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NEJM Evidence Feb 2024BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: In this international registry-based, randomized, double-blind trial, patients without prior diabetes or chronic heart failure, presenting with acute MI and impaired left ventricular systolic function, were randomly assigned 10 mg of dapagliflozin or placebo, given once daily. The primary outcome was the hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method. The key secondary outcome was the same hierarchical composite excluding the body weight component. RESULTS: We enrolled 4017 patients of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P<0.001). The win ratio outcome, which was adopted in a change of analysis during trial performance because of low event accrual, was mainly driven by the added cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure occurred in 50/2019 (2.5%) patients assigned to dapagliflozin and 52/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. CONCLUSIONS: In patients with acute MI as noted above, after approximately 1 year of treatment with dapagliflozin there were significant benefits with regard to improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure compared with placebo. (Funded by AstraZeneca; ClinicalTrial.gov number, NCT04564742.)
Topics: Humans; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Myocardial Infarction; Benzhydryl Compounds; Glucosides
PubMed: 38320489
DOI: 10.1056/EVIDoa2300286 -
American Heart Journal Dec 2023Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need.
METHODS
DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease ≥5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database.
CONCLUSIONS
The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT04564742.
Topics: Humans; Diabetes Mellitus, Type 2; Heart Failure; Benzhydryl Compounds; Myocardial Infarction; Stroke Volume
PubMed: 37648579
DOI: 10.1016/j.ahj.2023.08.008 -
Circulation Jul 2023Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible...
BACKGROUND
Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care.
METHODS
MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events.
RESULTS
At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHADS-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; =0.001). Acute major adverse events occurred in 1.9% of patients.
CONCLUSIONS
In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.
Topics: Humans; Female; Middle Aged; Aged; Atrial Fibrillation; Retrospective Studies; Stroke Volume; Ventricular Function, Left; Treatment Outcome; Atrial Flutter; Registries; Catheter Ablation; Recurrence; Pulmonary Veins
PubMed: 37199171
DOI: 10.1161/CIRCULATIONAHA.123.064959 -
European Journal of Heart Failure Jul 2023Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes.... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.
METHODS AND RESULTS
In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66-0.93] vs. 0.78 [0.64-0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57-0.94] vs. 0.72 [0.54-0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m /year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.
CONCLUSIONS
In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.
Topics: Humans; Heart Failure; Atrial Fibrillation; Stroke Volume; Ventricular Function, Left
PubMed: 37062866
DOI: 10.1002/ejhf.2861