Angiotensin Receptor Blockers Reduce Cardiovascular Events, Including the Risk of Myocardial Infarction

The So-Called Angiotensin Receptor Blocker/Myocardial Infarction Paradox

More than a decade ago, the 15 245–patient VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation),¹ designed to show “that for the same level of blood-pressure (BP) control, valsartan-based treatment would be superior to amlodipine-based treatment in reduction of cardiac morbidity and mortality,” unexpectedly fell short in that myocardial infarction (MI) was 19% more common in the valsartan arm than in the amlodipine arm. Because renin-angiotensin system inhibitors, specifically ACEIs, previously were documented to have cardioprotective properties, failure in doing so in VALUE was blamed on valsartan and the ARBs as a class. An accompanying editorial stating that ARBs “may increase MI—and patients may need to be told”² caused a tempest in the teapot and led to extensive scrutiny of outcome data with this drug class. Subsequently, a number of investigators have proposed the concept of an “MI paradox” associated with ARBs. There was little question that at the time, in 2004, the editorialists had a point. However, many more solid randomized trials have been completed with results published since then that gradually but relentlessly challenged the above point of view.³ In the following, we analyze in aggregate the evidence of the comparative efficacy and safety of ACEIs and ARBs. When we look at experimental data and cardiac surrogate end points such as regression of left …