Compliance with Antihypertensive Therapy

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco.

This article originally appeared in the June 2011 issue of Clinical Cardiology Alert. It was peer reviewed by Ethan Weiss, MD. Dr. Weiss is Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford is a speaker for Astra-Zeneca, and Dr. Weiss reports no financial relationships relevant to this field of study.

Source: Kronish IM, et al. Meta-analysis: Impact of drug class on adherence to antihypertensives. Circulation 2011;123:1611-1621.

Hypertension is usually asymptomatic, so adherence to drug therapy is an issue, especially if the drugs used cause symptoms. Thus, these investigators performed a meta-analysis of 17 studies that measured adherence to antihypertensive drugs based upon medication refill data in order to determine the adherence rate of different antihypertensive drug classes.

The selected studies involved more than 900,000 patients and showed a range of adherence values across drug classes from 28% to 65%. Angiotensin receptor blockers (ARBs) had the best adherence compared to all other classes (P < 0.05). Almost all studies showed a lower adherence to diuretics than all other classes (P < 0.05). The relative adherence of the drug classes from highest to lowest were ACE inhibitors, calcium blockers, and beta-blockers. Various analytic methods were used that did not change the overall results, but the statistical significance between ARBs and angiotensin-converting enzyme (ACE) inhibitors or between diuretics and beta-blockers was lost with some analyses. The authors concluded that there are important differences in adherence to antihypertensive therapy by drug classes with the highest rate of adherence in renin-angiotensin system blockers and the lowest in beta-blockers and diuretics. However, even the best adherence rates observed were suboptimal in these trials.


In hypertension, compliance with antihypertensive drugs is the key to effective treatment. This may explain why treatment based on renin-angiotensin system blockers and calcium antagonists have shown better outcomes than those based upon beta-blockers and diuretics. There may be several reasons for these observed differences in compliance with drug therapy, but the most obvious is adverse effects. The drugs with the least adherence have the most side effects and vice versa. The high adherence drugs are the newest drugs, so some have claimed there is a physician bias toward heavily marketed drugs. As this study shows, patients vote with their adherence rate and these new drugs just have lower side effects. In fact, in the outpatient setting, I always start with an ARB because I do not want 10% of my patients stopping therapy because of ACE inhibitor cough.

There are limitations to this study. ARBs were the least prescribed drug; probably because until recently there was no generic one available in the United States. This may have biased the results in favor of ARBs. Not all drug classes were studied (e.g., alpha blockers). The study does not address the current recommendations and practice of initially prescribing drug combinations, especially in patients with very high blood pressures. Almost every combination of two antihypertensive drugs are available now in one tablet with a few tablets containing three drugs. Of course cost continues to be an important factor in patients' preference for drugs, but interestingly the relative costs of the drugs in this study did not seem to affect adherence significantly.