{"title":"Focus on different lipid-lowering treatment and genetic testing for optimal pharmacotherapy use in the clinic.","authors":"Stefan Agewall","doi":"10.1093/ehjcvp/pvae061","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae061","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371349","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}
Background: 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.
Methods and results: 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.
Conclusions: 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.
背景:众所周知,降压药可降低心血管疾病死亡率,但不同类型的降压药在寿命中的作用尚未明确。此外,其潜在机制仍不清楚:为了最大限度地减少混杂因素,我们采用孟德尔随机法评估了不同类型的降压药对长寿的作用,并通过蛋白质研究了其作用途径。与药物靶基因相对应的收缩压(SBP)相关基因变异被用作遗传工具。与寿命相关的遗传变异来自一项大型全基因组关联研究,其中包括来自英国生物库和 LifeGen 的 100 万欧洲参与者。对于重要的抗高血压药物类别,我们进行了性别特异性分析、药物靶标分析和共定位分析。为了研究中介途径,我们评估了2291种血浆蛋白与寿命的关联,并研究了药物类别与影响寿命的蛋白的关联:经多重检验校正后,基因替代的β受体阻滞剂(BBs)、钙通道阻滞剂(CCBs)和血管扩张剂与延长寿命有关(BBs:SBP每降低5 mmHg,BBs的寿命为2.03,95% CI为0.78-3.28;CCBs:SBP每降低5 mmHg,CCBs的寿命为3.40,95% CI为1.28):3.40,95% CI 1.47 至 5.33,血管扩张剂:2.92,95% CI 1.08 至 4.77)。BB类和CCB类药物对男性的益处更为明显。ADRB1、CACNA2D2、CACNB3、CPT1A、CPT2和EDNRA基因与延长寿命有关,其中CPT2得到了共定位证据的进一步支持。86种蛋白质与寿命有关,其中4种蛋白质受CCB影响。CDH1可能介导了CCBs与寿命之间的关联:结论:BBs、CCBs和血管扩张剂可延长寿命,其中BBs和CCBs可能存在性别差异。CCBs对寿命的作用部分由CDH1介导。对潜在的蛋白质靶点进行优先排序可为健康老龄化提供新的见解。
{"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":null,"pages":null},"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}
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
Aims: 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).
Methods and results: 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.
Conclusion: 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.
{"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":null,"pages":null},"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}
Anton Pottegård, Lars Ulrik Gerdes, Jakob Langballe Wetche, Wade Thompson
Aims: Examine whether the low-density lipoprotein cholesterol (LDL -C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease.
Methods and results: 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).
Conclusion: Differences in the reporting of LDL -C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.
{"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":null,"pages":null},"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":null,"pages":null},"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}
Yan Xu,Caroline Mallity,Erin Collins,Deborah M Siegal,Tzu-Fei Wang,Marc Carrier
AIMSIncidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site.METHODS AND RESULTSWe conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites.CONCLUSIONBased on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.
摘要门诊癌症患者的动脉血栓栓塞症(ATE)发病率因原发肿瘤部位而异。然而,目前还不清楚这是否会改变预防性抗凝治疗对预防 ATE 的利弊分析。因此,我们根据原发肿瘤部位系统地评估了非卧床癌症患者使用抗凝剂预防 ATE 的有效性和安全性。方法和结果我们使用 Medline、Embase、SCOPUS 和 CENTRAL 进行了系统性回顾,纳入了在开始接受肿瘤指导的全身治疗的非卧床癌症患者中比较预防性抗凝与无抗凝的随机试验。我们使用随机效应模型按原发肿瘤部位对无症状 ATE(急性缺血性中风、急性心肌梗死或外周动脉闭塞)和大出血的发生率以及抗凝引起的风险差异 (RD) 进行了元分析。我们纳入了 10 项随机对照试验,共有 9875 名患者参加,随访时间从 3.3 个月到 68 个月(中位数为 6.6 个月)不等。虽然预防性抗凝治疗并未降低总体ATE风险(RD -0.49%;95% CI -0.49%至0.01%;I2=0%),但它对胰腺癌患者具有保护作用(RD -3.2%;95%CI -5.7%至-0.8%;I2=0%),且未发现大出血增加(RD -1.4%;95% CI -4.6%至1.8%;I2=0%)。结论根据现有证据,预防性抗凝并不能降低门诊癌症患者的 ATE 风险。但是,我们观察到随机接受抗凝治疗的胰腺癌患者的 ATE 发生率较低。在未来的研究中,应该对预防性抗凝剂的使用以减少胰腺癌患者的 ATE 进行评估。
{"title":"Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Yan Xu,Caroline Mallity,Erin Collins,Deborah M Siegal,Tzu-Fei Wang,Marc Carrier","doi":"10.1093/ehjcvp/pvae068","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae068","url":null,"abstract":"AIMSIncidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site.METHODS AND RESULTSWe conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites.CONCLUSIONBased on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248669","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}
Katarina Mars, Sophia Humphries, Philip Leissner, Martin Jonsson, Patric Karlström, Jörg Lauermann, Joakim Alfredsson, Thomas Kellerth, Annica Ravn-Fischer, David Erlinge, Bertil Lindahl, Troels Yndigegn, Tomas Jernberg, Claes Held, Erik M G Olsson, Robin Hofmann
Aims: In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being.
