Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes

Yoichiro Hirakawa, Hisatomi Arima, Ruth Webster, Sophia Zoungas, Qiang Li, Stephen Harrap, Liu Lisheng, Pavel Hamet, Giuseppe Mancia, Neil Poulter, Bruce Neal, Bryan Williams, Anthony Rogers, Mark Woodward, John Chalmers

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: The associations of discontinuation of the study medication on major outcomes were assessed in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Trial. Methods: ADVANCE was a factorial randomized controlled trial of blood pressure lowering (a fixed combination of perindopril and indapamide vs. placebo) and intensive glucose control (vs. standard glucose control) in patients with type 2 diabetes. Patients who permanently discontinued the randomized blood pressure-lowering medication during the study period (n=1557) were compared with others (n=9583). Cox's proportional hazards models were used to estimate the effects of the discontinuation on the risks of macrovascular events, microvascular events together and separately and all-cause mortality, using discontinuation as a time-dependent covariate. Results: In multivariable analyses, discontinuation was associated with increased risks of combined macro and microvascular events (hazard ratio 2.24, 95% CI 1.96-2.57), macrovascular events (3.23, 2.75-3.79), microvascular events (1.38, 1.11-1.71), and all-cause mortality (7.99, 6.92-9.21) compared to continuing administration of randomized medications during the trial period, which were highest in the first year after discontinuation. These associations were similar in active and placebo groups, except in the first year after discontinuation during which event rates were lower in the active group than in the placebo group (P≤0.01). Conclusion: Discontinuation of study medication is a potent risk marker for identifying high-risk patients. Thus it is important that clinicians seek to identify such patients early after discontinuation of treatment. Although some short-term residual effects of previous active treatment can be expected, patients who discontinue require further urgent investigation and management.

Original languageEnglish
Pages (from-to)781-787
Number of pages7
JournalJournal of hypertension
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Type 2 Diabetes Mellitus
Blood Pressure
perindopril drug combination indapamide
Placebos
Indapamide
Gliclazide
Perindopril
Glucose
Mortality
Vascular Diseases
Proportional Hazards Models
Randomized Controlled Trials
Therapeutics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes. / Hirakawa, Yoichiro; Arima, Hisatomi; Webster, Ruth; Zoungas, Sophia; Li, Qiang; Harrap, Stephen; Lisheng, Liu; Hamet, Pavel; Mancia, Giuseppe; Poulter, Neil; Neal, Bruce; Williams, Bryan; Rogers, Anthony; Woodward, Mark; Chalmers, John.

In: Journal of hypertension, Vol. 34, No. 4, 01.04.2016, p. 781-787.

Research output: Contribution to journalArticle

Hirakawa, Y, Arima, H, Webster, R, Zoungas, S, Li, Q, Harrap, S, Lisheng, L, Hamet, P, Mancia, G, Poulter, N, Neal, B, Williams, B, Rogers, A, Woodward, M & Chalmers, J 2016, 'Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes', Journal of hypertension, vol. 34, no. 4, pp. 781-787. https://doi.org/10.1097/HJH.0000000000000841
Hirakawa, Yoichiro ; Arima, Hisatomi ; Webster, Ruth ; Zoungas, Sophia ; Li, Qiang ; Harrap, Stephen ; Lisheng, Liu ; Hamet, Pavel ; Mancia, Giuseppe ; Poulter, Neil ; Neal, Bruce ; Williams, Bryan ; Rogers, Anthony ; Woodward, Mark ; Chalmers, John. / Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes. In: Journal of hypertension. 2016 ; Vol. 34, No. 4. pp. 781-787.
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abstract = "Objective: The associations of discontinuation of the study medication on major outcomes were assessed in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Trial. Methods: ADVANCE was a factorial randomized controlled trial of blood pressure lowering (a fixed combination of perindopril and indapamide vs. placebo) and intensive glucose control (vs. standard glucose control) in patients with type 2 diabetes. Patients who permanently discontinued the randomized blood pressure-lowering medication during the study period (n=1557) were compared with others (n=9583). Cox's proportional hazards models were used to estimate the effects of the discontinuation on the risks of macrovascular events, microvascular events together and separately and all-cause mortality, using discontinuation as a time-dependent covariate. Results: In multivariable analyses, discontinuation was associated with increased risks of combined macro and microvascular events (hazard ratio 2.24, 95{\%} CI 1.96-2.57), macrovascular events (3.23, 2.75-3.79), microvascular events (1.38, 1.11-1.71), and all-cause mortality (7.99, 6.92-9.21) compared to continuing administration of randomized medications during the trial period, which were highest in the first year after discontinuation. These associations were similar in active and placebo groups, except in the first year after discontinuation during which event rates were lower in the active group than in the placebo group (P≤0.01). Conclusion: Discontinuation of study medication is a potent risk marker for identifying high-risk patients. Thus it is important that clinicians seek to identify such patients early after discontinuation of treatment. Although some short-term residual effects of previous active treatment can be expected, patients who discontinue require further urgent investigation and management.",
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AU - Hirakawa, Yoichiro

