Introduction and methodsNews - Apr. 9, 2020
Benefit Of Dapagliflozin On First And Repeat Events In Patients With HFrEF In DAPA-HF
Presented at ACC.20 by Piotr Ponikowski, MD, PhD (Wroclaw, Poland)
The DAPA-HF study showed that the SGLT2 inhibitor dapagliflozin reduced the risk of CV death or worsening HF in patients with HFrEF, in a time-to-first event analysis. However, HF patients often undergo recurrent hospitalizations. Time-to-first event analyses ignore repeated hospitalizations. Furthermore, in a composite outcome of CV death or HF hospitalization, CV death occurring after a first HF hospitalization is ignored in a time-to-first event analysis. Time-to first event analyses may therefore not reflect the full burden of HF and may overestimate the treatment benefit if the treatment effect decreases over time or if a sub-group of patients had multiple recurrent events. This pre-specified secondary analysis of the DAPA-HF trial analyzed both first and repeat HF hospitalizations.
A total of 4744 patients were included in the DAPA-HF trial. Key inclusion criteria were symptomatic HF with EF ≤40%; NT-proBNP ≥600 pg/ml (if hospitalized for HF within the last 12 months ≥400 pg/mL; if atrial fibrillation/flutter ≥900 pg/mL). Patients were randomized to receive either dapagliflozin (10 mg once daily, n=2373) or placebo (n=2371). Median follow up was 18.2 months. The primary endpoint of CV death or worsening HF event (unplanned HF hospitalization or urgent HF visit requiring IV therapy) was reduced with dapagliflozin compared to placebo (HR 0.74, 95%CI: 0.65-0.85, P<0.001).
The current analysis investigated recurrent events in the DAPA-HF trial and analyzed a composite outcome of recurrent HF hospitalizations or CV death using the LWYY method, which is a semi-parametric proportional rates model. A joint frailty model was used to account for the semi-competing risk of CV death when estimating the treatment effect on HF hospitalizations. The marginal mean of the cumulative number of recurrent HF hospitalizations over time was calculated with death as terminal event.
- 548 Patients experienced at least one hospital admission. The total number of first and recurrent hospitalizations was 809. Patients with multiple hospitalizations tended to have more advanced HF with more comorbidities.
- Recurrent events analysis showed that dapagliflozin reduced not only first but also recurrent HF hospitalizations (RR 0.75, 95%CI 0.65-0.88, p=0.0002 for the composite outcome of recurrent HF hospitalizations or CV death using the LWYY method; RR 0.71, 95%CI 0.61-0.82, P<0.0001 for HF hospitalization using the joint frailty model; and RR 0.81, 95%CI 0.67-0.98, P=0.0282 for CV death using the joint frailty model).
- Absolute risk reduction (ARR) and number needed to treat (NNT) for CV death or HF hospitalization were more favorable in the recurrent events analysis (ARR 5.3 per 100 ppt-yr and NNT=19) compared with the time-to-first event analysis (ARR 3.9 per 100 pt-yr and NTT=26).
Over a follow-up of 18.2 months, 261 recurrent HF hospital admissions were reported, which is 32% of the total number of first and recurrent hospitalizations. Treatment with dapagliflozin reduced the risk of first and recurrent HF hospitalizations compared with placebo.
- Our coverage of ACC.20 is based on the information provided during the congress –