Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension

Overview

Journal Glob Heart

Publisher Ubiquity Press

Specialty Cardiology & Vascular Diseases

Date 2024 Feb 19

PMID 38371656

Authors

Anthony Rodgers

Abdul Salam

William Cushman

Asita de Silva

Gian Luca Di Tanna

Sonali R Gnanenthiran

Diederick Grobbee

Krzysztof Narkiewicz

Dike Ojji

Suzanne Oparil

Neil Poulter

Markus P Schlaich

Aletta E Schutte

Wilko Spiering

Bryan Williams

Jackson T Wright Jr

Paul Whelton

Affiliations

Soon will be listed here.

Abstract

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

References

Salam A, Kanukula R, Atkins E, Wang X, Islam S, Kishore S . Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019; 37(9):1768-1774. DOI: 10.1097/HJH.0000000000002096. View

Salam A, Huffman M, Kanukula R, Hari Prasad E, Sharma A, Heller D . Two-drug fixed-dose combinations of blood pressure-lowering drugs as WHO essential medicines: An overview of efficacy, safety, and cost. J Clin Hypertens (Greenwich). 2020; 22(10):1769-1779. PMC: 8030031. DOI: 10.1111/jch.14009. View

Dzudie A, Rayner B, Ojji D, Schutte A, Twagirumukiza M, Damasceno A . Roadmap to achieve 25% hypertension control in Africa by 2025. Cardiovasc J Afr. 2017; 28(4):262-272. PMC: 5642030. DOI: 10.5830/CVJA-2017-040. View

Campbell N, Schutte A, Varghese C, Ordunez P, Zhang X, Khan T . São Paulo call to action for the prevention and control of high blood pressure: 2020. J Clin Hypertens (Greenwich). 2019; 21(12):1744-1752. PMC: 8030388. DOI: 10.1111/jch.13741. View

Adeloye D, Basquill C . Estimating the prevalence and awareness rates of hypertension in Africa: a systematic analysis. PLoS One. 2014; 9(8):e104300. PMC: 4121276. DOI: 10.1371/journal.pone.0104300. View

Mourad J, Waeber B, Zannad F, Laville M, Duru G, Andrejak M . Comparison of different therapeutic strategies in hypertension: a low-dose combination of perindopril/indapamide versus a sequential monotherapy or a stepped-care approach. J Hypertens. 2004; 22(12):2379-86. DOI: 10.1097/00004872-200412000-00021. View

Chow C, Atkins E, Hillis G, Nelson M, Reid C, Schlaich M . Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. Lancet. 2021; 398(10305):1043-1052. DOI: 10.1016/S0140-6736(21)01922-X. View

Chow C, Teo K, Rangarajan S, Islam S, Gupta R, Avezum A . Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA. 2013; 310(9):959-68. DOI: 10.1001/jama.2013.184182. View

Israili Z . Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens. 2000; 14 Suppl 1:S73-86. DOI: 10.1038/sj.jhh.1000991. View

10.

Mourad J, Amodeo C, De Champvallins M, Brzozowska-Villatte R, Asmar R . Blood pressure-lowering efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled essential hypertension: a multicenter, randomized, double-blind, controlled trial. J Hypertens. 2017; 35(7):1481-1495. DOI: 10.1097/HJH.0000000000001359. View

11.

Thomas J . A review of 10 years of experience with indapamide as an antihypertensive agent. Hypertension. 1985; 7(6 Pt 2):II152-6. DOI: 10.1161/01.hyp.7.6_pt_2.ii152. View

12.

. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021; 397(10285):1625-1636. PMC: 8102467. DOI: 10.1016/S0140-6736(21)00590-0. View

13.

Feldman R, Zou G, Vandervoort M, Wong C, Nelson S, Feagan B . A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial. Hypertension. 2009; 53(4):646-53. DOI: 10.1161/HYPERTENSIONAHA.108.123455. View

14.

Bennett A, Chow C, Chou M, Dehbi H, Webster R, Salam A . Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension. 2017; 70(1):85-93. DOI: 10.1161/HYPERTENSIONAHA.117.09202. View

15.

Liang W, Ma H, Cao L, Yan W, Yang J . Comparison of thiazide-like diuretics versus thiazide-type diuretics: a meta-analysis. J Cell Mol Med. 2017; 21(11):2634-2642. PMC: 5661252. DOI: 10.1111/jcmm.13205. View

16.

Sica D . Calcium channel blocker class heterogeneity: select aspects of pharmacokinetics and pharmacodynamics. J Clin Hypertens (Greenwich). 2005; 7(4 Suppl 1):21-6. PMC: 8109523. DOI: 10.1111/j.1524-6175.2006.04482.x. View

17.

Benjamin I, Kreutz R, Olsen M, Schutte A, Lopez-Jaramillo P, Frieden T . Fixed-dose combination antihypertensive medications. Lancet. 2019; 394(10199):637-638. DOI: 10.1016/S0140-6736(19)31629-0. View

18.

Olde Engberink R, Frenkel W, van den Bogaard B, Brewster L, Vogt L, van den Born B . Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis. Hypertension. 2015; 65(5):1033-40. DOI: 10.1161/HYPERTENSIONAHA.114.05122. View

19.

Anderson C, Rodgers A, de Silva H, Martins S, Klijn C, Senanayake B . Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress. Int J Stroke. 2022; 17(10):1156-1162. DOI: 10.1177/17474930211068671. View

20.

Wald D, Law M, Morris J, Bestwick J, Wald N . Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009; 122(3):290-300. DOI: 10.1016/j.amjmed.2008.09.038. View