Telmisartan, amlodipine, and chlorthalidone in a low-dose fixed triple combination – better control of target blood pressure values?

Introduction

Cumulative exposure to high BP is a documented adverse prognostic factor. In diabetology, assessing compensation by the percentage of time spent in the target glycemia range is now a commonly used parameter. Similarly, a parameter for the percentage of time spent in the target BP range and a method for its calculation using extrapolation was created. This calculation method, from routine repeated BP measurements (not continuous monitoring), was developed and published by British experts in 2018. However, until now, studies assessing the impact of antihypertensive treatment on this parameter were lacking. The aim of the secondary analysis of the TRIUMPH study data was therefore to assess whether administering a triple combination of antihypertensives is associated with a higher percentage of time in the target BP range compared to usual care.

Methodology and Course of the TRIUMPH Study

TRIUMPH (Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension) was an open-label randomized clinical study with a low-dose fixed triple combination of antihypertensives conducted in urban hospitals in Sri Lanka in 2016–2017. It included adult patients with moderate hypertension who had a systolic BP > 140 mmHg or a diastolic BP > 90 mmHg; in the case of patients with diabetes or chronic kidney disease, it was sBP > 130 mmHg or dBP > 80 mmHg. These were patients who needed to start or escalate antihypertensive treatment, i.e., those not previously treated for hypertension or treated with only one antihypertensive.

Participants were randomized either to a fixed triple combination containing an AT₁ receptor blocker for angiotensin II, telmisartan at a dose of 20 mg, a calcium channel blocker amlodipine at a dose of 2.5 mg, and a diuretic chlorthalidone at a dose of 12.5 mg in one tablet administered once daily, or to usual care, which is not further specified in the research team's publications. The proportion of time in the target BP range was compared between therapeutic groups over 24 weeks.

Results of the Secondary Analysis

All 700 patients from the TRIUMPH study, with an average age of 56 years, 58% of whom were women, were analyzed. Patients randomized to the fixed triple combination were found to have a significantly higher average percentage of time spent in the target BP range during the 24 weeks of treatment compared to the usual care group (64 vs. 43%; risk difference 21%; 95% confidence interval [CI] 16–26; p < 0.001). Nearly twice as many patients with the fixed triple combination achieved more than half of the time in the target BP range (64 vs. 37%; p < 0.001) compared to those with usual care.

Prolonged time spent in the target BP range was evident very shortly after starting the fixed triple combination therapy. Most patients with the fixed triple combination achieved > 50% time in the target BP range by week 12 of treatment. A higher average proportion of time in the target BP range with the given fixed triple combination of antihypertensives compared to usual care was found in all time intervals assessed: during weeks 0–6 (36.3 vs. 21.7%; p < 0.001), 6–12 (55.2 vs. 33.7%; p < 0.001), and 12–24 (66.0 vs. 43.5%; p < 0.001).

Conclusion

All three medications in the tested fixed combination are substances with a long biological half-life, allowing for the avoidance of significant BP fluctuations throughout the day. The study showed that even in the long-term context, the interplay of the pharmacokinetic properties and pharmacodynamic effects of this antihypertensive triple combination is advantageous. In patients with moderate hypertension, it was associated with a significantly greater proportion of time spent in the target BP range than with usual care.

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Source: Gnanenthiran S. R., Wang N., Di Tanna G. L. et al.; TRIUMPH Study Group. Association of low-dose triple combination therapy vs usual care with time at target blood pressure: a secondary analysis of the TRIUMPH randomized clinical trial. JAMA Cardiol 2022 Jun 1; 7 (6): 645−650, doi: 10.1001/jamacardio.2022.0471.