ATMOSPHERE: Aliskiren fails to benefit patients with HF, diabetes vs. enalapril

In patients with diabetes and HF, the direct renin inhibitor aliskiren did not significantly improve outcomes compared with the ACE inhibitor enalapril, according to new data from the ATMOSPHERE trial.

In the overall results, presented in April, aliskiren (Tekturna, Novartis) alone or combined with enalapril did not improve CV mortality or hospitalization for HF compared with enalapril alone.

Lars Køber, MD, consultant cardiologist at Rigshospitalet – Copenhagen University Hospital, Denmark, presented findings from a subgroup analysis of patients with diabetes at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure.

As a result of the ALTITUDE and ASTRONAUT trials, the European Medicines Agency ordered the ATMOSPHERE investigators to stop enrolling patients with diabetes and stop administering aliskiren to patients with diabetes already enrolled, according to the study background.

“The result may have been positive had the European Medicines Agency not asked us to withdraw patients with diabetes from the trial,” Køber said in a press release. “We will never know, as the angiotensin receptor-neprilysin inhibitor [sacubitril/valsartan; Entresto, Novartis] has since emerged and bypassed the need for aliskiren.”

Køber presented findings from the 1,944 patients with diabetes (mean age, 64 years; 22% women) enrolled in the trial. Because of the order from regulators, mean follow-up for patients with diabetes was 24.1 months compared with 46 months for patients without diabetes (P < .0001).

In the primary outcome of CV mortality or HF hospitalization for patients with diabetes, there was no significant difference between aliskerin alone and enalapril alone (HR = 0.827; 95% CI, 0.676-1.01) or between aliskiren plus enalapril and enalapril alone (HR = 0.859; 95% CI, 0.708-1.043), according to the researchers. However, they found, the point estimate was more favorable to the aliskerin groups in patients with diabetes than in patients without diabetes (HR for aliskerin vs. enalapril = 1.059; 95% CI, 0.946-1.185; HR for combination vs. enalapril = 0.957; 95% CI, 0.853-1.073), although the P value for interaction was not significant.

All-cause mortality in patients with diabetes was similar between the groups (HR for aliskiren vs. enalapril = 0.887; 95% CI, 0.698-1.126; HR for combination vs. enalapril = 0.866; 95% CI, 0.685-1.094).

Safety outcomes in patient diabetes were similar between aliskiren and enalapril except for aliskiren having a lower rate of symptomatic hypotension (6.7% vs. 10%; P = .04), the researchers reported.

“Aliskiren monotherapy looked promising in [patients with HF and diabetes], with an 18% almost significant reduction in [CV] death or [HF] hospitalization compared to enalapril,” Køber said in the release. “There was a lower rate of symptomatic hypotension and no increase in other adverse events. This suggests that aliskiren could be an alternative for patients who cannot tolerate an ACE inhibitor.” – by Erik Swain

Reference:

Køber L, et al. Late-Breaking Trials III: Focus on Trial Updates, Registries and Meta-Analyses. Presented at: Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure; May 21-24, 2016; Florence, Italy.

Disclosure : The study was funded by Novartis. Køber reports consulting for Novartis and Sanofi.