Physicians' Academy for Cardiovascular Education

Quarter-dose combinations BP-lowering medications improve management hypertension

Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering Agents

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Literature - Bennett A, Chow CK, Chou M, et al. - Hypertension. 2017;70:85-93

Main results


In a meta-analysis of 42 randomized studies, dual quarter-dose combinations of BP-lowering agents were as effective as standard-dose monotherapy with fewer side effects. Moreover, a quadruple quarter-dose combination treatment was twice as efficacious as standard-dose monotherapy. Quarter-dose combinations could improve the efficacy and tolerability of BP–lowering therapy.

Editorial comment

In their editorial article [6], Grassi and Mancia emphasize the unmet medical need for more effective BP-lowering therapies: ‘…BP control may not be easily achievable even when optimal treatment is used, as exemplified by the frequent inability to meet this goal also in randomized trials despite large use of combination treatment and environmental conditions that minimize therapeutic inertia and maximize treatment adherence.’

They also discuss the limitations of the meta-analysis of Bennet et al:

  • the quadruple quarter dose combination treatment results are based on a single study with a small sample size
  • the on-treatment duration was on average short
  • there are no data on the effects of a quarter dose triple combination

The authors conclude: ‘Finally, it would be important to expand the information provided by the meta-analysis of Bennett et al to ambulatory or home BP to see whether the remarkable ability of the quarter dose combination treatment to lower BP is consistent over the 24 hours or the low dose attenuates the effect at times farther from the drug administration or in conditions in which treatment has to successfully oppose the effect of pressure influences. These limitations, however, do not detract from the interest of the study data and their favourable clinical implications.’


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