{"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":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":"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}
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.
{"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":null,"pages":null},"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}
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
Aims: 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.
Methods and results: 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.
Conclusions: 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.
{"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":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":"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}
Paul M Haller, Niema Kazem, Stefan Agewall, Claudio Borghi, Claudio Ceconi, Dobromir Dobrev, Elisabetta Cerbai, Erik Lerkevang Grove, Juan Carlos Kaski, Basil S Lewis, Alexander Niessner, Bianca Rocca, Giuseppe Rosano, Gianluigi Savarese, Renate B Schnabel, Anne Grete Semb, Samuel Sossalla, Sven Wassmann, Patrick Sulzgruber
Aims: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety.
Methods: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses.
Results: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots.
Conclusion: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.
{"title":"Oral anticoagulation in patients with left ventricular thrombus: a systematic review and meta-analysis.","authors":"Paul M Haller, Niema Kazem, Stefan Agewall, Claudio Borghi, Claudio Ceconi, Dobromir Dobrev, Elisabetta Cerbai, Erik Lerkevang Grove, Juan Carlos Kaski, Basil S Lewis, Alexander Niessner, Bianca Rocca, Giuseppe Rosano, Gianluigi Savarese, Renate B Schnabel, Anne Grete Semb, Samuel Sossalla, Sven Wassmann, Patrick Sulzgruber","doi":"10.1093/ehjcvp/pvae042","DOIUrl":"10.1093/ehjcvp/pvae042","url":null,"abstract":"<p><strong>Aims: </strong>Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety.</p><p><strong>Methods: </strong>We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses.</p><p><strong>Results: </strong>We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots.</p><p><strong>Conclusion: </strong>In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT.</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":"141283340","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":"The search for the holy grail: the balance between the risk of thrombosis and bleeding in patients.","authors":"Stefan Agewall","doi":"10.1093/ehjcvp/pvae052","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae052","url":null,"abstract":"","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":"141975406","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":"Reply to 'Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction'.","authors":"Bahira Shahim, Hong Xu, Maria Eriksdotter","doi":"10.1093/ehjcvp/pvae023","DOIUrl":"10.1093/ehjcvp/pvae023","url":null,"abstract":"","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":"140329748","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":"After 30 years, the first endothelin-receptor antagonist (Aprocitentan) is approved for the treatment of arterial hypertension.","authors":"Juan Tamargo","doi":"10.1093/ehjcvp/pvae035","DOIUrl":"10.1093/ehjcvp/pvae035","url":null,"abstract":"","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":"140956799","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}
Arvid Engström, Jonas Söderling, Anders Hviid, Björn Eliasson, Soffia Gudbjörnsdottir, Viktor Wintzell, Kristian Hveem, Christian Jonasson, Mads Melbye, Björn Pasternak, Peter Ueda
Aims: To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice.
Methods and results: Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death, and diabetic ketoacidosis. Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events [adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, (95% confidence interval 0.97-1.08)], heart failure [6.5 vs. 6.3 events per 1000 person-years; HR 1.05 (0.97-1.14)] and serious renal events [3.7 vs. 4.1 events per 1000 person-years; HR 0.97 (0.87-1.07)]. In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis.
Conclusion: Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis.
目的:在常规临床实践中,评估恩格列净与达帕格列净对2型糖尿病患者心血管和肾脏有效性和安全性的比较:队列研究使用瑞典、丹麦和挪威2014年6月至2021年6月期间全国范围内的登记数据,包括141065名安帕格列净新用户和58306名达帕格列净新用户。主要结果为重大心血管事件(心肌梗死、中风和心血管死亡)、心力衰竭(因心力衰竭住院或死亡)和严重肾脏事件(肾脏替代治疗、因肾脏事件住院和因肾脏原因死亡)。次要结果为主要结果的各个组成部分、任何原因导致的死亡和糖尿病酮症酸中毒:结果:使用empagliflozin与使用dapagliflozin发生重大心血管事件的风险相似(调整后发病率分别为15.9%和15.8%):15.9 vs. 15.8次/1000人-年;HR 1.02 [95% CI 0.97-1.08])、心力衰竭(6.5 vs. 6.3次/1000人-年;HR 1.05 [0.97-1.14])和严重肾脏事件(3.7 vs. 4.1次/1000人-年;HR 0.97 [0.87-1.07])的风险相似。在次要结局分析中,使用empagliflozin与dapagliflozin相比,心肌梗死的HR为1.00(0.93-1.07),中风为1.03(0.95-1.12),心血管死亡为1.01(0.92-1.13),任何原因死亡为1.06(1.00-1.11)、肾脏替代治疗0.77(0.60-0.99)、肾脏死亡1.20(0.75-1.93)、肾脏事件住院1.01(0.90-1.12)、糖尿病酮症酸中毒1.12(0.94-1.33):使用empagliflozin和dapagliflozin与心血管和肾脏结局、死亡率和糖尿病酮症酸中毒的风险相似。
{"title":"Comparative cardiovascular and renal effectiveness of empagliflozin and dapagliflozin: Scandinavian cohort study.","authors":"Arvid Engström, Jonas Söderling, Anders Hviid, Björn Eliasson, Soffia Gudbjörnsdottir, Viktor Wintzell, Kristian Hveem, Christian Jonasson, Mads Melbye, Björn Pasternak, Peter Ueda","doi":"10.1093/ehjcvp/pvae045","DOIUrl":"10.1093/ehjcvp/pvae045","url":null,"abstract":"<p><strong>Aims: </strong>To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice.</p><p><strong>Methods and results: </strong>Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death, and diabetic ketoacidosis. Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events [adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, (95% confidence interval 0.97-1.08)], heart failure [6.5 vs. 6.3 events per 1000 person-years; HR 1.05 (0.97-1.14)] and serious renal events [3.7 vs. 4.1 events per 1000 person-years; HR 0.97 (0.87-1.07)]. In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis.</p><p><strong>Conclusion: </strong>Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450195","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}
Aims: Proton pump inhibitors (PPIs) impair cardiac repolarization, prolong the QT interval, and may potentially be pro-arrhythmic. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We studied whether past or current PPI use is associated with OHCA in the general population.
