Chi-Hsien Huang, Shiow-Ing Wang, Frank S Fan, Hsueh-Ju Lu, James Cheng-Chung Wei
{"title":"Association of PCSK9 inhibitors with mortality: insights from a retrospective cohort analysis.","authors":"Chi-Hsien Huang, Shiow-Ing Wang, Frank S Fan, Hsueh-Ju Lu, James Cheng-Chung Wei","doi":"10.1093/ehjcvp/pvae056","DOIUrl":"10.1093/ehjcvp/pvae056","url":null,"abstract":"<p><strong>Aims: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in reducing cardiovascular events, but their impact on all-cause mortality and medical utilization compared to statins is unclear. This study investigated PCSK9 inhibitor use and its impact on mortality and medical utilization vs. statins, using TriNetX database data with up to 9 years of follow-up.</p><p><strong>Methods and results: </strong>This retrospective cohort study analysed TriNetX data spanning 1 July 2015, to 31 December 2023, including 79 194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5 437 513 statin users with hyperlipidaemia. The primary outcomes were all-cause mortality and medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation. Propensity score matching showed that PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.717, 95% confidence interval (CI): 0.673-0.763] and significant reductions in medical utilization (hospital inpatient services usage: aHR 0.692, 95% CI: 0.664-0.721; emergency department services: aHR 0.756, 95% CI: 0.726-0.788; critical care services: aHR 0.619, 95% CI: 0.578-0.664; and mechanical ventilation: aHR 0.537, 95% CI: 0.484-0.596) compared to statins. These findings were consistent across various demographics and clinical subgroups. The sensitivity analyses supported the robustness of the findings.</p><p><strong>Conclusion: </strong>PCSK9 inhibitors significantly reduced all-cause mortality and medical utilization compared to statins, suggesting their important role in dyslipidaemia management, particularly for statin-naïve or intolerant patients. Further research, including randomized controlled trials, is needed to confirm these findings and explore the underlying mechanisms.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"505-514"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pascal M Burger, Deepak L Bhatt, Jannick A N Dorresteijn, Stefan Koudstaal, Arend Mosterd, Fabrice M A C Martens, Philippe Gabriel Steg, Frank L J Visseren
{"title":"Effects of icosapent ethyl according to baseline residual risk in patients with atherosclerotic cardiovascular disease: results from REDUCE-IT.","authors":"Pascal M Burger, Deepak L Bhatt, Jannick A N Dorresteijn, Stefan Koudstaal, Arend Mosterd, Fabrice M A C Martens, Philippe Gabriel Steg, Frank L J Visseren","doi":"10.1093/ehjcvp/pvae030","DOIUrl":"10.1093/ehjcvp/pvae030","url":null,"abstract":"<p><strong>Aims: </strong>Icosapent ethyl lowers triglycerides and significantly reduces major adverse cardiovascular events (MACE), though treatment effects may vary between individuals. This study aimed to determine the relative and absolute effects of icosapent ethyl on MACE according to baseline cardiovascular disease (CVD) risk in patients with atherosclerotic cardiovascular disease (ASCVD).</p><p><strong>Methods and results: </strong>Participants from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with ASCVD were included (n = 5785). The primary outcome was 3-point MACE, i.e. non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. Baseline 5-year risk of MACE was estimated using the European Society of Cardiology (ESC) guideline-recommended SMART2 risk score. Modification of the relative treatment effects of icosapent ethyl by baseline risk was assessed using Cox proportional hazards models, including a treatment-by-risk interaction. Next, treatment effects were assessed stratified by quartiles of baseline risk. During a median follow-up of 4.8 years (interquartile range 3.2-5.3), MACE occurred in 361 vs. 489 patients in the icosapent ethyl vs. placebo group [95% confidence interval (CI)]; hazard ratio (HR) 0.72 (0.63-0.82), absolute risk reduction (ARR) 4.4% (2.6-6.2%), number needed to treat (NNT) 23 (16-38), and 5-year Kaplan-Meier estimated cumulative incidence reduction (CIR) 5.7% (3.5-7.9%). Icosapent ethyl significantly reduced MACE in all risk quartiles, with an HR (95% CI) of 0.62 (0.43-0.88), 0.66 (0.48-0.92), 0.69 (0.53-0.90), and 0.78 (0.63-0.96), respectively (P for treatment-by-risk interaction = 0.106). The ARR (95% CI) increased across risk quartiles, i.e. was 3.9% (1.0-6.8%), 4.3% (1.2-7.3%), 5.1% (1.4-8.7%), and 5.6% (1.3-10.0%), respectively. This translates to NNTs (95% CI) of 26 (15-98), 24 (14-84), 20 (11-70), and 18 (10-77). The 5-year CIR (95% CI) was 4.8% (1.3-8.2%), 5.0% (1.3-8.7%), 6.1% (1.7-10.5%), and 7.7% (2.3-13.2%), respectively. Consistent results were obtained for 5-point MACE, additionally including coronary revascularization and unstable angina.