Physicians' Academy for Cardiovascular Education

Quadpill lowers blood pressure

Small randomized, placebo-controlled crossover trial shows that pill containing four drugs at quarter-dose achieved blood pressure-lowering without additional side effects.

Literature - Chow CK, Thakkar J, Bennett A, et al. - Lancet. 2017 Feb 9, Epub ahead of print


Multiple large-scale population studies show poor blood pressure control in many patients receiving blood pressure-lowering therapy [1]. Monotherapy has, even at high doses, low potency [2]. Moreover, it has been shown that benefit is obtained after intensification of blood pressure-lowering [3,4]. These two observations highlight the importance of new treatment strategies that are more efficacious and still tolerable. In this regard, low-dose combination therapy is promising, however effects at ultra-low doses are uncertain.

To elucidate this, a small randomized trial evaluating a quadpill containing four common blood pressure-lowering medications was performed, as well as a systematic review of 36 quarter-dose blood pressure-lowering trials. In this study, efficacy and tolerability of ultra-low (quarter) dose combination therapy were assessed. The randomized trial (1:1) was double-blind placebo-controlled and crossover, including 18 untreated hypertensive Australian patients that completed the study and received either placebo or irbesartan, amlodipine, hydrochlorothiazide and atenolol, each at quarter dose. A 2-week washout period was in between two times 4-weeks of treatment.

Main results


This small, randomized, placebo-controlled crossover trial showed blood pressure-lowering when using a capsule containing four blood pressure-lowering drugs each at quarter-dose. Systematic reviewing of trials that used one or two drugs at quarter-dose, revealed similar findings of a large benefit without additional side effects. This novel approach need further study to assess the contributions of different components and the long-term efficacy and safety in a broader population.


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Find this article online at The Lancet

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