Patients who were prescribed a single pill with low doses of three antihypertensive medications reached their blood pressure (BP) targets more often than those following a usual care plan, according to a randomized trial of 700 individuals from the Sri Lankan public health system.
Study participants had mild to moderate hypertension, defined as diastolic blood pressure between 90 and 110 mm Hg and systolic blood pressure between 140 and 180 mm Hg—or BP above 130/80 for people with diabetes or chronic kidney disease. They were all taking either no antihypertensive therapy or only one such medication before enrollment in the open-label trial.
However, within six months, 70 percent of the patients receiving the fixed-dose combination therapy achieved BP below those targets (140/90 or 130/80 for diabetes or chronic kidney disease). Fifty-five percent of the patients in the usual care group met those targets.
Overall, patients taking the combination pill achieved systolic BPs an average of 9.8 mm Hg lower than the usual care group, and diastolic BPs an average of 5 mm Hg lower.
“The clinical and research implications of these findings principally relate to the need for replication and for a global increase in treatment,” wrote lead author Ruth Webster, PhD, with the University of South Wales in Sydney, Australia, and colleagues. They published their results online Aug. 14 in JAMA after presenting preliminary findings at the American College of Cardiology's annual scientific sessions in March.
“The scale of blood pressure-attributable disease burden and the scarcity of health resources in low- and middle-income countries warrant urgent adoption of more effective and cost-effective blood pressure-control strategies.”
Monotherapy is often inadequate for blood pressure control, the authors noted, and prescribing several different pills increases treatment complexity and nonadherence. But a single pill that offers doses of multiple antihypertensive agents could be an effective, low-cost treatment regimen that patients are more likely to follow.
In this study, the combination pill contained 20 mg of telmisartan, 2.5 mg of amlodipine and 12.5 mg of chlorthalidone—half of the standard dose of each drug. Adverse events were reported in 38.1 percent of the triple therapy group and 34.8 percent for the usual care patients, mostly related to musculoskeletal pain and dizziness or syncope.
“This study contributes to the existing literature demonstrating the essential role of fixed-dose combination therapy as a viable strategy for BP control on a global scale,” wrote Mark D. Huffman, MD, MPH; Gbenga Ogedegbe, MD, MPH; and Marc Jaffe, MD, in a related editorial.
Physicians had the option to further titrate medication during follow-up, but the authors found 65 percent of patients in the usual care group were still prescribed monotherapy at six months and only 3 percent of patients prescribed the fixed-dose pills advanced to receive full doses of each of the three agents.
“The main reasons for not intensifying treatment are (1) an assumption that a patient’s existing treatment has not yet achieved the full effect or (2) clinician satisfaction with a patient’s blood pressure that has decreased or is near goal,” Webster et al. wrote. “Such therapeutic inertia is a major factor in the failure to reach blood pressure goals globally, and was observed in patients within both groups in this pragmatic trial.”
The authors noted drugs were dispensed more frequently to patients in the usual care group, which could have given them more opportunities for treatment titration. In addition, the medications for both cohorts were provided free of charge, which is typical in Sri Lankan public health systems but may not be generalizable to other settings.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.