Casper Binding, Paul Blanche, Gregory Y H Lip, Anne-Lise Kamper, Christina J Y Lee, Laila Staerk, Gunnar Gislason, Christian Torp-Pedersen, Jonas Bjerring Olesen, Anders Nissen Bonde
Background and aims: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function.
Methods: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding.
Results: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2.
Conclusions: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.
{"title":"Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.","authors":"Casper Binding, Paul Blanche, Gregory Y H Lip, Anne-Lise Kamper, Christina J Y Lee, Laila Staerk, Gunnar Gislason, Christian Torp-Pedersen, Jonas Bjerring Olesen, Anders Nissen Bonde","doi":"10.1093/ehjcvp/pvae016","DOIUrl":"10.1093/ehjcvp/pvae016","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function.</p><p><strong>Methods: </strong>Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding.</p><p><strong>Results: </strong>Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2.</p><p><strong>Conclusions: </strong>Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944038","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}
Morten Würtz, Kevin Kris Warnakula Olesen, Deepak L Bhatt, Salim Yusuf, Eva Muehlhofer, John W Eikelboom, Michael Maeng
Aims: Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial.
Methods and results: COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients.
Conclusion: As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.
目的:指南建议对缺血风险较高的慢性冠状动脉综合征(CCS)患者使用阿司匹林和利伐沙班延长双通道抑制(DPI)。CHADS-P2A2RC评分可提高风险预测能力,为这些患者分配抗血栓治疗提供依据。本研究根据COMPASS试验中CCS患者的CHADS-P2A2RC评分所划分的基线风险,评估了DPI治疗的净临床获益:COMPASS试验中的CCS患者(n = 14 670)随机接受阿司匹林单独治疗或DPI治疗,根据CHADS-P2A2RC评分进行心血管风险分层。终点为主要心血管不良事件(MACE)、全因死亡、致命/危重器官出血和复合不良事件(MACE和出血)。净临床获益为30个月内MACE和出血的风险差异:结果:高危人群(CHADS-P2A2RC ≥ 4)的30个月MACE(7.9% vs 3.9%,HR 2.01,95% CI 1.83-2.18)和致命/危重器官出血(1.2% vs 0.8%,HR 1.49 [1.06-1.92])发生率高于低危/中危人群(CHADS-P2A2RC 结论:根据CHADS-P2A2RC分类,高危人群(CHADS-P2A2RC ≥ 4)的30个月MACE发生率高于低危/中危人群(CHADS-P2A2RC ≥ 4):根据 CHADS-P2A2RC 评分进行分类,低危/中危和高危 CCS 患者从 DPI 治疗中获得的净临床获益和全因死亡减少率相似。
{"title":"Net clinical benefit of extended dual pathway inhibition according to baseline risk in patients with chronic coronary syndrome: a COMPASS substudy.","authors":"Morten Würtz, Kevin Kris Warnakula Olesen, Deepak L Bhatt, Salim Yusuf, Eva Muehlhofer, John W Eikelboom, Michael Maeng","doi":"10.1093/ehjcvp/pvae017","DOIUrl":"10.1093/ehjcvp/pvae017","url":null,"abstract":"<p><strong>Aims: </strong>Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial.</p><p><strong>Methods and results: </strong>COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients.</p><p><strong>Conclusion: </strong>As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058988","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}
Giovanni Occhipinti, Claudio Laudani, Marco Spagnolo, Simone Finocchiaro, Placido Maria Mazzone, Denise Cristiana Faro, Maria Sara Mauro, Carla Rochira, Federica Agnello, Daniele Giacoppo, Nicola Ammirabile, Davide Landolina, Antonino Imbesi, Giuseppe Sangiorgio, Antonio Greco, Davide Capodanno
The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.
