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

Abstract

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.

Figure 1.. Number of Unique Antihypertensive Regimens by Treatment Group and Follow-up Visit

During the 6-month study period, there were 23 unique drug and dose regimens (12 unique drug regimens) per 100 persons treated in the triple gill group and 54 unique drug and dose regimens (25 unique drug regimens) per 100 persons treated in the usual care group. The number of patients treated with any blood pressure–lowering drug was similar between groups (randomization: triple pill, 140 of 349 [40.1%]; usual care, 147 of 351 [41.9%]; week 6: triple pill, 331 of 339 [97.6%]; usual care, 341 of 347 [98.3%]; week 12: triple pill, 328 of 337 [97.3%]; usual care, 342 of 345 [99.1%]; 6 months: triple pill, 321 of 334 [96.1%]; usual care, 336 of 341 [98.5%]).

Figure 2.. Distribution of Patients by Systolic Blood Pressure (SBP) and Rate of Treatment Intensification

Orange shading indicates patients in the triple pill group and blue shading indicates patients in the usual care group. Lighter shading indicates the patients who underwent treatment intensification during the visit.