Abstract / Summary
Although the beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit in carriers of rare variants in cardiomyopathy-associated genes. Here we evaluated whole-exome sequencing data from the randomized DECLARE-TIMI 58 trial, in which adults with type 2 diabetes and increased cardiovascular risk were randomized to dapagliflozin or placebo treatment. Pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for HF (HHF) were compared between carriers of such variants and noncarriers. Among 12,685 patients for whom sequence data were obtained, 121 carried a cardiomyopathy variant (76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy). Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of HHF more strongly in carriers (hazard ratio 0.18, 95% confidence interval 0.04-0.86) than in noncarriers (hazard ratio 0.70, 95% confidence interval 0.57-0.86; P interaction 0.03). Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers (P interaction 0.03). Most carriers (82%) had no prior HF, and in carriers without prior HF, treatment with dapagliflozin reduced the absolute risk of HHF by 12.8%, compared with a reduction of 0.6% in noncarriers (P interaction 0.01). The findings from this cohort of older and high-risk patients raise the possibility that SGLT2 inhibitor treatment should be started early to prevent HF in individuals who carry P/LP cardiomyopathy variants. These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants.
Primary Source
Nature medicine
Ask Prognia AI
Have questions about this randomised trial?
Prognia AI can search this source alongside 35M+ PubMed papers and current ESC, AHA, NICE, and ADA guidelines to give you a fully cited clinical answer.
Related Clinical Guidelines
Related Blog Posts
ESC 2023 Heart Failure Guidelines: What Every Cardiologist Needs to Know
The 2023 focused update to the ESC Heart Failure Guidelines introduced key changes to SGLT2 inhibitor recommendations, HFmrEF management, and device therapy thresholds. Here is a practical summary.
CHADS₂-VASc in Practice: When to Start Anticoagulation in AF
A practical walkthrough of the CHADS₂-VASc scoring system, its ESC guideline thresholds, and how to use it alongside HAS-BLED to counsel patients with atrial fibrillation.