A network meta-analysis of the discontinuation of blood-pressure (BP)-lowering medications due to adverse drug effects (AEs) found that the best-tolerated treatment was a combination of an angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), with four of the top five best-tolerated regimens containing ARBs, according to research published May 28 in JAMA.

The meta-analysis included 716 short-term double-blind, randomized clinical trials identified from the Cochrane Central Register of Controlled Trials, MEDLINE and Epistemonikos comprising nearly 160,000 adults who received placebo or antihypertensive therapy from five major classes: ACE inhibitors, ARBs, beta-blockers, CCBs, and diuretics (thiazide and thiazide-like, mineralocorticoid receptor agonists and others) and their combinations, over a duration of four to 26 weeks. The patients were 55 years old and 44% were women; their mean baseline BP was 158/100 mm Hg.

Results over the mean follow-up of 8.6 weeks showed that two treatment regimens were associated with a lower risk of treatment discontinuation due to AEs (ARB + CCB [odds ratio [OR], 0.61] and ARB monotherapy [OR, 0.73], compared with placebo (risk difference [RD] of –1.2% and –0.8%, respectively. In contrast, three treatment regimens, compared with placebo, were associated with a higher risk of AE-related treatment discontinuation: CCB monotherapy (OR, 1.43; RD, 1.2%), ACE + CCB (OR, 1.46; RD, 1.1%) and beta-blocker + thiazide diuretics (OR, 1.58; RD, 1.7%).

Ranked in order, the five best tolerated drug classes and combinations were: ARB + CCB, ARB + beta-blocker, ARB monotherapy, CCB + thiazide diuretic and ARB + thiazide diuretic – with all ARB-containing regimens associated with less treatment discontinuation.

Overall, five combination and two monotherapy regimens had higher surface under the cumulative ranking curve values than placebo, "suggesting overall symptomatic improvement," according to analysis authors Nelson Wang, PhD, et al.

All treatment regimens significantly increased dizziness compared with placebo, with greater risk with combination vs. monotherapy. All but CCBs significantly decreased headache compared with placebo.

"A large proportion of treatment discontinuations due to AEs tend to occur during the first few months after treatment is started," write the authors on their focus on short-term trials. "Because patient-reported symptoms are common, clinicians are often faced with the challenge of determining whether symptoms are truly drug related or merely temporally associated with treatment initiation."

"Results from the study by Wang, et al., can help inform clinicians' selection of antihypertensive therapies for patients initiating medications for hypertension, particularly when comorbidities, such as the presence of diabetes with microvascular disease, do not warrant a specific therapy," write Mary M. McDermott, MD, and Stephen D. Persell, MD, MPH, in an accompanying editorial comment. They add that it should not prompt changes in patients already undergoing a stable, AE-free regimen.