</p><p><strong>Conclusion: </strong>Among patients with ASCVD and elevated triglyceride levels, icosapent ethyl significantly reduces the risk of MACE irrespective of baseline CVD risk, though absolute benefits are largest for patients at the highest risk.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"488-499"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study.","authors":"Bohan Fan, Jie V Zhao","doi":"10.1093/ehjcvp/pvae038","DOIUrl":"10.1093/ehjcvp/pvae038","url":null,"abstract":"<p><strong>Background: </strong>Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear.</p><p><strong>Methods and results: </strong>To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug-target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis, and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan. After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs), and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78-3.28 per 5 mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47-5.33, and vasodilators: 2.92, 95% CI 1.08-4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan, with CPT2 further supported by colocalization evidence. Eighty-six proteins were related to lifespan, of which four proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan.</p><p><strong>Conclusions: </strong>Beta-blockers, CCBs, and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"537-546"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anton Pottegård, Lars Ulrik Gerdes, Jakob Langballe Wetche, Wade Thompson
{"title":"Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark.","authors":"Anton Pottegård, Lars Ulrik Gerdes, Jakob Langballe Wetche, Wade Thompson","doi":"10.1093/ehjcvp/pvae043","DOIUrl":"10.1093/ehjcvp/pvae043","url":null,"abstract":"<p><strong>Aims: </strong>Examine whether the low-density lipoprotein cholesterol (LDL -C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease.</p><p><strong>Methods and results: </strong>We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the region directly measure LDL -C whereas four laboratories calculate LDL -C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL -C determined during 2018-2019. There were 202 807 people who had LDL -C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL -C measurement. The median reported LDL -C was 3.40 mmol/L [interquartile range (IQR) 2.90-4.00] for those with a direct measurement vs. 3.00 mmol/L (IQR 2.40-3.50) for those with calculated LDL -C. For those with direct measurement, re-calculated LDL -C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL -C measurement. Among those with directly measured LDL -C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL -C. Direct LDL -C measurement led to higher odds of having a statin initiated compared with calculated LDL -C (adjusted odds ratio 1.23, 95% CI 1.17-1.30); for those with triglycerides >1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30-1.52).</p><p><strong>Conclusion: </strong>Differences in the reporting of LDL -C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"500-504"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"2024 ESC Guidelines on Chronic Coronary Syndromes: What is New in Pharmacotherapy?","authors":"Mattia Galli,Felice Gragnano,Christiaan Vrints,Felicita Andreotti","doi":"10.1093/ehjcvp/pvae069","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae069","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":"191 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GPVI inhibition: Advancing antithrombotic therapy in cardiovascular disease.","authors":"Alexandre Slater, Sophia Khattak, Mark R Thomas","doi":"10.1093/ehjcvp/pvae018","DOIUrl":"10.1093/ehjcvp/pvae018","url":null,"abstract":"<p><p>Glycoprotein (GP) VI (GPVI) plays a major role in thrombosis but not haemostasis, making it a promising antithrombotic target. The primary role of GPVI on the surface of platelets is a signalling receptor for collagen, which is one of the most potent thrombotic sub-endothelial components that is exposed by atherosclerotic plaque rupture. Inhibition of GPVI has therefore been investigated as a strategy for treatment and prevention of atherothrombosis, such as during stroke and acute coronary syndromes. A range of specific GPVI inhibitors have been characterized, and two of these inhibitors, glenzocimab and revacept, have completed Phase II clinical trials in ischaemic stroke. In this review, we summarize mechanisms of GPVI activation and the latest progress of clinically tested GPVI inhibitors, including their mechanisms of action. By focusing on what is known about GPVI activation, we also discuss whether alternate strategies could be used to target GPVI.