Hot Line: Could a low-dose triple single-pill combination help overcome therapeutic inertia in hypertension management?
01 Sep 2024
Yesterday, Professor Anthony Rodgers (The George Institute for Global Health - Sydney, Australia) described 2 international double-blind trials investigating the effects of GMRx2, a low-dose triple single-pill combination (SPC), that contains telmisartan, amlodipine and indapamide.
A placebo-controlled trial investigated GMRx2 at quarter doses (10 mg, 1.25 mg and 0.625 mg) and half doses (20 mg, 2.5 mg and 1.25 mg) in adults with hypertension receiving 0–1 BP-lowering drugs. After a 2-week placebo run-in, 295 patients with home systolic BP 130–154 mmHg were eligible for randomisation (2:2:1) to GMRx2 quarter dose, GMRx2 half dose or placebo.
At week 4, the placebo-corrected difference in home SBP was −7.3 mmHg (95% CI −4.5 to −10.8) with the GMRx2 quarter dose and −8.2 mmHg (−5.2 to −11.3) with the GMRx2 half dose. Clinic BP control (<140/90 mmHg) was achieved in 37% of participants with placebo, and by 65% and 70% of participants in the GMRx2 quarter- and half-dose groups, respectively (both p<0.001 vs. placebo). Withdrawal of treatment due to adverse events (AEs) occurred in 1.6% of participants with placebo and 0% and 5.1% with GMRx2 quarter- and half-dose groups, respectively.
An active-controlled trial enrolled adults with hypertension receiving 0–3 BP-lowering drugs with screening SBP of 140–179 mmHg (on 0 drugs) to 110–150 mmHg (on 3 drugs). In a 4-week active run-in, existing medications were switched to GMRx2 half dose. In total, 1,385 participants were randomised (2:1:1:1) to continued GMRx2 half dose or each possible dual combination of components at half doses. At week 6, doses were doubled in all groups, unless there was a contraindication.
At week 12, home BP was lower with GMRx2 than with telmisartan-indapamide, telmisartan-amlodipine and amlodipine-indapamide (with reductions of 2.5/2.1, 5.4/3.4 and 4.4/3.6 mmHg, respectively; all p<0.0001 vs. GMRx2). The proportion of participants with clinic BP <140/90 mmHg was 74% with GMRx2, 61% with telmisartan-indapamide, 61% with telmisartan-amlodipine and 53% with amlodipine-indapamide (p≤0.0001 vs. GMRx2). Withdrawal of treatment due to AEs occurred in 2.0% of the GMRx2 participants and 1.4%, 1.1% and 1.4% of telmisartan-indapamide, telmisartan-amlodipine and amlodipine-indapamide groups, respectively.
“GMRx2 reduced BP quickly in mild-to-moderate hypertension and more effectively than dual therapy in a broad, large hypertensive population, without safety concerns. The availability of an SPC could help to reduce current therapeutic inertia, helping patients achieve BP control quickly in a small number of steps, with potential benefits for improved adherence,” concluded Prof. Rodgers.
Professor Dike Ojji (University of Abuja - Abuja, Nigeria) then described the VERONICA-Nigeria trial with GMRx2. This open-label trial was conducted at 3 hospital-based family medicine clinics in Nigeria and involved 300 Black African adults with uncontrolled hypertension (office SBP 140–179 mmHg and/or DBP 90–109 mmHg) who were untreated (treatment naïve or currently untreated) or uncontrolled on monotherapy. Participants were randomised to receive GMRx2 or standard care. The GMRx2 group received once-daily one-quarter, one-half or standard doses, which were up titrated sequentially, aiming to achieve BP <135/85 mmHg. The standard-care group were treated based on the Nigeria hypertension treatment protocol for primary care,1 which involves monthly steps (amlodipine, losartan and hydrochlorothiazide added sequentially) to achieve BP <140/90 mmHg.
At 6 months, mean home SBP reduced by 31 mmHg in the GMRx2 group and by 26 mmHg in the standard-care group (adjusted difference −5.8 mmHg; 95% CI −3.6 to −8.0; p<0.001). Clinic BP control (<140/90 mmHg) was better in the GMRx2 group (82%) than in the standard-care group (82% vs. 72%). No participants discontinued trial treatment due to AEs.
“Although hypertension is a primary driver of the increasing CVD burden in sub-Saharan Africa, only a very small fraction of people receive treatment and those who are treated rarely achieve BP control. We found that the effects of GMRx2 in Nigerian patients appeared consistent with those seen in broader populations, demonstrating excellent effectiveness, even when compared against a standard-care protocol that achieved much better results than usually seen in routine practice,” concluded Prof. Ojji.
References
- Nigeria Hypertension Treatment Protocol for Primary Health Care level. Available at: https://resolvetosavelives.org/wp-content/uploads/2023/05/nigeria-hypertension-protocol-04-1.pdf
