Comparison of three dual therapies for lowering blood pressure: a multi-country randomized clinical trial

Abstract

OBJECTIVE: Hypertension guidelines currently recommend initiating treatment with low-dose dual single pill combinations (SPCs) of blood pressure (BP) medications for most patients. However, randomized double-blind comparisons between dual SPCs are limited. As part of an evaluation of a low-dose triple SPC, we compared three dual SPCs, each containing two of telmisartan (T), amlodipine (A) or indapamide (I). DESIGN AND METHOD: This randomized, double-blind trial enrolled adults with hypertension receiving 0-3 BP medications from Australia, Czech Republic, New Zealand, Poland, Sri Lanka, United Kingdom and the USA. After a 4-week run-in switching existing BP medications to a triple SPC at T20 mg/A2.5 mg/I1.25 mg, participants were randomised to one of three dual SPCs (T20 mg/A2.5 mg, T20 mg/I1.25 mg, or A2.5 mg/I1.25 mg). After 6 weeks the doses were doubled, unless contraindicated. The primary efficacy outcome was change in home SBP from randomisation to week 12. The primary safety outcome was withdrawal of treatment due to adverse events. The trial was completed on 1 September 2023. RESULTS: Before run-in, participants (n=834) were on average on 1.6 BP medications and mean clinic BP was 142/85 mmHg. Following the active run-in mean home BP was 129/78 mmHg. 834 participants were randomised (mean age 59 years, 52% female). At week 12, mean home SBP of the TI, TA and AI groups were: 131 (95% CI: 130, 132), 134 (133, 135), and 133 (132, 134) mmHg, respectively, with TI superior to TA (3.1, 1.8-4.4, p<0.0001) and AI (2.1, 0.7-3.4, p=0.0027). Home BP control (<135/85 mmHg) at week 12 was 64%, 58% and 56% in the TI, TA and AI groups. Withdrawal of treatment due to adverse events occurred in 1.5%, 1.1% and 1.4%; symptomatic hypotension occurred in 4.0%, 1.8%, and 1.4% of TI, TA and AI groups (all comparisons at p>0.05). CONCLUSIONS: In this randomized, double-blind comparison of three dual SPCs, TI showed a greater home SBP lowering efficacy compared to TA or AI, with similar tolerability for all three SPCs. Although dual combinations of major drug classes are equally recommended in hypertension guidelines, these findings suggest superior efficacy of TI compared to TA and AI at these doses.