Renin-Angiotensin System Inhibition Effect on Post-MI Mortality and New-Onset Atrial Fibrillation

A retrospective observational cohort study reported in the Journal of the American Heart Association found that inhibition of the renin-angiotensin system (RAS) reduced the risk of mortality post-acute myocardial infarction (AMI) in patients with and without congestive heart failure (CHF).¹

In previous research involving patients with CHF and/or left ventricular dysfunction, inhibition of the RAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) decreased the risk of recurring AMI, hospitalization, and death.^2-4 In addition, these agents have been shown to have antiarrhythmic properties.⁵

Guidelines from the United States and Europe recommend RAS inhibition for this patient group and further suggest that it may prevent new-onset atrial fibrillation (AF).^6,7 

To elucidate the benefits of ACEI and ARB, the researchers investigated whether their use was associated with lower cardiovascular and all-cause mortality, stroke, and reinfarction in patients who were post-AMI with and without CHF and/or AF.

They further aimed to determine whether the risk of new-onset AF was lower with RAS inhibition in patients with no AF history or in-hospital AF diagnosis post-AMI. 

The final sample included 112,648 adult patients (median age, 72; 35.5% women) across 72 coronary care units in Sweden who had been admitted for a first AMI; 73.9% were treated with ACEI or ARB or both.

RAS inhibition was linked with a reduced 3-year risk of all-cause mortality in each of the study’s 4 subgroups:

• Patients with CHF and AF (n=11,489; hazard ratio [HR]: 0.75; 95% CI, 0.70-0.81)
• Patients with CHF without AF (n=31,676; HR: 0.65; 95% CI, 0.60-0.69)
• Patients with AF without CHF (n=10,066; HR: 0.82; 95% CI, 0.75-0.90)
• Patients without either CHF or AF (n=59,417; HR: 0.76; 95% CI, 0.72-0.81)

No association was observed between RAS inhibition and a lower 3-year risk of new-onset AF in patients with no history of AF and with CHF (HR: 0.96; 95% CI, 0.84-1.10) or without CHF (HR: 1.12; 95% CI, 1.02-1.22).

These results align with those of prior research, including the Survival and Ventricular Enlargement (SAVE) trial and the Valsartan in Acute Myocardial Infarction (VALIENT) trial, among others.^8,4

“The lower risk of mortality observed in our study, and in previous trials, might be a result of reduction in myocardial infarct expansion, ventricular remodeling, and ventricular dilatation observed with RAS inhibition,” the investigators wrote.

Disclosures: Dr Andell reports receiving speaker fees from AstraZeneca; Dr Spaak reports receiving honoraria from Abbott/AbbVie, MSD, AstraZeneca, and Bristol-Myers Squibb; and Dr Oldgren reports receiving consultant and lecture fees from Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb/Pfizer. 

References

1. Batra G, Lindhagen L, Andell P, et al. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction [published online March 20, 2017]. J Am Heart Assoc. doi:10.1161/JAHA.116.005165
2. Køber L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333(25):1670-1676. doi:10.1056/NEJM199512213332503
3. Torp-Pedersen C, Køber L. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. Lancet. 1999;354(9172):9-12. 
4. Pfeffer MA, McMurray JJV, Velazquez EJ, et al; for the Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893-1906. doi:10.1056/NEJMoa032292 
5. Khatib R, Joseph P, Briel M, Yusuf S, Healey J. Blockade of the renin-angiotensin-aldosterone system (RAAS) for primary prevention of non-valvular atrial fibrillation: a systematic review and meta analysis of randomized controlled trials. Int J Cardiol. 2013;165(1):17-24. doi:10.1016/j.ijcard.2012.02.009 
6. O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-425. doi:10.1161/CIR.0b013e3182742cf6 
7. Steg PG, James SK, Atar D, et al; for the Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-2619. doi:10.1093/eurheartj/ehs215 
8. Flather MD, Yusuf S, Køber L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet. 2000;355(9215):1575-1581.