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A triple combination antihypertensive pill was associated with improved blood pressure (BP) control despite more therapeutic inertia, according to a secondary analysis of the TRIUMPH trial.

People who didn't achieve their BP goal on the polypill -- containing low doses of an angiotensin receptor blocker, a diuretic, and a calcium channel blocker -- were nevertheless more likely than controls receiving usual care to forgo treatment intensification at 6 weeks (86.8% vs 63.9%, P<0.001) and 12 weeks (90% vs 64.8%, P<0.001).

However, the polypill group had more patients reach BP targets (69.5% vs 55.3% by month 6, P<0.001), reported Anthony Rodgers, PhD, of the George Institute for Global Health and the University of New South Wales in Sydney, and colleagues, in their study .

"Thus, even if use of FDC [fixed-dose combination] pills increased therapeutic inertia, the negative outcome was offset by the substantial upfront advantage in BP control," noted an by Ann Marie Navar, MD, PhD, of Duke Clinical Research Institute in Durham, North Carolina, and Thomas Wang, MD, of the University of Texas Southwestern Medical Center in Dallas.

The increase in therapeutic inertia could be explained in part by the lower systolic BP at 6 and 12 weeks among those who did not reach BP targets on the polypill, Rodgers' group reported.

"In other words, participants in the usual care arm might have been more likely to have their medications increased because they were further away from their BP targets than their counterparts in the FDC arm," according to Navar and Wang.

"Had uptitration occurred in the FDC arm at the same rate as it did in the usual care arm, the advantage in BP control in the FDC group compared with usual care may have been even greater at the end of the trial," the editorialists wrote.

Multiple randomized trials have shown the safety and effectiveness of polypills in hypertension management, Navar and Wang noted. "Future guidelines should consider allowing clinicians to consider an FDC-first approach for a broader population of patients than is currently recommended."

The study included the original 700 participants with persistent mild-to-moderate hypertension (57.6% women, mean age 56 years) who were enrolled from 11 urban hospital clinics in Sri Lanka in 2016-2017.

Randomization divided the cohort between the polypill arm -- taking a once-daily pill containing 20-mg telmisartan, 2.5-mg amlodipine, and 12.5-mg chlorthalidone -- and a usual-care arm.

Combination therapy could be taken in tandem with other BP-lowering drugs. Polypill patients were also allowed to get a higher-dose version (40-mg telmisartan, 5-mg amlodipine, and 25-mg chlorthalidone) at the physician's discretion.

This uptitration only occurred in 2.9% of patients, signaling the clinicians' reluctance to adopt the higher-dose pill, Rodgers and colleagues said. Nearly all patients assigned to FDC therapy had already received BP treatment intensification at randomization by virtue of the study's design.

TRIUMPH's BP target was <140/90 mm Hg (or <130/80 mm Hg for those with diabetes or chronic kidney disease).

The polypill simplified treatment for many patients in the trial, as there was reduction in the number of clinical pathways comparing the polypill group with controls (23 vs 54 per 100 treated patients, P<0.001). The most common pathway for both groups was intensification of therapy at baseline, followed by sustained achievement in BP target at each subsequent follow-up visit.

"By specifying the timing of patient visits, the study did not fully reflect real-world treatment of hypertension," investigators acknowledged.

Further analysis of the TRIUMPH trial will investigate prescriber-related reasons for therapeutic inertia, they noted.

Strategies to prevent such inertia "may include education, incentives for appropriate treatment intensification, and physician feedback or reminders," Rodgers' team suggested.

Another option is "to provide multiple dosing options, so that clinicians can have greater prescribing flexibility without losing the simplicity of a combination pill," according to the editorialists.

"Implementation of FDC into clinical practice should be part of longitudinal care pathways, with reassessment of BP over time and algorithms to uptitrate therapy for those whose BP remain greater than the goal value. Similar considerations apply to assessment of lipids if the use of polypills containing both antihypertensive medications and statins becomes widespread," they said.

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