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"465-473"},"PeriodicalIF":5.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Re: Shahim et al., 2024 \"Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction\".","authors":"Arina A Tamborska, Charles F Bray, Tobias Kurth","doi":"10.1093/ehjcvp/pvae041","DOIUrl":"10.1093/ehjcvp/pvae041","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"476-477"},"PeriodicalIF":5.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aspirin-free strategy for percutaneous coronary intervention in acute coronary syndrome based on the subtypes of acute coronary syndrome and high bleeding risk: the STOPDAPT-3 trial.","authors":"Yuki Obayashi, Masahiro Natsuaki, Hirotoshi Watanabe, Takeshi Morimoto, Ko Yamamoto, Ryusuke Nishikawa, Kenji Ando, Satoru Suwa, Tsuyoshi Isawa, Hiroyuki Takenaka, Tetsuya Ishikawa, Hideo Tokuyama, Hiroki Sakamoto, Takanari Fujita, Mamoru Nanasato, Hideki Okayama, Tenjin Nishikura, Hidekuni Kirigaya, Koji Nishida, Koh Ono, Takeshi Kimura","doi":"10.1093/ehjcvp/pvae009","DOIUrl":"10.1093/ehjcvp/pvae009","url":null,"abstract":"<p><strong>Background and aims: </strong>High bleeding risk (HBR) and acute coronary syndrome (ACS) subtypes are critical in determining bleeding and cardiovascular event risk after percutaneous coronary intervention (PCI).</p><p><strong>Methods and results: </strong>In 4476 ACS patients enrolled in the STOPDAPT-3, where the no-aspirin and dual antiplatelet therapy (DAPT) strategies after PCI were randomly compared, the pre-specified subgroup analyses were conducted based on HBR/non-HBR and ST-segment elevation myocardial infarction (STEMI)/non-ST-segment elevation ACS (NSTE-ACS). The co-primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5, and the co-primary cardiovascular endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke at 1 month. Irrespective of the subgroups, the effect of no-aspirin compared with DAPT was not significant for the bleeding endpoint (HBR [N = 1803]: 7.27 and 7.91%, hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.65-1.28; non-HBR [N = 2673]: 3.40 and 3.65%, HR 0.93, 95% CI 0.62-1.39; Pinteraction = 0.94; STEMI [N = 2553]: 6.58 and 6.56%, HR 1.00, 95% CI 0.74-1.35; NSTE-ACS [N = 1923]: 2.94 and 3.64%, HR 0.80, 95% CI 0.49-1.32; Pinteraction = 0.45), and for the cardiovascular endpoint (HBR: 7.87 and 5.75%, HR 1.39, 95% CI 0.97-1.99; non-HBR: 2.56 and 2.67%, HR 0.96, 95% CI 0.60-1.53; Pinteraction = 0.22; STEMI: 6.07 and 5.46%, HR 1.11, 95% CI 0.81-1.54; NSTE-ACS: 3.03 and 1.71%, HR 1.78, 95% CI 0.97-3.27; Pinteraction = 0.18).</p><p><strong>Conclusion: </strong>In patients with ACS undergoing PCI, the no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of HBR and ACS subtypes. The numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events was observed in patients with HBR and in patients with NSTE-ACS.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"374-390"},"PeriodicalIF":5.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Bruno, Florian A Wenzl, Ovidio De Filippo, Simon Kraler, Federico Giacobbe, Marco Roffi, Olivier Muller, Lorenz Räber, Christian Templin, Gaetano Maria De Ferrari, Fabrizio D'Ascenzo, Thomas F Lüscher
{"title":"Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study.","authors":"Francesco Bruno, Florian A Wenzl, Ovidio De Filippo, Simon Kraler, Federico Giacobbe, Marco Roffi, Olivier Muller, Lorenz Räber, Christian Templin, Gaetano Maria De Ferrari, Fabrizio D'Ascenzo, Thomas F Lüscher","doi":"10.1093/ehjcvp/pvae024","DOIUrl":"10.1093/ehjcvp/pvae024","url":null,"abstract":"<p><strong>Aims: </strong>Data on glycoprotein IIb/IIIa inhibitor (GPI) use in real-world acute coronary syndrome (ACS) patients following the introduction of potent P2Y12 inhibitors and newer-generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multicentre cohort of contemporary ACS patients.</p><p><strong>Methods and results: </strong>SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 year. Secondary endpoints were defined as any bleeding events, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs. 35%, P < 0.001) and thrombus (60% vs. 35%, P < 0.001) at angiography. Among the propensity score-matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE [PSM adjusted hazard ratio (HR) 0.70, 95% CI 0.49-0.99], but a higher risk of any (PSM adjusted HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adjusted HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adjusted HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups.</p><p><strong>Conclusions: </strong>In patients with ACS undergoing percutaneous coronary intervention and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"391-402"},"PeriodicalIF":5.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}