Low-dose 3-in-1 polypill TRIUMPHs over usual care in BP control

Pearl Toh
19 Mar 2018
Ruth Webster
Dr Ruth Webster

A polypill containing fixed low doses of three antihypertensive drugs led to better blood pressure (BP) control without increased adverse effects compared with usual care among people with persistent hypertension, according to the TRIUMPH* trial.

At 6 months, significantly more patients taking the triple drug combination pill containing telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg were able to achieve their BP targets compared with those on usual care (69.5 percent vs 55.3 percent, relative risk [RR], 1.23; p=0.0007). [ACC.18, abstract 408-14]

The maximum difference between the two arms was seen at as early as 6 weeks (67.8 percent vs 43.6 percent, RR, 1.53; p<0.001), which reflects a 53 percent reduction in risk for high BP with the polypill.

“The benefits were seen straight away and maintained until 6 months,” said lead author Dr Ruth Webster of The George Institute for Global Health at the University of New South Wales in Sydney, Australia. The mean BP reduction at 6 months was 8.8 and 4.6 mm Hg for systolic and diastolic BP, respectively with the polypill relative to usual care (p<0.001 for both).

The open-label trial involved 700 individuals (mean age 56 years, 58 percent women) with persistent hypertension (mean BP 154/90 mm Hg) who were untreated and requiring therapy initiation or who were on monotherapy requiring up-titration. They were randomized 1:1 to receive the fixed-dose triple drug combination pill or usual care based on physician’s choice of antihypertensive medication. BP control was defined as achieving target levels of <140/90 mm Hg, or <130/80 mm Hg for those with diabetes and/or chronic kidney disease.

Rates of adverse events were comparable between the two arms (38.1 percent vs 34.5 percent; p=0.51). The rates of therapy withdrawal due to adverse events were also similar (6.6 percent vs 6.8 percent; p=0.92).

“Early use of a low dose 3-in-1 combination BP-lowering pill … provides faster, better control of BP compared to usual care … and just as safe as current approaches,” said Webster.

Potential benefits of triple combo

Currently, many patients are still not reaching their target BP globally and require up-titration to more than one antihypertensive drug to achieve the target, observed Webster. However, up-titration increases the complexity of treatment, adding difficulty for patients to adhere to a multipill regimen.

“We don’t necessarily need a new blockbuster drug. We need novel ways of using what we already have,” said Webster.

She believed that combining these drugs in a single pill would facilitate physician “inertia” to up-titration and enhance patient adherence.   

“There are potential advantages of using low-dose combination therapy. We get additive benefits among the multiple drug classes, [and] the low dose minimizes adverse effects ... Compared to the standard full dose, about 80 percent of the effectiveness of BP-lowering drugs is achieved at half dose.”  

Although adherence did not improve significantly with the polypill vs the usual care arms in the study, Webster suggested that it might be because the number of pills that people were taking was comparable between the two arms to begin with, and that the method of measuring adherence was not entirely reliable.

“[This study] strongly supports the strategy of early use of low-dose triple combination therapy in all settings,” Webster concluded, noting that the benefits with the polypill were seen regardless of age, sex, diabetes comorbidity, or baseline BP in prespecified subgroup analysis. “The most urgent need is effective implementation and scale up in low and middle-income countries with greatest disease burden.”

Low-dose 3-in-1 polypill triumphs over usual care in BP control
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