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Updated: Mar 17, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
[Pharmaceutical intervention to reduce the iatrogenic risk associated with the triple whammy combination]
Gemma Arrufat-Goterris1, Fernando do Pazo-Oubiña1, María Malpartida-Flores2
1Hospital Universitario Son Espases, Palma de Mallorca, España.
Objective:
To analyze the effect of an intervention to reduce the iatrogenic risk associated with concomitant treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin-II receptor blockers (ARB) with diuretics and nonsteroidal anti-inflamatory drugs (NSAID), combination known as triple whammy (TW).
Design:
Uncontrolled before-after intervention study.
Location:
15 health centers from a health area (reference population of 292.746 habitants).
Participants:
260 patients ≥18 years old with chronic and concomitant prescriptions of drugs from the therapeutic groups (ATC code): diuretics (C03), ACEi/ARBs (C09) and NSAID (M01) during the month of January 2015 INTERVENTIONS: A double intervention was conducted during February and March 2015: an educational part, which consisted of an informative session, and an individualized part, in which recommendations to general practitioner were assessed after reviewing medical records.
Main Measurements:
The number of patients in whom at least one intervention was accepted and the number of patients who continued on TW combination in June 2015, were analyzed. Results were analyzed using descriptive statistics and the prevalence of TW was compared with the one in June 2015 using the Newcombe-Wilson's hybrid method.
Results:
260 patients were included in the study. Recommendations were made in 165 patients (63.5%) and at least one was accepted in 97 (58.8%) patients. In June 2015, 184 patients continued with the TW combination. The TW prevalence decreased by 0.19/1,000 patients (IC 95%: 0.04/1,000 to 0.34/1,000; P=0.017) after the intervention.
Conclusions:
The intervention improved the prescription and reduced the number of patients on TW combination.
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