Small Subgroup Analysis Finds Stronger Heart-Failure Risk Reduction With Dapagliflozin in Cardiomyopathy Variant Carriers
A Nature Medicine analysis of the DECLARE-TIMI 58 trial found dapagliflozin produced an eightfold greater reduction in heart failure hospitalization among carriers of cardiomyopathy-linked genetic variants than among non-carriers.
medpagetoday.comA study published in Nature Medicine found that the diabetes drug dapagliflozin lowered hospitalization for heart failure about eight times more strongly in carriers of rare genetic variants linked to cardiomyopathy than in non-carriers. Researchers from Harvard Medical School, Mass General Brigham and MIT conducted the analysis using data from the DECLARE-TIMI 58 trial.
The trial enrolled more than 12,000 adults with type 2 diabetes and increased cardiovascular risk.
About 121 participants carried inherited gene variants that could raise their chances of developing cardiomyopathy. 2 years. 8 percent in the placebo group developed heart failure.
No heart-failure events occurred among carriers who received dapagliflozin. "Historically, identifying a genetic variant for cardiomyopathy mostly meant telling a patient they were at high risk and not having a specific preventive therapy to offer," said Shinwan Kany, MD, a visiting scientist at the Cardiovascular Research Center with Mass General Brigham Heart and Vascular Institute and the Broad Institute.
" Freeman noted that the results are an analysis of a larger randomized trial and require further confirmation.
He added that the narrow sample size of carriers also poses a limitation. Freeman said participants with no history of heart failure who took dapagliflozin were less likely to develop the condition, raising the possibility that SGLT2 inhibitors may be especially useful as preventive therapy in genetically high-risk individuals.
" SGLT2 inhibitors are already foundational cardiovascular and kidney-protective medications, Freeman said.
They reduce heart failure hospitalization across a broad range of patients, including those with diabetes, chronic kidney disease and established heart failure. Genetic testing for cardiomyopathy is often used for diagnosis, family screening and risk stratification, Freeman said.
If future clinical trials confirm the findings, cardiologists could eventually use genetic screening to identify high-risk patients, monitor them more closely, and begin treatments such as SGLT2 inhibitors before heart failure symptoms appear.
Heart failure does not always begin when symptoms appear, Freeman noted. In some patients, risk may be present years earlier due to inherited genetics. The decision to medicate should always be discussed with a clinician, especially for those with a personal or family history of cardiovascular events, he said.
