Evidence-based medications likely contributed to decreased rates of sudden death in heart failure
A meta-analysis showed that the rate of sudden death in HFrEF patients has fallen over the past two decades, suggesting a cumulative benefit of evidence-based medications on sudden death.Shen L, Jhund PS, Petrie MC, et al. - N Engl J Med 2017; 377:41-51
A meta-analysis showed that the rate of sudden death in HFrEF patients has fallen over the past two decades, suggesting a cumulative benefit of evidence-based medications on sudden death.
- Out of 40,195 eligible patients, 77% were men, 62% had an ischemic cause of HF and 8.9% died suddenly.
- The annual rate of sudden death fell over time, from 6.5% in the earliest trial (RALES, completed in 1998) to 3.3% in the most recent trial (PARADIGM-HF, completed in 2014). The P value for trend was 0.02.
- An exception to the fall of sudden death rates over time was the CORONA trial (completed in 2007), with a rate of sudden death of 5.2%. In this study the rate of death from any cause was also outside the declining trend for other trials, probably because only patients ≥60 years with ischemic HF were enrolled.
- The rate of sudden death was lower in the experimental-therapy groups than in the control groups in all the trials, with the exceptions of Val-HeFT and GISSI-HF. With adjustment for randomized group (groups combined per study), with the trial as a random effect, there was a decline in risk of sudden death of 44% over the 19 years (HR 0.56, 95% CI 0.33-0.93, P=0.03).
- The reduction in risk over time was attenuated with further adjustment for baseline covariates (adjusted HR 0.90, 95% CI 0.61-1.32, P=0.60), although the randomized group remained associated with a lower risk of sudden death (HR 0.86, 95% CI 0.81-0.92, P<0.001).
- At 90 days after randomization, the cumulative incidence rates of sudden death ranged from 2.4% (95% CI 1.6-3.1) in RALES to 1.0% (95% CI 0.8-1.3) in the PARADIGM-HF trial. In each trial, the cumulative incidence of sudden death at 180 days was approximately double that at 90 days, with a similar general trend towards lower rates in more recent trials.
- The cumulative risk of sudden death during follow-up increased significantly according to the length of time between the diagnosis of HF and randomization in the nine trials that had this information available (31,866 patients; 79% of the total study sample).
- In each trial, a higher rate of sudden death was observed in the subgroup of patients with a lower ejection fraction.
In a meta-analysis of 12 randomized trials, the rate of sudden death in HFrEF patients has fallen over the past two decades and the absolute rate of sudden death was lower among patients with a more recent diagnosis of HF. These findings suggest that there is a cumulative benefit of evidence-based medications on sudden death.