDL-C were also significantly greater with enlicitide, and adverse event rates were similar across all arms.","limitations":"- Short trial duration (56 days) limits conclusions about long-term efficacy and safety.\n- No cardiovascular outcomes data; LDL-C reduction is a surrogate endpoint.\n- Relatively small sample size per arm (n=50–101), reducing power to detect rare adverse events.","practice_takeaway":"For statin-treated patients who remain above LDL-C goals, oral enlicitide achieves far greater LDL-C lowering (~65%) than ezetimibe or bempedoic acid with a comparable short-term safety profile. Clinicians managing high-risk patients who cannot use injectable PCSK9 inhibitors may consider enlicitide as a potent oral add-on once it is approved."}},{"doi":"10.1001/jama.2026.3277","pmid":"41903215","title":"Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes","journal_title":"JAMA","journal_issn":"0098-7484","published_at":"2026-03-29T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13033171/","source_score":427,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-01","doi":"10.1001/jama.2026.3277","days":"14","issn":"0098-7484","rank":"9","field":"Clinical Medicine","score":"427","category":"Medicine, General & Internal","categories":["Medicine, General & Internal"],"_categories":["Medicine, General & Internal"]},"pubmed":{"doi":"10.1001/jama.2026.3277","title":"Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant 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It also cut 4-P MACE by 31% (7.6% vs 10.5%; HR 0.69 [95% CI 0.55–0.86]; absolute difference 2.9%) and showed a mortality signal (7.8% vs 10.1%; HR 0.76 [95% CI 0.61–0.95]). Median LDL-C at 48 weeks was 52 mg/dL (evolocumab) vs 111 mg/dL (placebo).","limitations":"- This is a **prespecified subgroup** of the main VESALIUS-CV trial, so statistical power was designed for the overall cohort, not this subgroup alone.\n- All patients in this subgroup had diabetes, limiting generalizability to non-diabetic patients without significant atherosclerosis.\n- Full-text safety and tolerability data were not accessible from the available abstract.","practice_takeaway":"Consider evolocumab as a primary prevention option in patients with diabetes and elevated LDL-C (≥90 mg/dL) who lack known significant atherosclerosis — a population previously excluded from routine PCSK9 inhibitor use. A 2.1% absolute reduction in 3-P MACE over ~5 years translates to roughly 1 event prevented per 48 patients treated."}},{"doi":"10.1161/circulationaha.125.077603","pmid":"41212178","title":"Cardiac Allograft Vasculopathy Inhibition With Alirocumab: The CAVIAR Trial","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2025-11-10T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.125.077603","source_score":47,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-11","doi":"10.1161/circulationaha.125.077603","days":"14","issn":"0009-7322","rank":"7","field":"Clinical Medicine","score":"47","category":"Cardiac & Cardiovascular Systems","categories":["Cardiac & Cardiovascular Systems"],"_categories":["Cardiac & Cardiovascular Systems"]},"pubmed":{"doi":"10.1161/CIRCULATIONAHA.125.077603","title":"Cardiac Allograft Vasculopathy Inhibition With Alirocumab: The CAVIAR Trial.","journal":"Circulation","methods":"","results":"A total of 114 HT recipients were included (57 assigned to alirocumab and 57 assigned to placebo). 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The primary outcome was mean percentage change in LDL-C at week 24.","key_result":"LDL-C fell by a mean of −58.2% with enlicitide vs +2.6% with placebo at week 24 (between-group difference −59.4% [95% CI, −65.6% to −53.2%]; P<.001) and by −55.3% vs +8.7% at week 52 (difference −61.5% [95% CI, −69.4% to −53.7%]; P<.001). At week 24, non-HDL-C fell −52.3% vs +2.1% (difference −53.0% [95% CI, −58.5% to −47.4%]), apolipoprotein B −48.2% vs +1.8% (difference −49.1% [95% CI, −54.0% to −44.3%]), and lipoprotein(a) median −24.7% vs −1.6% (difference −27.5% [95% CI, −34.3% to −20.6%]); adverse event rates were similar between groups.","limitations":"Outcomes were lipid changes over 24–52 weeks; no cardiovascular event data were reported. Safety was described as similar without event counts, and durability beyond 52 weeks is unknown.","practice_takeaway":"In adults with HeFH on statins who need additional LDL lowering, oral enlicitide produced large, sustained reductions in LDL-C and other atherogenic lipids over 52 weeks with similar adverse events to placebo. It may serve as a potent oral add-on when further LDL reduction is required."