Matthew M Y Lee, Toru Kondo, Ross T Campbell, Mark C Petrie, Naveed Sattar, Scott D Solomon, Muthiah Vaduganathan, Pardeep S Jhund, John J V McMurray
{"title":"Effects of renin-angiotensin system blockers on outcomes from COVID-19: a systematic review and meta-analysis of randomized controlled trials.","authors":"Matthew M Y Lee, Toru Kondo, Ross T Campbell, Mark C Petrie, Naveed Sattar, Scott D Solomon, Muthiah Vaduganathan, Pardeep S Jhund, John J V McMurray","doi":"10.1093/ehjcvp/pvad067","DOIUrl":"10.1093/ehjcvp/pvad067","url":null,"abstract":"<p><strong>Background and aims: </strong>Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials.</p><p><strong>Methods: </strong>PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.</p><p><strong>Results: </strong>Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).</p><p><strong>Conclusion: </strong>ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124496","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}
M P Bonaca, E Lesén, E Giannitsis, J Hedberg, T Jernberg, D Lambrelli, M Duong, A P Maggioni, A Ariza-Solé, J Ten Berg, R F Storey
{"title":"Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.","authors":"M P Bonaca, E Lesén, E Giannitsis, J Hedberg, T Jernberg, D Lambrelli, M Duong, A P Maggioni, A Ariza-Solé, J Ten Berg, R F Storey","doi":"10.1093/ehjcvp/pvad062","DOIUrl":"10.1093/ehjcvp/pvad062","url":null,"abstract":"<p><strong>Background: </strong>Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described.</p><p><strong>Methods: </strong>Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source.</p><p><strong>Results: </strong>A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33).</p><p><strong>Conclusions: </strong>This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132058","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}
Vikash Jaiswal, Vibhor Agrawal, Song Peng Ang, Marina Saleeb, Angela Ishak, Maha Hameed, Kripa Rajak, Kriti Kalra, Akash Jaiswal
{"title":"Post-diagnostic statin use and its association with cancer recurrence and mortality in breast cancer patients: a systematic review and meta-analysis.","authors":"Vikash Jaiswal, Vibhor Agrawal, Song Peng Ang, Marina Saleeb, Angela Ishak, Maha Hameed, Kripa Rajak, Kriti Kalra, Akash Jaiswal","doi":"10.1093/ehjcvp/pvad057","DOIUrl":"10.1093/ehjcvp/pvad057","url":null,"abstract":"<p><strong>Background: </strong>Statins are widely acknowledged for their application in patients with hypercholesterolemia to reduce cardiovascular morbidity and mortality. More recently, their potential to exert pleiotropic effects, particularly in impeding the proliferation of neoplastic cells, has attracted considerable attention. Prior studies have demonstrated that statins may mitigate cancer progression and micrometastasis. However, the benefits of statins in breast cancer have been inconclusive.</p><p><strong>Objective: </strong>The aim of this meta-analysis was to evaluate the impact of statin use following a breast cancer diagnosis on breast cancer recurrence and mortality.</p><p><strong>Methods: </strong>We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 30th May 2023. Hazard ratios (HR) were pooled using a random-effect model. The primary outcome of interest was the risk of breast cancer recurrence. The secondary outcomes included breast cancer-specific mortality and all-cause mortality.</p><p><strong>Results: </strong>A total of 15 studies with 156 448 patients were included in the final analysis. The mean age of patients between statin users and non-users was 64.59 and 59.15 years, respectively. Statin use was associated with a reduction in the recurrence of breast cancer [HR 0.76, 95% confidence interval (CI): 0.67-0.87] compared with non-statin users. This trend was similar among lipophilic statin users (HR 0.73, 95% CI: 0.63-0.85) but not for hydrophilic statin users (HR 1.17, 95% CI: 0.82-1.68). Furthermore, statin users exhibited a lower risk of breast cancer mortality (HR 0.80, 95% CI: 0.66-0.96) but all-cause mortality (HR 0.82, 95% CI: 0.66-1.02) was comparable among both groups of patients. Conversely, lipophilic statins demonstrated a reduction in both all-cause mortality (HR 0.84, 95% CI: 0.75-0.93) and breast cancer mortality (HR 0.85, 95% CI: 0.74-0.99) compared to non-statin users.</p><p><strong>Conclusion: </strong>Among patients with breast cancer, statin use post-diagnosis decreases the risk of breast cancer recurrence and breast cancer mortality. Furthermore, lipophilic statins exhibit an additional advantage of reduction in all-cause mortality.PROSPERO registration: CRD42022362011.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964734","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}
