Why Are We Still Prescribing Angiotensin-Converting Enzyme Inhibitors?

Franz H. Messerli, MD; Chirag Bavishi, MD, MPH; Sripal Bangalore, MD, MHA


Circulation. 2022;145(6):413-415. 

In This Article

Abstract and Introduction


The human understanding when it has once adopted an opinion (either as being the received opinion or as being agreeable to itself) draws all things else to support and agree with it.
—Sir Francis Bacon, 1620

Prospective randomized controlled trials remain the gold standard in medicine because, when well performed, they provide us with knowledge untainted by bias. However, their outcome can be unpredictable. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) comprising 15 245 patients unexpectedly fell short, documenting that the incidence of myocardial infarction (MI) was 19% more common in the valsartan arm than in the amlodipine arm. This happened at a time when, on the basis of the results of the HOPE trial (Heart Outcomes Prevention Evaluation), the cardioprotective benefit of angiotensin-converting enzyme (ACE) inhibitors was firmly established in the minds of clinicians. The failure of valsartan in reducing MIs compared with amlodipine in VALUE was blamed on the angiotensin receptor blockers (ARBs) as a class and led to the concept of an MI paradox associated with ARBs—despite lowering blood pressure, these drugs did not reduce or perhaps even increased the risk of MI.