}},{"doi":"10.1161/circulationaha.125.077549","pmid":"41178569","title":"Efficacy and Safety of Very Low Achieved LDL Cholesterol in Patients With Previous Ischemic Stroke","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2025-11-03T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.125.077549","source_score":52,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-17","doi":"10.1161/circulationaha.125.077549","days":"7","issn":"0009-7322","rank":"10","field":"Clinical Medicine","score":"52","category":"Cardiac & Cardiovascular Systems","categories":["Cardiac & Cardiovascular Systems"],"_categories":["Cardiac & Cardiovascular Systems"]},"pubmed":{"doi":"10.1161/CIRCULATIONAHA.125.077549","title":"Efficacy and Safety of Very Low Achieved LDL Cholesterol in Patients With Previous Ischemic Stroke.","journal":"Circulation","methods":"","results":"The analysis included 5291 patients with previous ischemic stroke (>4 weeks). 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for the primary composite, all stroke, and ischemic stroke decreased monotonically with lower achieved LDL‑C on a continuous scale, down to <40 mg/dL, without a clear increase in hemorrhagic stroke.","practice_takeaway":"In ischemic stroke survivors, achieving very low LDL‑C (down to <40 mg/dL) was associated with fewer major cardiovascular events and recurrent stroke without an apparent increase in hemorrhagic stroke, supporting intensive LDL‑C lowering in this population."}},{"doi":"10.1001/jamadermatol.2022.6051","pmid":"36696131","title":"Association of Lipid-Lowering Drugs With Risk of Psoriasis","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2023-01-26T00:00:00.000Z","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9878432","source_score":41,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2023-02-03","doi":"10.1001/jamadermatol.2022.6051","days":"30","issn":"2168-6068","rank":"3","field":"Clinical 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Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition.","abstract":"$3b","keywords":[],"pubmed_id":"36696131","conclusions":"","publication_date":"2023-01-26T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2022.6051","URL":"https://doi.org/10.1001/jamadermatol.2022.6051","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2800634/jamadermatology_zhao_2023_oi_220068_1677862995.84121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"275","type":"journal-article","issue":"3","score":1,"title":["Association of Lipid-Lowering Drugs With Risk of Psoriasis"],"author":[{"given":"Sizheng Steven","family":"Zhao","sequence":"first","affiliation":[{"name":"Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, England"}]},{"given":"Zenas Z. N.","family":"Yiu","sequence":"additional","affiliation":[{"name":"Centre for Dermatology Research, Salford Royal National Health Service Foundation Trust, National Institute for Health and Care Research Manchester Biomedical Research Centre, University of Manchester, Manchester, England"}]},{"given":"Anne","family":"Barton","sequence":"additional","affiliation":[{"name":"Centre for Genetics and Genomics Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, England"}]},{"given":"John","family":"Bowes","sequence":"additional","affiliation":[{"name":"Centre for Genetics and Genomics Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, 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Data included 12,116 psoriasis cases and about 1.3 million individuals with LDL measures.","key_result":"Genetically proxied PCSK9 inhibition was linked to lower psoriasis risk: OR 0.69 per SD reduction in LDL (95% CI 0.55-0.88; P=.003) with replication in FinnGen (OR 0.71; 95% CI 0.57-0.88; P=.002). Sensitivity analyses did not show statistical evidence of pleiotropy or genetic confounding; no robust association was found for HMGCR or NPC1L1 inhibition."}}],"initialOffset":15,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"PCSK9 Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"PCSK9 Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"PCSK9 Inhibitor"}}}]]

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