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Updated: Dec 25, 2025

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
[Prescription of fixed dose combinations of antihypertensive drugs]
Stéphane Laurent1, Theodora Bejan-Angoulvant2, Pierre Boutouyrie1
1Service de pharmacologie, Hôpital européen Georges-Pompidou, AP-HP, Inserm U 970, Paris, France.
Abstract:
PRESCRIPTION OF FIXED DOSE COMBINATIONS OF ANTIHYPERTENSIVE DRUGS. Many fixed-dose antihypertensive combinations are available for treating hypertension. Compared to free associations, fixed-dose combinations have major advantages including a well-defined dose-ratio and a better adherence. The later leads to higher antihypertensive efficacy and faster blood pressure lowering effect, particularly interesting in patients at high cardiovascular risk, and to a lower cost of global medical care. However, fixed-dose combinations have some theorical limitations that need to be evaluated in clinical practice: a reduced detection of the possible inefficacy of one of the medications, a reduced possibility of combining different dosages, an increased risk of misuse, and a higher risk of complications in case of non-adherence. Fixed-dose combination therapies are insufficiently prescribed for first-line antihypertensive treatment despite an increasing level of evidence and their recommendations by learned societies. Triple fixed-dose combinations, prescribed as second-line antihypertensive treatment, are not yet reimbursed by health care systems. Drug companies should be encouraged to perform large randomized controlled clinical trials, in order to demonstrate that fixeddose combination therapies, prescribed first-line, increase short and long-term adherence compared to free associations, and thus lower blood pressure to a higher extent, ultimately leading to a lower incidence of cardiovascular complications.
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