Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction

Background: Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees. Methods: We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25–50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier. Results: Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group. Conclusion: Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (&lt;50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.</p

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention An Updated Network Meta-analysis

Importance: Antithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks. Objectives: To evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI. Data Sources: Online computerized database (MEDLINE). Study Selection: Five randomized studies were included (N = 11542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI). Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019. Main Outcomes and Measures: The primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE). Results: The total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor. Conclusions and Relevance: The findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI

Acute, periprocedural and longterm antithrombotic therapy in older adults

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults. © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved.info:eu-repo/semantics/publishedVersio

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction:Main results from the PREFER in AF Prolongation Registry

International audienceAbstract The management of patients with atrial fibrillation (AF) has rapidly changed with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs) and changes in the use of rhythm control therapy. The prevention of thromboembolic events European Registry in Atrial Fibrillation Prolongation Registry (PREFER Prolongation) enrolled consecutive patients with AF on NOACs between 2014 and 2016 in a multicentre, prospective, observational study with one-year follow-up, focusing on the time of introduction of NOACs. Overall, 3783 patients were enrolled, with follow-up information available in 3223 (85%). Mean age was 72.2 ± 9.4 years, 40% were women, mean CHA 2 DS 2 VASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHA 2 DS 2 VASc score ≥ 2. Rivaroxaban was used in half of patients, and dabigatran and apixaban were used in about a quarter of patients each; edoxaban was not available for use in Europe at the time. Major cardiovascular event rate was low: serious events occurred in 74 patients (84 events, 2%), including 24 strokes (1%), 62 major bleeds (2%), of which 30 were life-threatening (1%) and 3 intracranial (0.1%), and 28 acute coronary syndromes (1%). Mortality was 2%. Antiarrhythmic drugs were used in about 50% of patients, catheter ablation in 5%. Adverse events were low in this contemporary European cohort of unselected AF patients treated with NOACs already at the time of their first introduction, despite high thromboembolic risk