Serelaxin reduced risk for death from causes other than HF

The reduction of CV-related and all-cause mortality risk among patients with acute HF treated with serelaxin was driven mostly by reduction in sudden cardiac death and death due to CV-related causes other than HF, according to recent results.

The researchers evaluated data from the double blind, prospective, multicenter RELAX-AHF study, which randomly assigned 1,161 patients with acute HF to placebo (n=580) or IV serelaxin (n=581; Novartis) for up to 48 hours, with follow-up for 180 days. Results from the trial indicated a significant reduction in the rate of CV-related and all-cause mortality among patients treated with serelaxin. In this analysis, the effect of serelaxin therapy was compared among patients who died during the trial, according to their cause of death.

“Understanding mode of death and timing of events in patients with HF can provide insight into the mechanism of treatment effect of novel therapies,” the researchers wrote. “… The current analysis suggests that the primary treatment effects of serelaxin were on other CV events and sudden death, rather than deaths from HF.”

Researchers observed 107 deaths, including 88 CV-related. The breakdown of mode of death was as follows: 35% from HF, 23% from sudden cardiac death, 24% from other CV issues and 18% from non-CV causes.

Researchers noted that the effect of serelaxin was most pronounced among those who died of CV-related issues other than HF or sudden cardiac death (HR=0.29; 95% CI, 0.12-0.73) or experienced sudden cardiac death (HR=0.46; 95% CI, 0.2-1.07). No significant effect from serelaxin was observed among patients who died due to HF or non-CV causes.

A sensitivity analysis in which deaths due to unknown causes were reclassified as sudden deaths yielded similar results, but serelaxin therapy became significantly associated with reduction in risk for sudden death (HR=0.49; 95% CI, 0.25-0.98). Assessment of deaths due to specific CV-related causes other than HF indicated that 1.5% of placebo recipients died of stroke vs. 0.2% of patients in the treated group.

Mihai Gheorghiade

The researchers tested for heterogeneity due to the small total number of deaths and were unable to eliminate the possibility that the effect of serelaxin on mode of death was due to chance (P=.08). They concluded that their results require further assessment in larger studies incorporating more events.

In a related editorial, Stephen J. Greene, MD, and Mihai Gheorghiade, MD, of the Center for Cardiovascular Innovation at Northwestern University Feinberg School of Medicine, wrote that there is need for “a nuanced understanding of the modes and temporal distribution of death and competing risks for post-discharge adverse events” among patients with HF. They added that the researchers offered novel insights into this issue, but also “remind us to reflect on the specific type and mechanism of adverse outcome being targeted with future hospitalized HF trials.”

“Aligning a therapy with a well-defined mechanism for benefit with the hospitalized HF subpopulation at heightened risk of a specific adverse event will maximize chances of identifying a treatment that improves post-discharge outcomes,” Greene and Gheorghiade wrote.

For more information:

Felker GM. J Am Coll Cardiol. 2014;64:1591-1598.

Greene SJ. J Am Coll Cardiol. 2014;64:1599-1601.

Disclosure: See the full study and editorial for relevant financial disclosures.