New England Journal of Medicine最新文献

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

Methods: In an international trial, we randomly assigned in a 1:1 ratio patients with previous myocardial infarction and clinically significant ventricular tachycardia (defined as ventricular tachycardia storm, receipt of appropriate implantable cardioverter-defibrillator [ICD] shock or antitachycardia pacing, or sustained ventricular tachycardia terminated by emergency treatment) to receive antiarrhythmic drug therapy or to undergo catheter ablation. All the patients had an ICD. Catheter ablation was performed within 14 days after randomization; sotalol or amiodarone was administered as antiarrhythmic drug therapy according to prespecified criteria. The primary end point was a composite of death from any cause during follow-up or, more than 14 days after randomization, ventricular tachycardia storm, appropriate ICD shock, or sustained ventricular tachycardia treated by medical intervention.

Results: A total of 416 patients were followed for a median of 4.3 years. A primary end-point event occurred in 103 of 203 patients (50.7%) assigned to catheter ablation and in 129 of 213 (60.6%) assigned to drug therapy (hazard ratio, 0.75; 95% confidence interval, 0.58 to 0.97; P = 0.03). Among patients in the catheter ablation group, adverse events within 30 days after the procedure included death in 2 patients (1.0%) and nonfatal adverse events in 23 patients (11.3%). Among the patients assigned to drug therapy, adverse events that were attributed to antiarrhythmic drug treatment included death from pulmonary toxic effects in 1 patient (0.5%) and nonfatal adverse events in 46 patients (21.6%).

Conclusions: Among patients with ischemic cardiomyopathy and ventricular tachycardia, an initial strategy of catheter ablation led to a lower risk of a composite primary end-point event than antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH2 ClinicalTrials.gov number, NCT02830360.).

Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.

Methods: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life).

Results: A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P = 0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group.

Conclusions: Treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity. (Funded by Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.).

Background: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, often fatal disease. Nexiguran ziclumeran (nex-z) is an investigational therapy based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease) targeting the gene encoding transthyretin (TTR).

Methods: In this phase 1, open-label trial, we administered a single intravenous infusion of nex-z to patients with ATTR-CM. Primary objectives included assessment of the effect of nex-z on safety and pharmacodynamics, including the serum TTR level. Secondary end points included changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, high-sensitivity cardiac troponin T levels, the 6-minute walk distance, and the New York Heart Association (NYHA) class.

Results: A total of 36 patients received nex-z and completed at least 12 months of follow-up. Of these patients, 50% were in NYHA class III and 31% had variant ATTR-CM. The mean percent change from baseline in the serum TTR level was -89% (95% confidence interval [CI], -92 to -87) at 28 days and -90% (95% CI, -93 to -87) at 12 months. Adverse events were reported in 34 patients. Five had transient infusion-related reactions, and two had transient liver-enzyme elevations that were assessed as treatment-related. Serious adverse events, most of which were consistent with ATTR-CM, were reported in 14 patients. The geometric mean factor change from baseline to month 12 was 1.02 (95% CI, 0.88 to 1.17) in the NT-proBNP level and 0.95 (95% CI, 0.89 to 1.01) in the high-sensitivity cardiac troponin T level. The median change from baseline to month 12 in the 6-minute walk distance was 5 m (interquartile range, -33 to 49). A total of 92% of the patients had either improvement or no change in their NYHA class.

Conclusions: In this phase 1 study involving patients with ATTR-CM, treatment with a single dose of nex-z was associated with transient infusion-related reactions and consistent, rapid, and durable reductions in serum TTR levels. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051.).

Background: Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking.

Methods: We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHA₂DS₂-VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation. Patients were randomly assigned in a 1:1 ratio to undergo left atrial appendage closure or receive oral anticoagulation. The primary safety end point, tested for superiority, was non-procedure-related major bleeding or clinically relevant nonmajor bleeding. The primary efficacy end point, tested for noninferiority, was a composite of death from any cause, stroke, or systemic embolism at 36 months. The secondary end point, tested for noninferiority, was major bleeding, including procedure-related bleeding, through 36 months.

Results: A total of 803 patients were assigned to undergo left atrial appendage closure, and 797 to receive anticoagulant therapy. The mean (±SD) age of the patients was 69.6±7.7 years, 34.1% of the patients were women, and the mean CHA₂DS₂-VASc score was 3.5±1.3. At 36 months, a primary safety end-point event had occurred in 65 patients (8.5%) in the left atrial appendage closure group (device group) and in 137 patients (18.1%) in the anticoagulation group (P<0.001 for superiority); a primary efficacy end-point event had occurred in 41 patients (5.3%) and 44 patients (5.8%), respectively (P<0.001 for noninferiority); and a secondary end-point event had occurred in 3.9% and 5.0% (P<0.001 for noninferiority). Complications related to the appendage closure device or procedure occurred in 23 patients.

Conclusions: Among patients who underwent catheter-based atrial fibrillation ablation, left atrial appendage closure was associated with a lower risk of non-procedure-related major or clinically relevant nonmajor bleeding than oral anticoagulation and was noninferior to oral anticoagulation with respect to a composite of death from any cause, stroke, or systemic embolism at 36 months. (Funded by Boston Scientific; OPTION ClinicalTrials.gov number, NCT03795298.).