Giuditta Benincasa, Rosa Suades, Teresa Padró, Lina Badimon, Claudio Napoli
{"title":"Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases.","authors":"Giuditta Benincasa, Rosa Suades, Teresa Padró, Lina Badimon, Claudio Napoli","doi":"10.1093/ehjcvp/pvad059","DOIUrl":"10.1093/ehjcvp/pvad059","url":null,"abstract":"<p><p>Although bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been applied to thousands of individuals from the Framingham Heart Study as well as health care-associated biobanks such as the UK Biobank, the Million Veteran Program, and the CARDIoGRAMplusC4D Consortium and randomized controlled trials (i.e. ODYSSEY, FOURIER, ASPREE, and PREDIMED). These studies contributed to the development of polygenic risk scores (PRS), which emerged as novel potent genetic-oriented tools, able to calculate the individual risk of ASCVD and to predict the individual response to therapies such as statins and proprotein convertase subtilisin/kexin type 9 inhibitor. ASCVD are the first cause of death around the world including coronary heart disease (CHD), peripheral artery disease, and stroke. To achieve the goal of precision medicine and personalized therapy, advanced bioinformatic platforms are set to link clinically useful indices to heterogeneous molecular data, mainly epigenomics, transcriptomics, metabolomics, and proteomics. The DIANA study found that differential methylation of ABCA1, TCF7, PDGFA, and PRKCZ significantly discriminated patients with acute coronary syndrome from healthy subjects and their expression levels positively associated with CK-MB serum concentrations. The ARIC Study revealed several plasma proteins, acting or not in lipid metabolism, with a potential role in determining the different pleiotropic effects of statins in each subject. The implementation of molecular high-throughput studies and bioinformatic techniques into traditional cardiovascular risk prediction scores is emerging as a more accurate practice to stratify patients earlier in life and to favour timely and tailored risk reduction strategies. Of note, radiogenomics aims to combine imaging features extracted for instance by coronary computed tomography angiography and molecular biomarkers to create CHD diagnostic algorithms useful to characterize atherosclerotic lesions and myocardial abnormalities. The current view is that such platforms could be of clinical value for prevention, risk stratification, and treatment of ASCVD.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971846","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":"Balancing the risks of bleeding and ischaemia in myocardial infarction patients at high bleeding risk.","authors":"J Tjerkaski, T Jernberg, K Szummer","doi":"10.1093/ehjcvp/pvad068","DOIUrl":"10.1093/ehjcvp/pvad068","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128823","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}
Andrea Raffaele Munafò, Claudio Montalto, Marco Franzino, Lorenzo Pistelli, Gianluca Di Bella, Marco Ferlini, Sergio Leonardi, Fabrizio D'Ascenzo, Felice Gragnano, Jacopo A Oreglia, Fabrizio Oliva, Luis Ortega-Paz, Paolo Calabrò, Dominick J Angiolillo, Marco Valgimigli, Antonio Micari, Francesco Costa
{"title":"External validity of the PRECISE-DAPT score in patients undergoing PCI: a systematic review and meta-analysis.","authors":"Andrea Raffaele Munafò, Claudio Montalto, Marco Franzino, Lorenzo Pistelli, Gianluca Di Bella, Marco Ferlini, Sergio Leonardi, Fabrizio D'Ascenzo, Felice Gragnano, Jacopo A Oreglia, Fabrizio Oliva, Luis Ortega-Paz, Paolo Calabrò, Dominick J Angiolillo, Marco Valgimigli, Antonio Micari, Francesco Costa","doi":"10.1093/ehjcvp/pvad063","DOIUrl":"10.1093/ehjcvp/pvad063","url":null,"abstract":"<p><strong>Aims: </strong>To summarize the totality of evidence validating the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, ascertaining its aggregate discrimination and validation power in multiple population subsets.