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Original Investigation
July 22, 2020

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial

Author Affiliations
  • 1The George Institute for Global Health, The University of New South Wales, Sydney, Australia
  • 2The George Institute for Global Health, New Delhi, India
  • 3Clinical Trials Unit, Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka
  • 4Division of Dentistry, Division of Medical Education in English, Department of Population Medicine and Civilization Diseases Prevention, Faculty of Medicine, Medical University of Bialystok, Bialystok, Poland
  • 5All India Institute of Medical Sciences, New Delhi, India
  • 6Department of Epidemiology and Biostatistics, The University of Auckland, Auckland, New Zealand
  • 7Centre for Chronic Disease Control and Public Health Foundation, New Delhi, India
JAMA Cardiol. 2020;5(11):1219-1226. doi:10.1001/jamacardio.2020.2739
Key Points

Question  What is the association of a triple pill containing low doses of 3 antihypertensive medications with therapeutic inertia compared with usual care?

Findings  In this secondary analysis of a randomized clinical trial including 700 patients with mild to moderate hypertension, rates of therapeutic inertia were significantly different between those in the triple pill group and those in the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]) and the week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]). Compared with those in the usual care group, significantly more patients in the triple pill group achieved blood pressure targets (221 of 318 [69.5%] vs 182 of 329 [55.3%]) with significantly fewer unique antihypertensive treatment regimens (23 vs 54 per 100 treated patients).

Meaning  Use of a low-dose triple combination antihypertensive medication improves blood pressure control and simplifies treatment regimen but is associated with increased therapeutic inertia.


Importance  Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia.

Objective  To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care.

Design, Setting, and Participants  A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019.

Interventions  Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care.

Main Outcomes and Measures  Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression.

Results  Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001).

Conclusions and Relevance  Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy.

Trial Registration  ANZCTR Identifier: ACTRN12612001120864