Triple Drug Hypertension Pill Reduces Blood Pressure to Target Levels

Ruth Webster, PhD

A study of patients with mild to moderate hypertension found that a low-dose triple combination of antihypertensive medications successfully reduced hypertension to target blood pressure in 70% of patients compared to 55% of patients in the standard care group.

The pragmatic randomized clinical trial—Triple Pill vs Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) study—tested a triple combination pill containing 20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone.

“In low- and middle-income settings, the availability and affordability of medications is a critical issue, and only about one-third of individuals with high blood pressure in these settings receive treatment,” wrote study authors Ruth Webster, PhD, and Abdul Salam, PhD, of The George Institute for Global Health, University of New South Wales; and H. Asita de Silva, DPhil, of University of Kelaniya, Ragama, Sri Lanka; et al.

However, the authors note that even in high-income countries, only about half of patients treated for hypertension achieve their target blood pressure (BP) levels. They added that in most settings, inadequate blood pressure control is due to “persistent use of monotherapy, which has modest efficacy.”

The study included 700 patients with a mean age of 56 years and mild to moderate hypertension; 58% were women, and 29% had diabetes. The research was conducted in 11 urban hospital outpatient departments across Sri Lanka, which is classified as a middle-income country.

The target blood pressure was defined as a systolic blood pressure of less than 140 mm HG and a diastolic BP of lower than 90 mm Hg.

At the final, 6-month visit, 69.5% of patients receiving the triple combination pill reached the target blood pressure compared with 55.3% in the usual care group (adjusted RR, 1.23 [95% CI, 1.09-1.39], P&thinsp;<&thinsp;.001; risk difference, 12.7% [95% CI, 3.2%-22.0%]).

Additionally, 67.8% of patients in the triple combination treatment group achieved blood pressure target levels at 6 weeks, compared to 43.6% of the usual care group (RR, 1.53 [95% CI, 1.33-1.76], P&thinsp;<&thinsp;.001; risk difference, 23.2% [95% CI, 14.7%-31.0%]). At 12 weeks, those numbers were 72.6% and 47.4%, respectively (RR, 1.51 [95% CI, 1.32-1.72], P&thinsp;<&thinsp;.001; risk difference, 24.3% [95% CI, 16.1%-31.8%]).

There were 419 adverse events, with 38.1% of participants in the triple combination group and 34.8% in the standard care group reporting at least 1 adverse event. The most common adverse events were musculoskeletal pain (6% in the combination pill group vs 8% in the usual care group), dizziness, presyncope, or syncope (5.2% vs 2.8%, respectively), and headache (3.7% vs 3.1%).

“Even though larger trials are needed to evaluate longer-term safety in more diverse populations, the initial safety signal appears promising,” wrote Mark D. Huffman, MD, MPH; Gbenga Ogedegbe, MD, MPH; and Marc Jaffe, MD, in a commentary on the TRIUMPH study.

While the study was conducted in a middle-income country with a public health care system that provides medications like the studied hypertensive drugs free of charge, the results have implications for clinical practice in the United States and other high-income countries as well.

“The results also may have relevance to high-income countries that have lower control rates for hypertension than the rates seen in this trial despite considerable health service investments,” noted Webster, Salam, and de Silva, et al. “The results are also particularly important in light of recent recommendations for lower blood pressure targets in high-risk individuals.”

These recent hypertension guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) redefined hypertension as blood pressure above the normal level of 120/80 mm Hg.

A study of these hypertension guidelines found that fulfillment of the standards would reduce major cardiovascular events including nonfatal strokes, nonfatal myocardial infarction, and cardiovascular deaths, by 23% annually in US adults ≥40 years.

Given the widespread prevalence of hypertension and the challenges to achieving blood pressure control in many patients, findings of the TRIUMPH study are especially promising.

“The TRIUMPH investigators have demonstrated the effects of a promising intervention in a triple half-dose combination therapy, which logically extends findings from prior research to improve BP control among patients with mild to moderate hypertension,” wrote Huffman, Ogedegbe, and Jaffe. “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.”

The study, “Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri Lanka” was published in JAMA on August 14, 2018.