Raffaele Piccolo, Fiorenzo Simonetti, Marisa Avvedimento, Maria Cutillo, Mario Enrico Canonico, Valeria Conti, Giuseppe Gargiulo, Roberta Paolillo, Fabrizio Dal Piaz, Amelia Filippelli, Bruno Charlier, Alessandra Spinelli, Stefano Cristiano, Plinio Cirillo, Luigi Di Serafino, Anna Franzone, Giovanni Esposito
{"title":"Ticagrelor 60 vs. 90 mg in elderly ACS patients undergoing PCI: a randomized, crossover trial.","authors":"Raffaele Piccolo, Fiorenzo Simonetti, Marisa Avvedimento, Maria Cutillo, Mario Enrico Canonico, Valeria Conti, Giuseppe Gargiulo, Roberta Paolillo, Fabrizio Dal Piaz, Amelia Filippelli, Bruno Charlier, Alessandra Spinelli, Stefano Cristiano, Plinio Cirillo, Luigi Di Serafino, Anna Franzone, Giovanni Esposito","doi":"10.1093/ehjcvp/pvae054","DOIUrl":"10.1093/ehjcvp/pvae054","url":null,"abstract":"<p><strong>Aims: </strong>Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI).</p><p><strong>Methods and results: </strong>PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg.</p><p><strong>Conclusion: </strong>Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723336","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}
Gert Mayer, Dobromir Dobrev, Juan Carlos Kaski, Anne Grete Semb, Kurt Huber, Andreas Zirlik, Stefan Agewall, Heinz Drexel
{"title":"Management of dyslipidaemia in patients with comorbidities: facing the challenge.","authors":"Gert Mayer, Dobromir Dobrev, Juan Carlos Kaski, Anne Grete Semb, Kurt Huber, Andreas Zirlik, Stefan Agewall, Heinz Drexel","doi":"10.1093/ehjcvp/pvae058","DOIUrl":"10.1093/ehjcvp/pvae058","url":null,"abstract":"<p><p>Dyslipidaemia is a common chronic kidney disease (CKD) and contributes to excessively elevated cardiovascular mortality. The pathophysiology is complex and modified by comorbidities like the presence/absence of proteinuria, diabetes mellitus or drug treatment. This paper provides an overview of currently available treatment options. We focused on individuals with CKD and excluded those on renal replacement therapy (haemodialysis, peritoneal dialysis, or kidney transplantation). The use of statins is safe and recommended in most patients, but guidelines vary with respect to low-density lipoprotein (LDL) cholesterol goals. While no dedicated primary or secondary prevention studies are available for pro-protein convertase subtilisin/kexin type 9 inhibitors, secondary analyses of large outcome trials reveal no effect modification on endpoints by the presence of CKD. Similar data have been shown for bempedoic acid, but no definite conclusion can be drawn with respect to efficacy and safety. No outcome trials are available for inclisiran while the cholesterol lowering effects seem to be unaffected by CKD. Finally, the value of fibrates and icosapent ethyl in CKD is unclear. Lipid abnormalities contribute to the massive cardiovascular disease burden in CKD. Lowering of LDL cholesterol with statins (and most likely PCSK9 inhibitors) reduces the event rate and thus statin therapy should be initiated in almost all individuals. Other interventions (bempedoic acid, inclisiran, fibrates, or icosapent ethyl) currently need a case-by-case decision before prescription.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995594","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}
Bruna Gigante, Juan Tamargo, Stefan Agewall, Dan Atar, Jurrien Ten Berg, Gianluca Campo, Elisabetta Cerbai, Christina Christersson, Dobromir Dobrev, Péter Ferdinandy, Tobias Geisler, Diana A Gorog, Erik L Grove, Juan Carlos Kaski, Andrea Rubboli, Sven Wassmann, Håkan Wallen, Bianca Rocca
{"title":"Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis.","authors":"Bruna Gigante, Juan Tamargo, Stefan Agewall, Dan Atar, Jurrien Ten Berg, Gianluca Campo, Elisabetta Cerbai, Christina Christersson, Dobromir Dobrev, Péter Ferdinandy, Tobias Geisler, Diana A Gorog, Erik L Grove, Juan Carlos Kaski, Andrea Rubboli, Sven Wassmann, Håkan Wallen, Bianca Rocca","doi":"10.1093/ehjcvp/pvae064","DOIUrl":"10.1093/ehjcvp/pvae064","url":null,"abstract":"<p><p>Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139682","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}
Wojciech Nazar, Jan Romantowski, Marek Niedoszytko, Ludmiła Daniłowicz-Szymanowicz
{"title":"Cardiac adverse drug reactions to COVID-19 vaccines. A cross-sectional study based on the Europe-wide data.","authors":"Wojciech Nazar, Jan Romantowski, Marek Niedoszytko, Ludmiła Daniłowicz-Szymanowicz","doi":"10.1093/ehjcvp/pvae063","DOIUrl":"10.1093/ehjcvp/pvae063","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to analyse serious cardiac adverse drug reactions to COVID-19 vaccines from the Europe-wide EudraVigilance database.</p><p><strong>Methods and results: </strong>In this retrospective, cross-sectional study, the EudraVigilance database was searched to identify suspected serious cardiac post-vaccination adverse drug reactions to COVID-19 vaccines. This data was coupled with the number of total vaccine doses administered in the European Economic Area for Comirnaty (Pfizer BioNTech), Spikevax (Moderna), Vaxzevria (AstraZeneca), Jcovden (Janssen), Nuvaxovid (Novavax), products, available from the European Centre for Disease Prevention and Control 'Vaccine Tracker' database. The analysis included 772 228 309 administered doses of eligible vaccines from the 'Vaccine Tracker' database and 86 051 eligible records of cardiac adverse drug reactions from the EudraVigilance database. The frequency of most of the investigated adverse drug reactions was very rare (<1/10 000 i.e. <100/1 000 000 doses). The lowest risk of any serious cardiac adverse drug reactions was noticed for vaccination with Comirnaty (135.5 per million doses), while Spikevax, Jcovden, Vaxzevria, and Nuvaxovid were characterized by higher risk (respectively, 140.9, 194.8, 313.6, and 1065.2 per million doses). The most common complications of vaccinations included syncope, arrhythmia, tachycardia, palpitations, angina pectoris, hypertension, myocarditis, thrombosis, and pulmonary embolism.</p><p><strong>Conclusion: </strong>The risk of serious cardiac adverse drug reactions to COVID-19 vaccines is low and the benefit of active immunization against that disease seems to outweigh the potential risk of serious post-vaccination cardiac adverse drug reactions.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035553","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}
