Early Use of Sacubitril/Valsartan Linked to Improved Cardiac Function Post AMI

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Individuals with a history of acute myocardial infarction (AMI), or heart attack, may benefit on several fronts following early administration of the neprilysin inhibitor/angiotensin receptor blocker sacubitril/valsartan.

Individuals with a history of acute myocardial infarction (AMI), or heart attack, may benefit from early administration of the neprilysin inhibitor/angiotensin receptor blocker (ARB) sacubitril/valsartan through decreased hospitalization risk, improved cardiac function, and reversal of left ventricular (LV) remodeling.

Study findings were recently published in ESC Heart Failure.

“Almost 25% of AMI patients develop heart failure,” the authors wrote. “Besides timely revascularization, regulating the neuroendocrine hormone balance is another pivotal way to improve their prognosis. Sacubitril-valsartan helps to promote vasodilation, natriuresis, and diuresis, along with inhibiting myocardial fibrosis and hypertrophy.”

The authors performed their systematic review and meta-analysis because data remain mixed on the use of sacubitril/valsartan compared with combination treatment of an angiotensin converting enzyme (ACE) inhibitor/ARB in patients following AMI. They searched for articles in the PubMed, Embase, Cochrane Library, and the China National Knowledge Infrastructure databases from inception through May 10, 2021, using the terms angiotensin-receptor neprilysin inhibitor, sacubitril-valsartan, LCZ696, MI, and AMI.

Their final analysis comprised 13 articles on randomized controlled trials (RCTs). This included 424 patients from 3 trials that investigated cardiac mortality and 1129 patients from 5 trials each that investigated rates of myocardial reinfarction (n = 469) and hospitalization for heart failure (n = 660).

In the first group of trials, significant differences in cardiac mortality were not seen between the sacubitril/valsartan and ACE inhibitor/ARB groups, whereas in the remaining 10 trials, although sacubitril/valsartan led to overall lower rates of hospitalization for patients with heart failure vs ACE inhibitor/ARB treatment, myocardial reinfarction rates did not significantly improve. In addition for these 10 trials, a subgroup analysis looked at sacubitril/valsartan vs ACE inhibitors and ARBs on an individual basis, and again showed sacubitril/valsartan’s superior ability to the 2 treatments at lowering hospitalization rates for heart failure.

Eleven of the 13 studies also contained data on N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels at last study visit, and this was always significantly lower in the sacubitril/valsartan groups vs ACE inhibitors/ARB groups.


Left ventricular ejection fraction (LVEF) and LV end-diastolic dimension (LVEDD) were evaluated in 7 studies, and a random effects model showed that LVEF and LVEDD were significantly increased and reversed, respectively, following use of sacubitril/valsartan vs ACE inhibitors/ARBs. A subgroup analysis also showed that sacubitril/valsartan, vs an ACE inhibitor or ARB alone, improved LVEF.

“In summary, this meta-analysis suggests that early administration of sacubitril–valsartan may be superior to conventional ACE inhibitor/ARB to decrease the risk of hospitalization for HF, improve the cardiac function, and reverse the LV remodeling in AMI patients,” the authors concluded.

Use of sacubitril/valsartan was also shown to not increase risks of hypotension, hyperkalemia, angioedema, and cough, but it did significantly improve distance on the 6-minute walk test.

The PARADISE-MI study—a well-designed RCT with a large sample size—will be used to confirm their findings and further investigate possible long-term improvements among patients with a history of AMI following administration of sacubitril/valsartan.


Xiong B, Nie D, Qian J, et al. The benefits of sacubitril–valsartan in patients with acute myocardial infarction: a systematic review and meta-analysis. ESC Heart Fail. Published online October 30, 2021. doi:10.1002/ehf2.13677