</p><p><strong>Methods and results: </strong>We searched electronic databases from 2017 (PRECISE-DAPT proposal) up to March 2023 for studies that reported the occurrence of out-of-hospital bleedings according to the PRECISE-DAPT score in patients receiving DAPT following percutaneous coronary intervention (PCI). Pooled odds ratios (OR) with 95% confidence interval (CI) were used as summary statistics and were calculated using a random-effects model. Primary and secondary endpoints were the occurrence of any and major bleeding, respectively. A total of 21 studies and 67 283 patients were included; 24.7% of patients (N = 16 603) were at high bleeding risk (PRECISE-DAPT score ≥25), and when compared to those at low bleeding risk, they experienced a significantly higher rate of any out-of-hospital bleeding (OR: 2.71; 95% CI: 2.24-3.29; P-value <0.001) and major bleedings (OR: 3.51; 95% CI: 2.71-4.55; P-value <0.001). Pooling data on c-stat whenever available, the PRECISE-DAPT score showed a moderate discriminative power in predicting major bleeding events at 1 year (pooled c-stat: 0.71; 95% CI: 0.64-0.77).</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis confirms the external validity of the PRECISE-DAPT score in predicting out-of-hospital bleeding outcomes in patients on DAPT following PCI. The moderate discriminative ability highlights the need for future improved risk prediction tools in the field.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076022","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":"What is new in the 2023 AHA/ACC multisociety guideline on chronic coronary disease?","authors":"Felice Gragnano, Vincenzo De Sio, Paolo Calabrò","doi":"10.1093/ehjcvp/pvad066","DOIUrl":"10.1093/ehjcvp/pvad066","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363132","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}
Maxim Grymonprez, Laura Carnoy, Andreas Capiau, Koen Boussery, Els Mehuys, Tine L De Backer, Stephane Steurbaut, Lies Lahousse
{"title":"Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.","authors":"Maxim Grymonprez, Laura Carnoy, Andreas Capiau, Koen Boussery, Els Mehuys, Tine L De Backer, Stephane Steurbaut, Lies Lahousse","doi":"10.1093/ehjcvp/pvad070","DOIUrl":"10.1093/ehjcvp/pvad070","url":null,"abstract":"<p><strong>Aims: </strong>The clinical relevance of common pharmacokinetic interactions with non-vitamin K antagonist oral anticoagulants (NOACs) often remains unclear. Therefore, the impact of P-glycoprotein (P-gp) and CYP3A4 inhibitors and inducers on clinical outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated.</p><p><strong>Methods and results: </strong>AF patients were included between 2013 and 2019 using Belgian nationwide data. Concomitant use of P-gp/CYP3A4-interacting drugs at the time of NOAC initiation was identified. Among 193 072 NOAC-treated AF patients, 46 194 (23.9%) and 2903 (1.5%) subjects concomitantly used a P-gp/CYP3A4 inhibitor or inducer, respectively. After multivariable adjustment, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding [adjusted hazard ratio (aHR) 1.24, 95% confidence interval (CI) (1.18-1.30)] and all-cause mortality risks [aHR 1.07, 95% CI (1.02-1.11)], but not with thromboembolism in NOAC-treated AF patients. A significantly increased risk of major bleeding was observed with amiodarone [aHR 1.27, 95% CI (1.21-1.34)], diltiazem [aHR 1.28, 95% CI (1.13-1.46)], verapamil [aHR 1.36, 95% CI (1.03-1.80)], ticagrelor [aHR 1.50, 95% CI (1.20-1.87)], and clarithromycin [aHR 1.55, 95% CI (1.14-2.11)]; and in edoxaban [aHR 1.24, 95% CI (1.06-1.45)], rivaroxaban [aHR 1.25, 95% CI (1.16-1.34)], and apixaban users [aHR 1.27, 95% CI (1.16-1.39)], but not in dabigatran users [aHR 1.07, 95% CI (0.94-1.23)]. Concomitant use of P-gp/CYP3A4 inducers (e.g. antiepileptic drugs like levetiracetam) was associated with a significantly higher stroke risk [aHR 1.31, 95% CI (1.03-1.68)], but not with bleeding or all-cause mortality.</p><p><strong>Conclusion: </strong>Concomitant use of P-gp/CYP3A4 inhibitors was associated with higher bleeding and all-cause mortality risks in NOAC users, whereas the use of P-gp/CYP3A4 inducers was associated with higher stroke risks.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41118969","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}