Cardio Trial Files: Vutrisiran in ATTR-CM, Asundexian vs. Apixaban in AFib, and Tirzepatide in HF & Obesity
Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy
Fontana M et al. NEJM (August 2024)
Bottom Line: This double-blind, randomized trial evaluated the efficacy and safety of vutrisiran, a subcutaneously administered RNA interference therapeutic agent, in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). A total of 655 patients were assigned to receive vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The primary outcome was a composite of death from any cause and recurrent cardiovascular events, with secondary outcomes including death from any cause, change in distance covered on the 6-minute walk test, and change in Kansas City Cardiomyopathy Questionnaire-Overall Summary score. Vutrisiran treatment resulted in a lower risk of death from any cause and recurrent cardiovascular events compared to placebo, as well as preserved functional capacity and quality of life. The incidence of adverse events was similar in both groups.
Asundexian versus Apixaban in Patients with Atrial Fibrillation
Piccini JP et al. NEJM (September 2024)
Bottom Line: This phase 3, international, double-blind trial compared the efficacy and safety of Asundexian, an activated factor XI (XIa) inhibitor, to standard-dose apixaban in high-risk patients with atrial fibrillation. The primary efficacy objective was to assess whether asundexian was at least noninferior to apixaban in preventing stroke or systemic embolism, while the primary safety objective aimed to determine if asundexian was superior to apixaban in reducing major bleeding events. The sample size was 14,810 patients with a mean age of 73.9 years and a mean CHA2DS2-VASc score of 4.3. Asundexian was found to be associated with a higher incidence of stroke or systemic embolism compared to apixaban (1.3% vs. 0.4%), but with fewer major bleeding events. The study was stopped prematurely at the recommendation of the independent data monitoring committee. Overall, the results suggest that Asundexian may not be as effective as apixaban in preventing strokes in this patient population.
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
Packer M et al. NEJM (November 2024)
Bottom Line: This international, double-blind, randomized, placebo-controlled trial evaluated the effects of tirzepatide on cardiovascular outcomes in patients with heart failure with preserved ejection and obesity. A total of 731 patients were randomly assigned to receive either tirzepatide or placebo for at least 52 weeks. The primary outcome was a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event, and the secondary outcome was the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). The results showed that tirzepatide led to a lower risk of the primary outcome compared to placebo (9.9% vs. 15.3%), while also improving health status. Adverse events, primarily gastrointestinal, led to trial drug discontinuation in 6.3% of patients in the tirzepatide group and 1.4% in the placebo group.
Cardio Trial Files Issue #CRD-2025-04
Want to view past issues? Visit our archive:
