ARB-Based Antihypertensive Regimens Show Superior Tolerability in Large Network Meta-Analysis
核心洞察
A network meta-analysis of 716 trials and nearly 160,000 adults found ARB + CCB combination therapy had the lowest risk of discontinuation due to adverse events (OR 0.61 vs. placebo).
ARB monotherapy was associated with 27% lower odds of AE-related discontinuation, while CCB monotherapy, ACE + CCB, and beta-blocker (搜索) + thiazide regimens showed higher discontinuation rates than placebo.
Four of the five best-tolerated regimens contained an ARB, with the top five being ARB + CCB, ARB + beta-blocker (搜索), ARB monotherapy, CCB + thiazide diuretic (搜索), and ARB + thiazide diuretic.
A comprehensive network meta-analysis published May 28 in JAMA has identified angiotensin receptor blocker (ARB)-based antihypertensive regimens as the best-tolerated options for blood pressure management, with the combination of an ARB and calcium channel blocker (CCB) ranking highest for minimizing treatment discontinuation due to adverse events.
The analysis, led by Nelson Wang, PhD, and colleagues, pooled data from 716 short-term double-blind, randomized clinical trials encompassing 159,362 adults who received placebo or antihypertensive therapy from five major drug classes: ACE inhibitors, ARBs, beta-blockers, CCBs, and diuretics (including thiazide, thiazide-like, and mineralocorticoid receptor agonists), along with their combinations. The mean follow-up was 8.6 weeks, with trial durations ranging from four to 26 weeks. Participants had a mean age of 55 years, 44% were women, and the mean baseline blood pressure was 158/100 mm Hg.
ARB-containing regimens dominate tolerability rankings
Compared with placebo, two treatment regimens demonstrated significantly lower risk of treatment discontinuation due to adverse events: ARB plus CCB combination therapy (odds ratio [OR], 0.61; risk difference [RD], −1.2%) and ARB monotherapy (OR, 0.73; RD, −0.8%). These findings translate to a 39% and 27% reduction in the odds of AE-related discontinuation, respectively.
In contrast, three regimens were associated with higher discontinuation risk compared with placebo: CCB monotherapy (OR, 1.43; RD, 1.2%), ACE inhibitor (搜索) plus CCB (OR, 1.46; RD, 1.1%), and beta-blocker (搜索) plus thiazide diuretic (搜索) (OR, 1.58; RD, 1.7%).
When ranked by overall tolerability, the five best-tolerated drug classes and combinations were: ARB plus CCB, ARB plus beta-blocker (搜索), ARB monotherapy, CCB plus thiazide diuretic (搜索), and ARB plus thiazide diuretic. Notably, four of the top five regimens contained an ARB, and all ARB-containing regimens were associated with less treatment discontinuation.
Symptom-specific findings
The analysis revealed nuanced patterns in specific adverse effects. All treatment regimens significantly increased dizziness compared with placebo, with combination therapy generally producing greater increases than monotherapy. Conversely, all drug classes except CCBs significantly decreased headache compared with placebo, and several combination therapies were associated with fewer headaches than their monotherapy counterparts.
Oedema occurred more frequently with CCB-containing regimens, while cough was most strongly associated with ACE inhibitor (搜索)-containing therapies—findings consistent with the known side-effect profiles of these drug classes.
Clinical implications for treatment initiation
The authors emphasized the clinical relevance of focusing on short-term trials. "A large proportion of treatment discontinuations due to AEs tend to occur during the first few months after treatment is started," they wrote. "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."
The study used treatment discontinuation due to adverse events as a measure of overall tolerability, capturing adverse effects that were sufficiently important to lead to treatment withdrawal. The authors noted that overall tolerability reflects the net balance of adverse and beneficial effects.
Five combination and two monotherapy regimens had higher surface under the cumulative ranking curve values than placebo, "suggesting overall symptomatic improvement," according to the analysis authors.
Direct pairwise analyses using US Food and Drug Administration approval data produced findings consistent with those of the primary network meta-analysis, strengthening confidence in the results.
Limitations and context
The analysis was based on trial-level rather than individual patient data, and follow-up was limited to four to 26 weeks, meaning the findings relate specifically to short-term tolerability rather than long-term treatment persistence. Nevertheless, the results address an important gap in the evidence base, as concerns about adverse effects are recognized as significant contributors to treatment inertia, reluctance to intensify therapy, and poor adherence—factors that help explain why hypertension (搜索) remains inadequately controlled in many patients despite widely available effective therapies.