A Combination Low-Dose Pill to Control Hypertension?

Remarkable results from a relatively low-cost way to lower moderately high blood pressure

Amid discussions of lower targets for blood pressure (BP), too many people still respond inadequately to antihypertensive medications. One strategy, combining lower doses of several generic, low-cost medications, may be particularly attractive for compliance — and might even reduce risk at modest cost. In an open-label, pragmatic trial, investigators randomized 700 people in Sri Lanka with elevated BP (systolic BP, >140 mm Hg or diastolic BP, >90 mm Hg; patients with diabetes or chronic kidney disease >130 mm Hg systolic or >80 mm Hg diastolic) to a single triple-combination pill using fixed low-dose antihypertensive medications or to usual care (mean age, 56; women, 58%; diabetes, 29%).

Triple therapy involved 20 mg telmisartan, 2.5 mg amlodipine, and 12.5 mg chlorthalidone. Mean baseline BP was 154/90 mm Hg. At 6 months, 33% of the usual-care group were prescribed ≥2 drugs.

The triple-therapy group was more likely than the usual-care group to achieve the 6-month primary outcome, <140/90 mm Hg or <130/80 mm Hg in high-risk patients (69% vs. 55.3%; relative risk, 1.23). The adjusted mean change in systolic BP was –29.1 mm Hg with triple therapy vs. –20.3 mm Hg with usual care. Groups had similar levels of self-reported adherence to medication. Patients in the triple-therapy group had less reduction in LDL cholesterol and were more likely to have hyponatremia and hypokalemia. Rates of serious adverse events, found in 48 patients, were 7.7% and 6.0% in the triple-therapy and usual-care groups, respectively.

Comment:This study, conducted within the Sri Lankan public health system, shows remarkable benefits with a triple-therapy combination pill to control hypertension. The approach is attractive and the result exciting. We should rapidly reproduce the study, validate the finding in other settings, test different combinations, evaluate its impact on patient outcomes — and, if successful, spread its use quickly.

— Harlan M. Krumholz, MD, SM reviewing Webster R et al. JAMA 2018 Aug 14