Methods and results: We conducted a nationwide nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA-controls from the general population. Exposure to PPI was categorized into three mutually exclusive groups of current-, past-, and non-use. Conditional logistic regression analyses with adjustments for risk factors of OHCA were used to calculate the odds ratio (OR) of OHCA comparing PPI use with non-users. We identified 46 578 OHCA cases and 232 890 matched non-OHCA controls (mean: 71 years, 68.8% men). PPI was used by 8769 OHCA-cases and 21 898 non-OHCA controls, and current use of PPI was associated with increased odds of OHCA compared with non-users [OR: 1.32 (95% CI: 1.28-1.37)], while past use conferred no increase in the odds of OHCA [OR: 1.01 (95% CI: 0.98-1.04)]. This increased odds of OHCA occurred in both sexes. Finally, the ORs remained elevated when we repeated the analyses in individuals without registered ischaemic heart disease [OR: 1.36 (95% CI: 1.31-1.41)], without heart failure [OR: 1.33 (95% CI: 1.29-1.38)], or without any cardiovascular comorbidities [OR: 1.84 (95% CI: 1.70-2.00)]. Also, the OR remained elevated when H2-antagonists served as the reference group [OR: 1.28 (95% CI: 1.11-1.47)].
Conclusion: PPI use is associated with an increased risk of OHCA in the general population. Considering the widespread use of PPIs, this study raises concerns and the need for awareness to balance the benefit and risk of treatment.
目的:质子泵抑制剂(PPIs)会损害心脏复极化,延长 QT 间期,并可能导致心律失常。然而,院外心脏骤停(OHCA)的风险却鲜有研究。我们研究了在普通人群中,过去或现在使用 PPI 是否与 OHCA 相关:我们在全国范围内开展了一项巢式病例对照研究,研究对象为推测为心脏原因导致的 OHCA 病例以及与年龄/性别/OHCA 日期相匹配的非 OHCA 病例。PPI暴露分为三个相互排斥的组别,即当前使用、过去使用和未使用。在对 OHCA 风险因素进行调整后,采用条件逻辑回归分析计算使用 PPI 与未使用 PPI 的 OHCA 机率比 (OR)。我们发现了 46578 例 OHCA 病例和 232890 例匹配的非 OHCA 对照者(平均 71 岁,68.8% 为男性)。有 8769 例 OHCA 患者和 21898 例非 OHCA 对照者使用了 PPI,与未使用 PPI 的患者相比,当前使用 PPI 与 OHCA 发生几率增加有关(OR:1.32 [95%-CI:1.28-1.37]),而过去使用 PPI 不会增加 OHCA 发生几率(OR:1.01 [95%-CI:0.98-1.04])。OHCA几率的增加在男女两性中均有发生。最后,当我们对无登记缺血性心脏病(OR:1.36 [95%-CI:1.31-1.41])、无心力衰竭(OR:1.33 [95%-CI:1.29-1.38])或无任何心血管合并症(OR:1.84 [95%-CI:1.70-2.00])的个体重复进行分析时,OR 值仍然升高。此外,以 H2-拮抗剂作为参照组时,OR 值仍然升高(OR:1.28 [95%-CI:1.11-1.47]):结论:在普通人群中,使用 PPI 与 OHCA 风险增加有关。考虑到 PPIs 的广泛使用,本研究引起了人们的关注,需要提高人们的认识,以平衡治疗的益处和风险。
{"title":"Use of proton pump inhibitors is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nested case-control study.","authors":"Talip E Eroglu, Ruben Coronel, Gunnar H Gislason","doi":"10.1093/ehjcvp/pvae020","DOIUrl":"10.1093/ehjcvp/pvae020","url":null,"abstract":"<p><strong>Aims: </strong>Proton pump inhibitors (PPIs) impair cardiac repolarization, prolong the QT interval, and may potentially be pro-arrhythmic. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We studied whether past or current PPI use is associated with OHCA in the general population.