Choosing the best first antihypertensive can often be determined by patient comorbidity. An ACE-inhibitor, for example, makes sense for diabetic patients who require renovascular protection or for the heart failure patient with ventricular remodeling. We may make selections based on convenience (i.e. beta-blockers not requiring laboratory follow-up compared to ACE-inhibitors). But for patients without any prevailing medical conditions, is one antihypertensive better than another?
Dr. Atle Fretheim of the University of Oslo, and colleagues, recently published a meta-analysis assessing the comparative effectiveness of different classes of antihypertensive drugs for reduction of incident cardiovascular events among healthy people at risk of cardiovascular disease. Drugs evaluated included diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACE-inhibitors), angiotensin receptor blockers (ARBs), and alpha-blockers.
Centers for Disease Control and Prevention
For patients without comorbidities, is one antihypertensive better than another?
Studies were included if they were randomized controlled trials comparing one or more drugs against each other, or no active treatment. Trials were excluded if more than half the participants had had a myocardial infarction, stroke or other significant cardiovascular event. The primary outcome of interest was cardiovascular morbidity or mortality. Twenty-five studies were included in the final analysis (BMC Med. 2012;10:33).
No clear winner emerged for outcomes of interest. But several interesting findings were suggested by this analysis. First, beta-blockers were associated with a higher risk of total mortality compared to ARBs (relative risk 1.14; 95% [credibility intervals] CrI: 1.02 to 1.28). Second, ACE-inhibitors increased the risk of stroke compared to CCBs (RR 1.19; 95% CrI 1.03 to 1.38). Third, ACE-inhibitors reduced the risk of heart failure compared to CCBs (RR 0.82; 95% CrI 0.69 to 0.94). Fourth, diuretics reduced the risk of MI compared to beta-blockers (RR 0.82; 95% CrI 0.68 to 0.98) and reduced heart failure compared to CCBs (RR 0.73; 95% CrI 0.62 to 0.84), beta-blockers (RR 0.73; 95% CrI 0.54 to 0.96) and alpha-blockers (RR 0.51; 95% CrI 0.40 to 0.64). Fifth, diuretics significantly increased the risk of diabetes relative to ACE-inhibitors (RR 1.43; 95% CrI 1.12 to 1.83) and CCB (RR 1.27; 95% CrI 1.05 to 1.57). Based upon this evidence the authors presented a ranking of the drug classes.
Some of us may still be unsure about which antihypertensive to prescribe – or to avoid – and whether these findings are relevant to clinical practice. The investigators leave us with potentially clinically useful guidance in this regard: beta-blockers (notably, all studies included atenolol) and alpha-blockers were the only drug classes not found to be significantly superior to any drug for any outcome. This suggests against recommending these two classes as first-line medications for primary prevention of cardiovascular disease.
Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He is an investigator on a clinical trial investigating the safety of varenicline. The opinions expressed are solely those of the author. Contact him at ebbert.jon@mayo.edu.