{"title":"Pharmacological and clinical appraisal of factor XI inhibitor drugs.","authors":"Giovanni Occhipinti, Claudio Laudani, Marco Spagnolo, Simone Finocchiaro, Placido Maria Mazzone, Denise Cristiana Faro, Maria Sara Mauro, Carla Rochira, Federica Agnello, Daniele Giacoppo, Nicola Ammirabile, Davide Landolina, Antonino Imbesi, Giuseppe Sangiorgio, Antonio Greco, Davide Capodanno","doi":"10.1093/ehjcvp/pvae002","DOIUrl":"10.1093/ehjcvp/pvae002","url":null,"abstract":"<p><p>The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402465","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}
K Enge, A Tveit, S Enger, S Onarheim, A H Pripp, P S Rønningen, M G Solberg, R Byrkjeland, K Andresen, A Halsen, H A Aulie, T Steinsvik, C Hall, S R Ulimoen
Aims: Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the longer-term effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation after six months.
Methods and results: Men and women with permanent atrial fibrillation and preserved left ventricular systolic function were randomised to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a six-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ±7 years, 28 women) were randomised. After six months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6 - 589.1, P<0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity.
Conclusion: Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent atrial fibrillation.
{"title":"Diltiazem reduces levels of NT-proBNP and improves symptoms compared with metoprolol in patients with permanent atrial fibrillation.","authors":"K Enge, A Tveit, S Enger, S Onarheim, A H Pripp, P S Rønningen, M G Solberg, R Byrkjeland, K Andresen, A Halsen, H A Aulie, T Steinsvik, C Hall, S R Ulimoen","doi":"10.1093/ehjcvp/pvae032","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae032","url":null,"abstract":"<p><strong>Aims: </strong>Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the longer-term effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation after six months.</p><p><strong>Methods and results: </strong>Men and women with permanent atrial fibrillation and preserved left ventricular systolic function were randomised to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a six-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ±7 years, 28 women) were randomised. After six months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6 - 589.1, P<0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity.</p><p><strong>Conclusion: </strong>Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent atrial fibrillation.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852303","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, P Gabriel Steg, Frank L J Visseren
Background and 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 CVD risk in patients with atherosclerotic cardiovascular disease (ASCVD).
Methods: Participants from REDUCE-IT with ASCVD were included (n = 5,785). 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 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.
Results: 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), 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.
Conclusions: 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, P Gabriel Steg, Frank L J Visseren","doi":"10.1093/ehjcvp/pvae030","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae030","url":null,"abstract":"<p><strong>Background and 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 CVD risk in patients with atherosclerotic cardiovascular disease (ASCVD).</p><p><strong>Methods: </strong>Participants from REDUCE-IT with ASCVD were included (n = 5,785). 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 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.</p><p><strong>Results: </strong>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), 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>Conclusions: </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":7.1,"publicationDate":"2024-04-27","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}
Mette Søgaard, Anne Gulbech Ording, Flemming Skjøth, Torben Bjerregaard Larsen, Peter Brønnum Nielsen
Aims: Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients.
Methods and results: Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%.
Conclusion: Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care.
