Editor—We agree with Verma and Strauss that it is naive to consider that angiotensin receptor blockers are like angiotensin converting enzyme (ACE) inhibitors, but without the cough.1 Although the evidence is conflicting, the hypothesis that angiotensin receptor blockers may predispose to myocardial infarction when used in preference to ACE inhibitors warrants further attention.
Long term clinical benefits of treatment with ACE inhibitors, including reduction in fatal and non-fatal myocardial infarction, are well established in chronic heart failure, hypertension, and after myocardial infarction.2 These benefits persist, although serum concentrations of angiotensin II return to pre-treatment values after long term treatment with ACE inhibitors.3
This implies that the mechanism(s) of benefit from ACE inhibitors extend beyond simple antagonism of angiotensin II. The effects of ACE inhibitors are related to the upstream blockade of the renin-angiotensin axis, which not only attenuates the conversion of angiotensin I to angiotensin II but also inhibits the degradation of kinins to inactive metabolites. ACE inhibitors, and not angiotensin receptor blockers (which block the renin-angiotensin axis at its most distal, type I receptor site), therefore result in raised concentrations of bioactive kinins such as bradykinin.4
This fundamental difference is important since bradykinin has several beneficial actions—antiarrhythmic effects and reduction of infarct size mediated through ischaemic preconditioning and vascular protection mediated by nitric oxide or prostacyclin.4 In addition, the hypothesis has some rationale that angiotensin II type II receptors, as well as the type I receptors, may have potentially deleterious effects in cardiovascular disease.5
The cautions voiced by Verma and Strauss are biologically credible, and we therefore advise that until these issues are resolved, angiotensin receptor blockers should be used with caution in subjects who are perceived to be at a high coronary risk.
Competing interests: None declared.
References
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