Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials.

Salam, A; Atkins, ER; Hsu, B; Webster, R; Patel, A; Rodgers, A

Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials.

Salam, A Atkins, ER Hsu, B Webster, R

Patel, A Rodgers, A

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Publication Type:: Journal Article
Citation:: Journal of hypertension, 2019, 37, (8), pp. 1567-1573
Issue Date:: 2019-05

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Field	Value	Language
dc.contributor.author	Salam, A
dc.contributor.author	Atkins, ER
dc.contributor.author	Hsu, B
dc.contributor.author	Webster, R https://orcid.org/0000-0002-7444-3037
dc.contributor.author	Patel, A
dc.contributor.author	Rodgers, A
dc.date.accessioned	2020-05-01T01:33:50Z
dc.date.available	2020-05-31T19:25:30Z
dc.date.issued	2019-05
dc.identifier.citation	Journal of hypertension, 2019, 37, (8), pp. 1567-1573
dc.identifier.issn	0263-6352
dc.identifier.issn	1473-5598
dc.identifier.uri	http://hdl.handle.net/10453/140379
dc.description.abstract	BACKGROUND AND OBJECTIVES:Most patients with hypertension need at least two drugs to achieve goal blood pressure. This systematic review assessed efficacy and safety of triple versus dual combination therapy for the management of hypertension. METHODS:Publication databases, clinical trial registries and regulatory agency websites were searched until April 2018 for double-blind randomized controlled trials (RCTs) comparing triple with dual therapy of BP-lowering drugs, for at least 3 weeks, among patients with hypertension. Meta-analyses for efficacy and safety outcomes were performed using random-effects model. Regimen efficacy was predicted using the Therapeutic Intensity Score (TIS) and the Law et al. method (which predict dose doubling increases efficacy by 100% and around 20%, respectively), and compared with observed efficacy. RESULTS:Fourteen RCTs (11 457 participants) were included. Overall, triple compared with dual therapy reduced BP by 5.4/3.2 mmHg (P < 0.001), and improved BP control by 58 versus 45% [relative risk (RR) 1.33 (95% CI 1.25-1.41)], whereas incidence of withdrawals because of adverse events were 3.3 versus 3.4% [RR 1.24 (95% CI 1.00-1.54), P = 0.05]. Law et al.'s method was superior to TIS in predicting differences in efficacy between triple and dual therapies. For patients uncontrolled on submaximal dose dual therapy, adding a third drug achieved on average approximately four times more BP reduction than doubling the dose of dual therapy component drugs (6.0/3.6 versus 1.5/0.8 mmHg, respectively). CONCLUSION:Addition of a third drug is likely to be more efficacious without increasing adverse events, compared with increasing dose of existing dual therapy. Early use of triple therapy can significantly improve hypertension control.
dc.format	Print-Electronic
dc.language	eng
dc.relation.ispartof	Journal of hypertension
dc.relation.isbasedon	10.1097/hjh.0000000000002089
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1116 Medical Physiology
dc.subject.classification	Cardiovascular System & Hematology
dc.title	Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials.
dc.type	Journal Article
utslib.citation.volume	37
utslib.location.activity	England
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1103 Clinical Sciences
utslib.for	1116 Medical Physiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Business
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-05-01T01:33:48Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	37
utslib.start-page	1567
utslib.citation.issue	8

Abstract:

BACKGROUND AND OBJECTIVES:Most patients with hypertension need at least two drugs to achieve goal blood pressure. This systematic review assessed efficacy and safety of triple versus dual combination therapy for the management of hypertension. METHODS:Publication databases, clinical trial registries and regulatory agency websites were searched until April 2018 for double-blind randomized controlled trials (RCTs) comparing triple with dual therapy of BP-lowering drugs, for at least 3 weeks, among patients with hypertension. Meta-analyses for efficacy and safety outcomes were performed using random-effects model. Regimen efficacy was predicted using the Therapeutic Intensity Score (TIS) and the Law et al. method (which predict dose doubling increases efficacy by 100% and around 20%, respectively), and compared with observed efficacy. RESULTS:Fourteen RCTs (11 457 participants) were included. Overall, triple compared with dual therapy reduced BP by 5.4/3.2 mmHg (P < 0.001), and improved BP control by 58 versus 45% [relative risk (RR) 1.33 (95% CI 1.25-1.41)], whereas incidence of withdrawals because of adverse events were 3.3 versus 3.4% [RR 1.24 (95% CI 1.00-1.54), P = 0.05]. Law et al.'s method was superior to TIS in predicting differences in efficacy between triple and dual therapies. For patients uncontrolled on submaximal dose dual therapy, adding a third drug achieved on average approximately four times more BP reduction than doubling the dose of dual therapy component drugs (6.0/3.6 versus 1.5/0.8 mmHg, respectively). CONCLUSION:Addition of a third drug is likely to be more efficacious without increasing adverse events, compared with increasing dose of existing dual therapy. Early use of triple therapy can significantly improve hypertension control.

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