</p><p><strong>Methods and results: </strong>We conducted a nationwide nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA-controls from the general population. Exposure to PPI was categorized into three mutually exclusive groups of current-, past-, and non-use. Conditional logistic regression analyses with adjustments for risk factors of OHCA were used to calculate the odds ratio (OR) of OHCA comparing PPI use with non-users. We identified 46 578 OHCA cases and 232 890 matched non-OHCA controls (mean: 71 years, 68.8% men). PPI was used by 8769 OHCA-cases and 21 898 non-OHCA controls, and current use of PPI was associated with increased odds of OHCA compared with non-users [OR: 1.32 (95% CI: 1.28-1.37)], while past use conferred no increase in the odds of OHCA [OR: 1.01 (95% CI: 0.98-1.04)]. This increased odds of OHCA occurred in both sexes. Finally, the ORs remained elevated when we repeated the analyses in individuals without registered ischaemic heart disease [OR: 1.36 (95% CI: 1.31-1.41)], without heart failure [OR: 1.33 (95% CI: 1.29-1.38)], or without any cardiovascular comorbidities [OR: 1.84 (95% CI: 1.70-2.00)]. Also, the OR remained elevated when H2-antagonists served as the reference group [OR: 1.28 (95% CI: 1.11-1.47)].</p><p><strong>Conclusion: </strong>PPI use is associated with an increased risk of OHCA in the general population. Considering the widespread use of PPIs, this study raises concerns and the need for awareness to balance the benefit and risk of treatment.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131103","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}
Background: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk.
Methods and results: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07).
Conclusions: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy.
背景:ONCO DVT研究显示,在血栓形成风险方面,对癌症相关孤立远端深静脉血栓形成(DVT)患者进行为期12个月的依多沙班治疗优于为期3个月的依多沙班治疗:在ONCO深静脉血栓研究的这一预先指定的亚组分析中,我们将患者分为服用标准埃多沙班剂量(60毫克/天;N=151)的患者和服用减量埃多沙班剂量(30毫克/天;N=450)的患者,并评估了12个月和3个月治疗的临床结果:60毫克组12个月的症状性复发性静脉血栓栓塞症累积发生率低于3个月组(1.3% vs. 11.6%,P=0.02;几率比[OR],0.12;95% CI,0.01-0.97)和30 mg(1.1% vs. 7.6%,P=0.002;OR,0.14;95% CI,0.03-0.60)埃多沙班亚组,这在不同埃多沙班剂量之间是一致的,没有显著的交互作用(P =0.90)。在 60 毫克埃多沙班亚组中,12 个月组的大出血累积发生率高于 3 个月组(14.3% 对 4.4%,P=0.046;OR,3.61;95% CI,0.97-13.52)。52),而在30毫克埃多沙班亚组中,两组之间没有显著差异(8.7% vs. 8.6%,P=0.89;OR,0.97;95% CI,0.49-1.91),表明存在潜在的相互作用(P=0.07):就血栓风险而言,12个月的依多沙班方案治疗癌症相关孤立远端深静脉血栓一直优于3个月的方案。然而,由于长期抗凝治疗可能会增加出血风险,因此建议谨慎使用标准剂量的依多沙班。
{"title":"Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.","authors":"Ryuki Chatani, Yugo Yamashita, Takeshi Morimoto, Nao Muraoka, Michihisa Umetsu, Yuji Nishimoto, Takuma Takada, Yoshito Ogihara, Tatsuya Nishikawa, Nobutaka Ikeda, Kazunori Otsui, Daisuke Sueta, Yukari Tsubata, Masaaki Shoji, Ayumi Shikama, Yutaka Hosoi, Yasuhiro Tanabe, Kengo Tsukahara, Naohiko Nakanishi, Kitae Kim, Satoshi Ikeda, Kazunori Mushiake, Kazushige Kadota, Koh Ono, Takeshi Kimura","doi":"10.1093/ehjcvp/pvae028","DOIUrl":"10.1093/ehjcvp/pvae028","url":null,"abstract":"<p><strong>Background: </strong>The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk.</p><p><strong>Methods and results: </strong>In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07).</p><p><strong>Conclusions: </strong>A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy.</p><p><strong>Trial registration number: </strong>NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854858","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}