Circulation. 2021 Apr 9. doi: 10.1161/CIRCULATIONAHA.121.053659. Online ahead of print.
Background: Patients with heart failure and reduced ejection fraction (HFrEF) will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (i.e. first and repeat) hospitalizations for heart failure in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods: The total number of HF hospitalizations and cardiovascular deaths was examined using the proportional rates approach of Lei-Wei-Ying-Yang (LWYY) and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable LWYY model. Results: Of 2371 participants randomized to placebo, 318 experienced 469 hospitalizations for heart failure among; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher NT-proBNP and NYHA class. In the LWYY model the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or CV death was 0.75 (95%CI 0.65-0.88), p=0.0002. In the joint frailty model, rate ratio for total HF hospitalizations was 0.71 (95% CI 0.61-0.82), p<0.0001 while for cardiovascular death the hazard ratio was 0.81(95%CI 0.67-0.98), p=00282. Conclusions: Dapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03036124.