Angiotensin receptor blocker in patients with ST segment elevation myocardial infarction with preserved left ventricular systolic function: prospective cohort study

I read the article by Yang JH,et al with great interest, in which the authors compared 1-year prognostic impacts of angiotensin receptor blockers (ARBs) with angiotensin converting enzyme inhibitors (ACEIs) in patients with ST segment elevation myocardial infarction (STEMI) with preserved left ventricular systolic function who underwent primary percutaneous coronary intervention (PCI) [1]. I believe it would be appreciated if authors discuss the long-term survival benefit of ARBs before concluding that ARBs are as beneficial as ACEIs in STEMI patients with preserved left ventricular systolic function after PCI.

Although ARBs could be an alternative to ACEIs, a recent observational study using inverse probability of treatment weighting and propensity score matching methods revealed that patients treated with ACEIs had significantly lower long-term mortality compared with those treated with ARBs from 2 to 5 years after acute myocardial infarction [2]. This study also demonstrated that crude survival rates in patients with ARBs and without renin-angiotensin aldosterone system inhibitors were almost similar in the landmark analysis at 2-year time-point, which first made me suspicious about long term survival benefit of ARBs. If the drug continued to work and followed a proportional hazard assumption, survival difference between patients with and without the drug is supposed to increase continuously.

Thus, the above phenomenon can be explained by the possibility that ARBs lost survival benefit with long-term usage which might result in the change of hazard at 2-year time-point in that observational study. I completely understand that this study does not give us conclusive statement because this is just an observational study using information at discharge without any dosage or adherence information and is not a randomized controlled trial. However, a meta-analysis enrolling 26 randomized controlled trials and total of 108,212 patients at high cardiovascular risk without heart failure revealed that only ACEIs, but not ARBs, reduced the risk of all-cause death in the primary prevention setting [3].

I believe that these studies raise a new concern about the long-term survival benefit of ARBs in my opinion. To the best of my knowledge, however, this kind of concern has never been discussed elsewhere. Although direct comparison between patients with ARBs and placebo in high risk patients for cardiovascular disorder could not be performed due to ethical problem in a recent evidence based medicine era, further evaluation of this problem should be performed and mandatory if we continue to use ARBs in clinical practice. That’s why I believe it would be appreciated if the authors discuss the long-term survival benefit of ARBs before concluding that ARBs are as beneficial as ACEIs in STEMI patients with preserved left ventricular systolic function after PCI.

1. Yang JH,et al.Angiotensin receptor blocker in patients with ST segment elevation myocardial infarction with preserved left ventricular systolic function: prospective cohort study. BMJ. 2014;349:g6650.
2. Hara M, et al. Comparison of 5-year survival after acute myocardial infarction using angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker. Am J Cardiol in press. (doi: 10.1016/j.amjcard.2014.03.055)
3. Savarese G, et al. A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure. J Am Coll Cardiol 2013;61:131-142.