目的:尽管虚弱的心房颤动(AF)患者具有卒中和治疗相关出血并发症的高风险,但抗凝治疗的安全性和有效性的证据仍然很少。本研究探讨了DOAC与华法林在虚弱房颤患者中的有效性和安全性。方法和结果:全国基于登记的队列研究,包括32048例抗凝naïve体弱患者(中位年龄80岁,53%女性),2012-2020年发生房颤。虚弱程度采用医院虚弱风险评分进行评估。为了解决基线混淆,我们应用治疗加权逆概率(IPTW)和边际结构模型加权合并回归来计算加权风险比(wHR)以及比较特定DOAC剂量与华法林在血栓栓塞和大出血方面的风险差异。房颤诊断后,6747例(21.1%)开始使用华法林,17076例(50.3%)开始使用标准剂量DOAC, 9179例(28.6%)开始使用减少剂量DOAC。在IPTW伪人群中的比较有效性分析显示,标准剂量DOAC和华法林之间的血栓栓塞风险相似(wHR 0.95, 95% CI 0.80-1.13),降低剂量DOAC和华法林之间的wHR 0.97, 95% CI 0.77-1.23)。与华法林相比,DOAC的1年无血栓栓塞事件生存率差异为-0.2%,无论剂量如何。与华法林相比,标准剂量DOAC (wHR 0.69, 95% CI 0.59-0.87)和降低剂量DOAC (wHR 0.67, 95% CI 0.55-0.81)的大出血风险显著降低。与DOAC的一年出血风险差异范围为-1.3%和-3.0%。结论:我们的研究结果表明,与华法林相比,在常规护理的虚弱房颤患者中,标准和降低DOAC方案的血栓栓塞风险相当,出血风险显著降低。
{"title":"Effectiveness and safety of direct oral anticoagulation vs. warfarin in frail patients with atrial fibrillation.","authors":"Mette Søgaard, Anne Gulbech Ording, Flemming Skjøth, Torben Bjerregaard Larsen, Peter Brønnum Nielsen","doi":"10.1093/ehjcvp/pvad091","DOIUrl":"10.1093/ehjcvp/pvad091","url":null,"abstract":"<p><strong>Aims: </strong>Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients.</p><p><strong>Methods and results: </strong>Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%.</p><p><strong>Conclusion: </strong>Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294969","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}
Xinyi Gao, Nan Zhang, Lei Lu, Tianyu Gao, Oscar Hou In Chou, Wing Tak Wong, Carlin Chang, Abraham Ka Chung Wai, Gregory Y H Lip, Qingpeng Zhang, Gary Tse, Tong Liu, Jiandong Zhou
Background and aims: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope.
Methods and results: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline.
Conclusion: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.
{"title":"New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study.","authors":"Xinyi Gao, Nan Zhang, Lei Lu, Tianyu Gao, Oscar Hou In Chou, Wing Tak Wong, Carlin Chang, Abraham Ka Chung Wai, Gregory Y H Lip, Qingpeng Zhang, Gary Tse, Tong Liu, Jiandong Zhou","doi":"10.1093/ehjcvp/pvad086","DOIUrl":"10.1093/ehjcvp/pvad086","url":null,"abstract":"<p><strong>Background and aims: </strong>Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope.</p><p><strong>Methods and results: </strong>This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline.</p><p><strong>Conclusion: </strong>Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590623","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}
Bahira Shahim, Hong Xu, Kristina Haugaa, Henrik Zetterberg, Juliane Jurga, Dorota Religa, Maria Eriksdotter
Background: Cholinesterase inhibitors (ChEIs) are the first-line symptomatic pharmacologic treatment for patients with mild-to-moderate Alzheimer's disease (AD). Although the target organ for this group of drugs is the brain, inhibition of the enzyme may affect cardiac function through vagotonic and anti-inflammatory effects.
Objective: To assess the impact of ChEIs on outcomes in patients with AD who have experienced myocardial infarction (MI) prior to the AD diagnosis.
Methods: Patients who had experienced MI before they were diagnosed with AD or Alzheimer's mixed dementia between 2008 and 2018 were identified from the Swedish Dementia Registry (SveDem, www.svedem.se), which was linked to the National Patient Registry to obtain data on MI and mortality. Cox proportional hazards regression model among a propensity score-matched dataset was performed to assess the association between ChEI treatment and clinical outcomes.
Results: Of 3198 patients with previous MI and a diagnosis of AD or mixed dementia, 1705 (53%) were on treatment with ChEIs. Patients treated with ChEIs were more likely to be younger and have a better overall cardiovascular (CV) risk profile. The incidence rate of all-cause death (per 1000 patient-years) in the propensity-matched cohort of 1016 ChEI users and 1016 non-users was 168.6 in patients on treatment with ChEIs compared with 190.7 in patients not on treatment with ChEIs. In this propensity-matched cohort, treatment with ChEIs was associated with a significantly lower risk of all-cause death (adjusted hazard ratio 0.81, 95% confidence interval 0.71-0.92) and a greater reduction with higher doses of ChEIs. While in the unadjusted analysis, ChEIs were associated with a lower risk of both CV and non-CV death, only the association with non-CV death remained significant after accounting for baseline differences.
