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Randomized Controlled Trial
. 2022 Jun 1;7(6):645-650.
doi: 10.1001/jamacardio.2022.0471.

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

Sonali R Gnanenthiran  1 , Nelson Wang  1 , Gian Luca Di Tanna  1 , Abdul Salam  2 , Ruth Webster  1   3 , H Asita de Silva  4 , Rama Guggilla  5 , Stephen Jan  1 , Pallab K Maulik  2 , Nitish Naik  6 , Vanessa Selak  7 , Simon Thom  8 , Dorairaj Prabhakaran  9 , Aletta E Schutte  1 , Anushka Patel  1 , Anthony Rodgers  1 ; TRIUMPH Study Group
Collaborators, Affiliations
Randomized Controlled Trial

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

Sonali R Gnanenthiran et al. JAMA Cardiol. .

Erratum in

  • Error in Abstract Results Section.
    [No authors listed] [No authors listed] JAMA Cardiol. 2022 Jun 1;7(6):658. doi: 10.1001/jamacardio.2022.1392. JAMA Cardiol. 2022. PMID: 35674747 Free PMC article. No abstract available.

Abstract

Importance: Cumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking.

Objective: To evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care.

Design, setting, and participants: The Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021.

Intervention: Once-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care.

Main outcomes and measures: Between-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP.

Results: There were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 55.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001).

Conclusions and relevance: To our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Di Tanna was previously an employee of Amgen. Dr Webster reports grants from National Health and Medical Research Council during the conduct of the study. Dr Guggilla is a shareholder of Ajanta Pharma, Asensus Surgical US, Bayer, Cellectis, Cocrystal Pharma, Divi’s Laboratories, Editas Medicine, Intercept Pharmaceuticals, Jaguar Health, Natco Pharma, Roche, and Zynerba Pharmaceuticals. Dr Maulik reports grants from National Health and Medical Research Council and the UK Research and Innovation Medical Research Council outside the submitted work. Dr Schutte reports personal fees from Servier, Novartis, Takeda, Sun Pharmaceuticals, and Abbott outside the submitted work. Dr Patel reports grants from National Health and Medical Research Council during the conduct of the study and is employed by the George Institute for Global Health, which has submitted patent applications in respect of low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease; George Health Enterprises and its subsidiary, George Medicines, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure–lowering drugs; George Health Enterprise is the social enterprise arm of the George Institute for Global Health; Dr Patel does not have a direct financial interest in these patent applications or investments. Dr Rodgers is employed by the George Institute for Global Health and Imperial College London and is seconded part-time to George Medicines, which is partly owned by George Health Enterprises, the social enterprise arm of the George Institute for Global Health; the George Institute for Global Health holds patents for ultra–low-dose fixed-dose combination products for the treatment of hypertension and diabetes, and Dr Rodgers is listed as one of the inventors (US 10,369,15; US 10,799,487; US 10,322,117; US 11,033,544); George Health Enterprises and George Medicines have received funding from public and private investors to conduct the research required for regulatory approval of cardiovascular combination products; Dr Rodgers does not have a financial interest in these patent applications or investments. No other disclosures were reported.

Figures

Figure.
Figure.. Association of Triple Pill Therapy With More than 50% Time at Target Blood Pressure (BP) by Subgroup (N = 700)
See this image and copyright information in PMC

Comment in

References

    1. Williams B, Mancia G, Spiering W, et al. ; ESC Scientific Document Group . 2018 ESC/ESH Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339 - DOI - PubMed
    1. Whelton PK, Carey RM, Aronow WS, et al. . ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2018;71(19):2199-2269. doi:10.1016/j.jacc.2017.11.005 - DOI - PubMed
    1. Chung SC, Pujades-Rodriguez M, Duyx B, et al. . Time spent at blood pressure target and the risk of death and cardiovascular diseases. PLoS One. 2018;13(9):e0202359. doi:10.1371/journal.pone.0202359 - DOI - PMC - PubMed
    1. Liu K, Colangelo LA, Daviglus ML, et al. . Can antihypertensive treatment restore the risk of cardiovascular disease to ideal levels?: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc. 2015;4(9):e002275. doi:10.1161/JAHA.115.002275 - DOI - PMC - PubMed
    1. Tedla YG, Yano Y, Carnethon M, Greenland P. Association between long-term blood pressure variability and 10-year progression in arterial stiffness: the Multiethnic Study of Atherosclerosis. Hypertension. 2017;69(1):118-127. doi:10.1161/HYPERTENSIONAHA.116.08427 - DOI - PMC - PubMed

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