AU - Arima, Hisatomi

AU - Webster, Ruth

AU - Zoungas, Sophia

AU - Li, Qiang

AU - Harrap, Stephen

AU - Lisheng, Liu

AU - Hamet, Pavel

AU - Mancia, Giuseppe

AU - Poulter, Neil

AU - Neal, Bruce

AU - Williams, Bryan

AU - Rogers, Anthony

AU - Woodward, Mark

AU - Chalmers, John

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N2 - Objective: The associations of discontinuation of the study medication on major outcomes were assessed in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Trial. Methods: ADVANCE was a factorial randomized controlled trial of blood pressure lowering (a fixed combination of perindopril and indapamide vs. placebo) and intensive glucose control (vs. standard glucose control) in patients with type 2 diabetes. Patients who permanently discontinued the randomized blood pressure-lowering medication during the study period (n=1557) were compared with others (n=9583). Cox's proportional hazards models were used to estimate the effects of the discontinuation on the risks of macrovascular events, microvascular events together and separately and all-cause mortality, using discontinuation as a time-dependent covariate. Results: In multivariable analyses, discontinuation was associated with increased risks of combined macro and microvascular events (hazard ratio 2.24, 95% CI 1.96-2.57), macrovascular events (3.23, 2.75-3.79), microvascular events (1.38, 1.11-1.71), and all-cause mortality (7.99, 6.92-9.21) compared to continuing administration of randomized medications during the trial period, which were highest in the first year after discontinuation. These associations were similar in active and placebo groups, except in the first year after discontinuation during which event rates were lower in the active group than in the placebo group (P≤0.01). Conclusion: Discontinuation of study medication is a potent risk marker for identifying high-risk patients. Thus it is important that clinicians seek to identify such patients early after discontinuation of treatment. Although some short-term residual effects of previous active treatment can be expected, patients who discontinue require further urgent investigation and management.

AB - Objective: The associations of discontinuation of the study medication on major outcomes were assessed in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Trial. Methods: ADVANCE was a factorial randomized controlled trial of blood pressure lowering (a fixed combination of perindopril and indapamide vs. placebo) and intensive glucose control (vs. standard glucose control) in patients with type 2 diabetes. Patients who permanently discontinued the randomized blood pressure-lowering medication during the study period (n=1557) were compared with others (n=9583). Cox's proportional hazards models were used to estimate the effects of the discontinuation on the risks of macrovascular events, microvascular events together and separately and all-cause mortality, using discontinuation as a time-dependent covariate. Results: In multivariable analyses, discontinuation was associated with increased risks of combined macro and microvascular events (hazard ratio 2.24, 95% CI 1.96-2.57), macrovascular events (3.23, 2.75-3.79), microvascular events (1.38, 1.11-1.71), and all-cause mortality (7.99, 6.92-9.21) compared to continuing administration of randomized medications during the trial period, which were highest in the first year after discontinuation. These associations were similar in active and placebo groups, except in the first year after discontinuation during which event rates were lower in the active group than in the placebo group (P≤0.01). Conclusion: Discontinuation of study medication is a potent risk marker for identifying high-risk patients. Thus it is important that clinicians seek to identify such patients early after discontinuation of treatment. Although some short-term residual effects of previous active treatment can be expected, patients who discontinue require further urgent investigation and management.

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