Declines in cardiovascular death in HFpEF: individual participant-level data from 6 global trials spanning 1999 to 2023
M Gori, Y Hamatani, B Claggett, L Fazzini, M Senni, M Pfeffer, I Anand, J Mcmurray, P Jhund, A Akshay, E F Lewis, M Vaduganathan, S D SolomonAbstract
Background
Mortality patterns in heart failure with preserved ejection fraction (HFpEF) may be evolving due to changes in population demographics, comorbidity burden, and improved management of HF. We aimed to investigate trends in cause-specific mortality among patients enrolled in HFpEF randomized clinical trials over more than two decades.
Methods
We included individual-participant level data from 6 international randomized clinical trials enrolling patients with HFpEF from 1999 to 2023 (CHARM -Preserved, I-PRESERVE, TOPCAT-Americas, PARAGON-HF, DELIVER, and FINEARTS-HF). We examined the association between calendar year and the risk of each cause of death in a multivariable Cox model adjusted for demographics, comorbidities, LVEF, previous HF hospitalization, NTproBNP, and randomized treatment.
Results
The analysis included 25978 patients (mean age: 71±9 years, 48% women, mean LVEF: 56±9%). Over the past 25 years, the risk of cardiovascular death (CVD) has significantly declined (adjusted HR, 0.73; 95% CI, 0.60-0.89). Similar reductions in CVD were observed in the cohort restricted to LVEF>=50%. In contrast, infection-related mortality, including death during the COVID-19 pandemic, showed a marked increase (adjusted HR, 5.65; 95% CI, 3.66-8.73), whereas other non-CVD remained stable (adjusted HR, 0.97; 95% CI, 0.74-1.27). As a result, all-cause mortality (ACM) slightly increased across the included trials (adjusted HR, 1.18; 95% CI, 1.01-1.38) (Figure). Randomized treatment was associated with a significant reduction in CVD (adjusted HR, 0.90; 95% CI, 0.83-0.97).
Conclusions
Over the last 2 decades among participants with HFpEF enrolled in global clinical trials, CVD death has declined, which may in part be related to interval improvements in medical therapy. However, these temporal gains appear to have been offset by recent increases in infectious deaths in this population.Trends in mode of death in HFpEFFor image description, please refer to the figure legend and surrounding text.