Ace Inhibitors as good as Sacubitril/Valsartan in preventing CV events in MI with HF
Sacubitril/valsartan, the heart failure drugs did not significantly reduce the rate of cardiovascular death, heart failure hospitalization or outpatient heart failure requiring treatment in patients following acute myocardial infarction (AMI) compared with the ACE inhibitor ramipril, suggests a study presented at the American College of Cardiology's 70th Annual Scientific Session on May 15, 2021.
Previous studies have shown that the combination of sacubitril and valsartan was more beneficial than an ACE inhibitor for patients with symptomatic heart failure and reduced ejection fraction. To further evaluate the superiority of sacubitril and valsartan combination, Dr Marc Pfeffer and his team conducted a first large trial to examine whether sacubitril/valsartan can reduce heart failure and associated hospitalizations and deaths in patients post-heart attack who face a high risk of developing heart failure.
The PARADISE-MI trial was a multi-centre, randomized, double-blind, active-controlled, parallel-group phase 3 study. The researchers included a total of 5661 patients at high risk of cardiovascular death and heart failure and randomized them to receive sacubitril-valsartan 97 mg-103 mg twice a day (n = 2830) or the ACE inhibitor ramipril 5 mg twice a day (n = 2831). The patients were followed for 23 months. The primary endpoints of the study was a composite of cardiovascular death, heart failure hospitalization or the development of symptomatic heart failure. Secondary endpoints included cardiovascular death or first heart failure hospitalization.
Key findings of the study were:
- Upon analysis, the researchers found that the rate of the composite primary endpoint was 10% lower in patients taking sacubitril/valsartan compared with those taking ramipril, falling short of the prespecified threshold of a 15% reduction required to demonstrate statistically significant improvement.
- Upon analyzing the safety endpoints, the researchers found that the sacubitril/valsartan was well-tolerated, had a favourable safety profile.
- In secondary efficacy analysis, they found no significant difference favouring sacubitril-valsartan for cardiovascular death or first heart failure hospitalization (308 vs 335 events), heart failure hospitalization or outpatient heart failure (201 vs 237 events), cardiovascular death, nonfatal MI, or nonfatal stroke (315 vs 349 events), and all-cause death (213 vs 242 events).
- They noted that only the outcome of cardiovascular death and total hospitalizations for heart failure, MI, or stroke was significantly superior with sacubitril-valsartan (591 vs 692 events; hazard ratio 0.84).
- They also noted that nearly 80% of patients in both groups experienced adverse events, with a serious adverse event rate of about 40% in each. The most common adverse event was hypotension, which occurred in 28.4% taking sacubitril-valsartan and 22.0% taking ramipril.
"We found sacubitril/valsartan was as safe and well-tolerated as one of the best proven ACE inhibitors, even in an acutely ill population," Dr Pfeffer said. "This trial may not change guidelines, but it should make physicians even more comfortable using sacubitril/valsartan in their patients with heart failure."
For further information:
Pfeffer MA et al. Angiotensin Receptor NeprilysinInhibition (ARNI) Following Acute Myocardial Infarction: Primary Results of the PARADISE-MI Trial. Late-breaking Trials Session 402. Presented at the American College of Cardiology (ACC) Virtual Annual Scientific Session 2021 on 15 May 2021.
