A study published in Nature Medicine evaluated whole-exome sequencing data from the DECLARE-TIMI 58 clinical trial to determine whether sodium–glucose cotransporter 2 (SGLT2) inhibition is beneficial to patients with rare variants in cardiomyopathy-associated genes. The study included adults with type 2 diabetes and increased cardiovascular risk who were randomized to treatment with dapagliflozin or placebo.
Dapagliflozin is an SGLT2 inhibitor that has been shown to prevent hospitalization for heart failure due to left ventricular ejection fraction in patients with type 2 diabetes with, or at high risk for, atherosclerotic cardiovascular disease.
In this analysis, pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for heart failure were compared between carriers and noncarriers.
Whole exomes were evaluated in a total of 12,685 participants from the DECLARE-TIMI 58 trial and 121 carriers of CMP-associated variants were identified. This included 76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy.
Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of hospitalization due to heart failure more strongly in carriers than in noncarriers. Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers. Most carriers (82%) had no prior heart failure, and in carriers without prior heart failure, treatment with dapagliflozin reduced the absolute risk of hospitalization due to heart failure by 12.8%, compared to 0.6% in noncarriers.
The findings from this cohort may suggest that SGLT2 inhibitor treatment should be started early to prevent heart failure in individuals who carry P/LP cardiomyopathy variants.
To learn more about rare heart conditions, visit https://checkrare.com/diseases/heart-diseases/