Mattia Galli, Claudio Laudani, Giovanni Occhipinti, Marco Spagnolo, Felice Gragnano, Domenico D'Amario, Eliano Pio Navarese, Roxana Mehran, Marco Valgimigli, Davide Capodanno, Dominick J Angiolillo
{"title":"P2Y12 inhibitor monotherapy after short DAPT in acute coronary syndrome: a systematic review and meta-analysis.","authors":"Mattia Galli, Claudio Laudani, Giovanni Occhipinti, Marco Spagnolo, Felice Gragnano, Domenico D'Amario, Eliano Pio Navarese, Roxana Mehran, Marco Valgimigli, Davide Capodanno, Dominick J Angiolillo","doi":"10.1093/ehjcvp/pvae057","DOIUrl":"10.1093/ehjcvp/pvae057","url":null,"abstract":"<p><strong>Background: </strong>P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischaemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes.</p><p><strong>Methods and results: </strong>Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) vs. 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analyses were run to explore whether the effect estimate of each outcome may be affected by further studies. Seven trials encompassing 27 284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.76-1.12] and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66), and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (Pint = 0.016), all-cause death (Pint = 0.042), NACE (Pint = 0.018), and myocardial infarction (Pint = 0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT.</p><p><strong>Conclusions: </strong>In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischaemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE, and mortality compared with standard DAPT, supporting its use after aspirin discontinuation.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757989","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}
Renzo Laborante, Gianluigi Savarese, Giuseppe Patti, Domenico D'Amario
{"title":"Safety and efficacy of early initiation of sodium-glucose cotransporter-2 inhibitors after an acute coronary syndrome event: a meta-analysis of randomized controlled trials.","authors":"Renzo Laborante, Gianluigi Savarese, Giuseppe Patti, Domenico D'Amario","doi":"10.1093/ehjcvp/pvae047","DOIUrl":"10.1093/ehjcvp/pvae047","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632986","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":"Reaping the rewards of a simplified dosing regimen.","authors":"Peter E Penson, Maciej Banach","doi":"10.1093/ehjcvp/pvae073","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae073","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582478","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":"Incidence and outcomes of transient new-onset atrial fibrillation complicating acute coronary syndromes: results from a systematic review and meta-analysis.","authors":"Nadia Salerno, Jessica Ielapi, Angelica Cersosimo, Isabella Leo, Jolanda Sabatino, Salvatore De Rosa, Sabato Sorrentino, Daniele Torella","doi":"10.1093/ehjcvp/pvae066","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae066","url":null,"abstract":"<p><strong>Background: </strong>The overall risk of long-term adverse events of a transient episode of new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) remains uncertain. This meta-analysis aimed to assess the prognostic impact of transient new-onset AF complicating ACS.</p><p><strong>Methods and results: </strong>Cohort studies examining the risk of adverse events in patients with transient new-onset AF compared to those in sinus rhythm after ACS were identified through a comprehensive search of MEDLINE, Scopus, Cochrane, and Google Scholar Library. Studies reporting the incidence of ischaemic stroke events, recurrent AF, or all-cause mortality at the longest follow-up were included. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) were synthesized using inverse variance-weighted random-effects meta-analysis. In the seven observational studies included, comprising 151 735 patients, 6 597 (4.3%) experienced transient new-onset AF, which was associated with an increased risk of ischaemic stroke, recurrent AF, or all-cause mortality (HR: 2.24, 95% CI: 1.75-2.85; P < 0.0001; I2 = 30.76%; seven studies). The results remained consistent across each individual endpoint, including ischaemic stroke (HR 2.38, 95% CI: 1.64-3.44; P < 0.01; I2 = 50.2%; five studies), recurrent AF (HR 4.68, 95% CI: 2.07-10.59; P = 0.0002; I2 = 50.2%; four studies), and all-cause mortality (HR 1.36, 95% CI: 1.08-1.71; P = 0.0089; I2 = 53.25%; four studies). Meta-regression analyses revealed a significant increase in these adverse events associated with ST-elevation myocardial infarction (P = 0.001), while there was a tendency for their decrease associated with oral anticoagulant prescription at discharge (P = 0.07).</p><p><strong>Conclusions: </strong>The occurrence of transient new-onset AF is associated with an elevated long-term risk of stroke, recurrent AF, and all-cause mortality in patients with ACS. Consequently, these data urge randomized clinical trials to assess the best antithrombotic regimen while potentially helping the current treatment decision-making process for these patients.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544441","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}