Conclusion: Treatment with ChEIs was associated with a significantly reduced risk of all-cause death, driven by lower rates of non-CV death in a nationwide cohort of patients with previous MI and a diagnosis of AD or mixed dementia. These associations were greater with higher ChEI doses.
Condensed abstract: We assessed the association between cholinesterase inhibitors (ChEIs) and clinical outcomes in a nationwide cohort of patients with previous myocardial infarction (MI) and a diagnosis of Alzheimer's disease (AD) or mixed dementi. In propensity-matched analysis, treatment with ChEIs was associated with a 19% reduction in all-cause death driven by non-cardiovascular death. The reduction in all-cause death was greater with the higher doses of ChEIs.
{"title":"Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction.","authors":"Bahira Shahim, Hong Xu, Kristina Haugaa, Henrik Zetterberg, Juliane Jurga, Dorota Religa, Maria Eriksdotter","doi":"10.1093/ehjcvp/pvad102","DOIUrl":"10.1093/ehjcvp/pvad102","url":null,"abstract":"<p><strong>Background: </strong>Cholinesterase inhibitors (ChEIs) are the first-line symptomatic pharmacologic treatment for patients with mild-to-moderate Alzheimer's disease (AD). Although the target organ for this group of drugs is the brain, inhibition of the enzyme may affect cardiac function through vagotonic and anti-inflammatory effects.</p><p><strong>Objective: </strong>To assess the impact of ChEIs on outcomes in patients with AD who have experienced myocardial infarction (MI) prior to the AD diagnosis.</p><p><strong>Methods: </strong>Patients who had experienced MI before they were diagnosed with AD or Alzheimer's mixed dementia between 2008 and 2018 were identified from the Swedish Dementia Registry (SveDem, www.svedem.se), which was linked to the National Patient Registry to obtain data on MI and mortality. Cox proportional hazards regression model among a propensity score-matched dataset was performed to assess the association between ChEI treatment and clinical outcomes.</p><p><strong>Results: </strong>Of 3198 patients with previous MI and a diagnosis of AD or mixed dementia, 1705 (53%) were on treatment with ChEIs. Patients treated with ChEIs were more likely to be younger and have a better overall cardiovascular (CV) risk profile. The incidence rate of all-cause death (per 1000 patient-years) in the propensity-matched cohort of 1016 ChEI users and 1016 non-users was 168.6 in patients on treatment with ChEIs compared with 190.7 in patients not on treatment with ChEIs. In this propensity-matched cohort, treatment with ChEIs was associated with a significantly lower risk of all-cause death (adjusted hazard ratio 0.81, 95% confidence interval 0.71-0.92) and a greater reduction with higher doses of ChEIs. While in the unadjusted analysis, ChEIs were associated with a lower risk of both CV and non-CV death, only the association with non-CV death remained significant after accounting for baseline differences.</p><p><strong>Conclusion: </strong>Treatment with ChEIs was associated with a significantly reduced risk of all-cause death, driven by lower rates of non-CV death in a nationwide cohort of patients with previous MI and a diagnosis of AD or mixed dementia. These associations were greater with higher ChEI doses.</p><p><strong>Condensed abstract: </strong>We assessed the association between cholinesterase inhibitors (ChEIs) and clinical outcomes in a nationwide cohort of patients with previous myocardial infarction (MI) and a diagnosis of Alzheimer's disease (AD) or mixed dementi. In propensity-matched analysis, treatment with ChEIs was associated with a 19% reduction in all-cause death driven by non-cardiovascular death. The reduction in all-cause death was greater with the higher doses of ChEIs.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466503","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}