Methods and results: From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P > 0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results.
Conclusion: Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.
{"title":"Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function-a prespecified substudy from REDUCE-AMI.","authors":"Katarina Mars, Sophia Humphries, Philip Leissner, Martin Jonsson, Patric Karlström, Jörg Lauermann, Joakim Alfredsson, Thomas Kellerth, Annica Ravn-Fischer, David Erlinge, Bertil Lindahl, Troels Yndigegn, Tomas Jernberg, Claes Held, Erik M G Olsson, Robin Hofmann","doi":"10.1093/ehjcvp/pvae062","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae062","url":null,"abstract":"<p><strong>Aims: </strong>In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being.</p><p><strong>Methods and results: </strong>From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P > 0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results.</p><p><strong>Conclusion: </strong>Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105745","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}
Philip Enström, Andreas Martinsson, Mary Rezk, Susanne Nielsen, Erik Björklund, Maya Landenhed-Smith, Emily Pan, Anders Jeppsson
Aims: Early identification of patients with increased bleeding risk increases the possibility to individualize antithrombotic treatment. We validated the PRECISE-DAPT score, originally developed to estimate bleeding risk in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), in coronary artery bypass grafting (CABG) patients.
Methods and results: All patients who underwent first time, isolated CABG in Sweden 2009-2020 and survived until discharge were included. The four-item PRECISE-DAPT score, based on age, estimated glomerular filtration rate, preoperative haemoglobin concentration, and previous spontaneous bleeding, was calculated in patients discharged on DAPT (n = 6 838), or antiplatelet monotherapy (n = 15 406). High bleeding risk was defined as a score ≥ 25 in accordance with previous studies and major bleeding as hospitalization due to bleeding. Associations were assessed by C-statistics and Cox regression models.Major bleeding occurred during the first postoperative year in 130 patients (1.9%) in the DAPT group, and in 197 patients (1.3%) in the monotherapy group. The score identified 32.9% of the patients in the DAPT group and 38.2% in monotherapy groups as having high bleeding risk. The area under the ROC-curve for the score was 0.67 (95%CI 0.62-0.72) for DAPT and 0.71 (0.67-0.74) for monotherapy. The hazard ratio for high bleeding risk vs. very low risk was 4.14 (2.07-8.26) for DAPT patients, and 4.95 (2.61-9.39) for monotherapy patients, both p < 0.001.
Conclusions: The PRECISE-DAPT identifies patients with increased risk for major bleeding after discharge following CABG with moderate accuracy. The accuracy is comparable to what previously has been reported for patients after PCI.
{"title":"The four-item PRECISE-DAPT score identifies coronary artery bypass grafting patients with increased risk for post-discharge major bleeding.","authors":"Philip Enström, Andreas Martinsson, Mary Rezk, Susanne Nielsen, Erik Björklund, Maya Landenhed-Smith, Emily Pan, Anders Jeppsson","doi":"10.1093/ehjcvp/pvae060","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae060","url":null,"abstract":"<p><strong>Aims: </strong>Early identification of patients with increased bleeding risk increases the possibility to individualize antithrombotic treatment. We validated the PRECISE-DAPT score, originally developed to estimate bleeding risk in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), in coronary artery bypass grafting (CABG) patients.</p><p><strong>Methods and results: </strong>All patients who underwent first time, isolated CABG in Sweden 2009-2020 and survived until discharge were included. The four-item PRECISE-DAPT score, based on age, estimated glomerular filtration rate, preoperative haemoglobin concentration, and previous spontaneous bleeding, was calculated in patients discharged on DAPT (n = 6 838), or antiplatelet monotherapy (n = 15 406). High bleeding risk was defined as a score ≥ 25 in accordance with previous studies and major bleeding as hospitalization due to bleeding. Associations were assessed by C-statistics and Cox regression models.Major bleeding occurred during the first postoperative year in 130 patients (1.9%) in the DAPT group, and in 197 patients (1.3%) in the monotherapy group. The score identified 32.9% of the patients in the DAPT group and 38.2% in monotherapy groups as having high bleeding risk. The area under the ROC-curve for the score was 0.67 (95%CI 0.62-0.72) for DAPT and 0.71 (0.67-0.74) for monotherapy. The hazard ratio for high bleeding risk vs. very low risk was 4.14 (2.07-8.26) for DAPT patients, and 4.95 (2.61-9.39) for monotherapy patients, both p < 0.001.</p><p><strong>Conclusions: </strong>The PRECISE-DAPT identifies patients with increased risk for major bleeding after discharge following CABG with moderate accuracy. The accuracy is comparable to what previously has been reported for patients after PCI.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008490","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}
Background and aims: High bleeding risk (HBR) and acute coronary syndrome (ACS) subtypes are critical in determining bleeding and cardiovascular event risk after percutaneous coronary intervention (PCI).
Methods and results: 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).
Conclusion: 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.
{"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":null,"pages":null},"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}