National guidelines for the management of absolute cardiovascular disease risk

To the Editor: Concerns have been raised that the national Guidelines for the management of absolute cardiovascular disease risk1 recommend combining an angiotensin-converting enzyme (ACE) inhibitor with an angiotensin receptor blocker (ARB) for blood pressure reduction.2 Grenfell replied on behalf of the National Vascular Disease Prevention Alliance, stating that these agents are of the same pharmacological class3 and that the guidelines recommend using an agent from a different pharmacological class for second-line therapy. Therefore, he argued that the guidelines recommend “against prescribing” these agents in combination.3 This is incorrect.

ACE inhibitors and ARBs are different classes of drugs.4 ARBs specifically inhibit the angiotensin II type 1 receptor whereas ACE inhibitors block production of angiotensin II. ACE inhibitors also degrade peptides such as bradykinin and substance P, which explains why cough and angioedema are frequently seen with ACE inhibitor therapy, but rarely with ARB therapy. This and other pharmacological differences have clinical implications. For example, ACE inhibitor-induced cough or angioedema does preclude the use of an ARB in the same patient.4 Similarly, one cannot assume these drug classes produce similar clinical outcomes in the absence of evidence.

Even if these drugs were of the same class, the current form of the guidelines only recommends which combination should be used for second-line therapy, not which combinations should be avoided.1 This is appropriate. Clinicians should not think ACE inhibitors and ARBs should never be combined. Rather, if the choice exists, a different combination should be chosen. Put another way, hypertension should not be inadequately treated just to avoid using this combination.4