JAMA
Published online 28 May 2026 · Network Meta-Analysis
Adverse Effects and Treatment Discontinuation of Blood Pressure–Lowering Drugs and Combinations: A Network Meta-Analysis
Nelson Wang, Stephen Van Der Hoorn, Rashmi Pant, et al. — JAMA, 2026
Key Finding
In a network meta-analysis of 716 randomised trials (159,362 participants), ARB-containing regimens had fewer treatment discontinuations due to adverse effects than placebo. The ARB + calcium channel blocker combination showed the best overall tolerability profile. ACE inhibitor–containing regimens carried higher discontinuation rates (predominantly cough), while CCB monotherapy showed increased AE-related withdrawal vs. several combination arms.
Why This Paper Matters
Antihypertensive adherence is the single largest modifiable predictor of blood pressure control at the population level — and tolerability is its chief determinant. This is the most comprehensive network meta-analysis of AE-driven discontinuation to date, spanning 5 drug classes individually and in combination across a mean baseline BP of 158/100 mmHg. The finding that ARB + CCB combinations outperform monotherapy on tolerability — not just efficacy — directly supports combination-first prescribing strategies. For pharmacologists, the ARB vs ACEi tolerability gap (driven by bradykinin-mediated cough with ACEi) is a classic mechanism-to-outcome translation: this paper quantifies it at scale.
Antihypertensives
ARB · ACEi · CCB · Beta-blocker · Thiazide
Adherence & Tolerability
Network Meta-Analysis
716 RCTs · 159,362 patients
JAMA 2026
💊 Prescriber's Note
ARB + CCB as a combination has mechanistic synergy too: ARBs block Ang II–mediated vasoconstriction and aldosterone release; CCBs reduce peripheral vascular resistance independently. The absence of ACEi-associated bradykinin accumulation with ARBs eliminates the cough-dropout problem entirely — this paper gives you the NMA-level evidence to back that switch when a patient reports cough on ramipril or enalapril.
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