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Blood pressure changes following antihypertensive medication reduction by drug class and dose chosen for withdrawal: exploratory analysis of data from the optimise trial

Blood pressure changes following antihypertensive medication reduction by drug class and dose chosen for withdrawal: exploratory analysis of data from the optimise trial
Blood pressure changes following antihypertensive medication reduction by drug class and dose chosen for withdrawal: exploratory analysis of data from the optimise trial
Aims: deprescribing of antihypertensive drugs is recommended for some older patients with polypharmacy, but there is little evidence to inform which drug (or dose) should be withdrawn. This study used data from the OPTiMISE trial to examine whether short-term outcomes of deprescribing vary by drug class and dose of medication withdrawn. 

Methods: the OPTiMISE trial included patients aged ≥80 years with controlled systolic blood pressure (SBP; <150 mmHg), receiving ≥2 antihypertensive medications. This study compared SBP control, mean change in SBP and frequency of adverse events after 12-weeks in participants stopping one medication vs. usual care, by drug class and equivalent dose of medication withdrawn. Equivalent dose was determined according to the defined daily dose (DDD) of each medication type. Drugs prescribed below the DDD were classed as low dose and those prescribed at ≥DDD were described as higher dose. Outcomes were examined by generalised linear mixed effects models. 

Results: a total of 569 participants were randomised, aged 85±3 years with controlled blood pressure (mean 130/69mmHg). Within patients prescribed calcium channel blockers, higher dose medications were more commonly selected for withdrawal (90% vs. 10%). In those prescribed beta-blockers, low dose medications were more commonly chosen (87% vs. 13%). Withdrawal of calcium channel blockers was associated with an increase in SBP (5mmHg, 47 95%CI 0 to 10 mmHg) and reduced SBP control (adjusted RR 0.89, 95%CI 0.80 to 0.998) compared to usual care. In contrast, withdrawal of beta-blockers was associated with no change in SBP (-4mmHg, 95%CI -10 to 2mmHg) and no difference in SBP control (adjusted RR 1.15, 95%CI 0.96 to 1.37). Similarly, withdrawal of higher dose medications was associated with an increase in SBP but no change in BP control. Withdrawal of lower dose medications was not associated with a difference in SBP or SBP control. There was no association between withdrawal of specific drug classes and adverse events. 

Conclusions: these exploratory data suggest withdrawal of higher dose calcium channel blockers should be avoided if the goal is to maintain BP control. However, low dose beta-blockers may be removed with little impact on blood pressure over 12-weeks of follow-up. Larger studies are needed to confirm these associations.
Multi-morbidity, beta-blockers, calcium channel blockers, defined daily dose, deprescribing, hypertension, older adults, polypharmacy
1663-9812
Sheppard, James P.
5468331c-e231-4103-b407-28c8161cc6d7
Lown, Mark
4742d5f8-bcf3-4e0b-811c-920e7d010c9b
Burt, Jenni
af1903e7-2bb8-464d-8e82-ec1076fdbb2e
Ford, Gary A.
58ae9408-dffd-4223-970e-67011a24af90
Hobbs, Richard
405b31a3-606d-4cec-8e05-325f49df85cc
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Sheppard, James P.
5468331c-e231-4103-b407-28c8161cc6d7
Lown, Mark
4742d5f8-bcf3-4e0b-811c-920e7d010c9b
Burt, Jenni
af1903e7-2bb8-464d-8e82-ec1076fdbb2e
Ford, Gary A.
58ae9408-dffd-4223-970e-67011a24af90
Hobbs, Richard
405b31a3-606d-4cec-8e05-325f49df85cc
Little, Paul
1bf2d1f7-200c-47a5-ab16-fe5a8756a777

Sheppard, James P., Lown, Mark, Burt, Jenni, Ford, Gary A., Hobbs, Richard and Little, Paul (2021) Blood pressure changes following antihypertensive medication reduction by drug class and dose chosen for withdrawal: exploratory analysis of data from the optimise trial. Frontiers in Pharmacology, 12, [619088]. (doi:10.3389/fphar.2021.619088).

Record type: Article

Abstract

Aims: deprescribing of antihypertensive drugs is recommended for some older patients with polypharmacy, but there is little evidence to inform which drug (or dose) should be withdrawn. This study used data from the OPTiMISE trial to examine whether short-term outcomes of deprescribing vary by drug class and dose of medication withdrawn. 

Methods: the OPTiMISE trial included patients aged ≥80 years with controlled systolic blood pressure (SBP; <150 mmHg), receiving ≥2 antihypertensive medications. This study compared SBP control, mean change in SBP and frequency of adverse events after 12-weeks in participants stopping one medication vs. usual care, by drug class and equivalent dose of medication withdrawn. Equivalent dose was determined according to the defined daily dose (DDD) of each medication type. Drugs prescribed below the DDD were classed as low dose and those prescribed at ≥DDD were described as higher dose. Outcomes were examined by generalised linear mixed effects models. 

Results: a total of 569 participants were randomised, aged 85±3 years with controlled blood pressure (mean 130/69mmHg). Within patients prescribed calcium channel blockers, higher dose medications were more commonly selected for withdrawal (90% vs. 10%). In those prescribed beta-blockers, low dose medications were more commonly chosen (87% vs. 13%). Withdrawal of calcium channel blockers was associated with an increase in SBP (5mmHg, 47 95%CI 0 to 10 mmHg) and reduced SBP control (adjusted RR 0.89, 95%CI 0.80 to 0.998) compared to usual care. In contrast, withdrawal of beta-blockers was associated with no change in SBP (-4mmHg, 95%CI -10 to 2mmHg) and no difference in SBP control (adjusted RR 1.15, 95%CI 0.96 to 1.37). Similarly, withdrawal of higher dose medications was associated with an increase in SBP but no change in BP control. Withdrawal of lower dose medications was not associated with a difference in SBP or SBP control. There was no association between withdrawal of specific drug classes and adverse events. 

Conclusions: these exploratory data suggest withdrawal of higher dose calcium channel blockers should be avoided if the goal is to maintain BP control. However, low dose beta-blockers may be removed with little impact on blood pressure over 12-weeks of follow-up. Larger studies are needed to confirm these associations.

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Optimal drug classes V6.0 02.03.21_revised - Accepted Manuscript
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Accepted/In Press date: 3 March 2021
Published date: 20 April 2021
Additional Information: Funding This work received joint funding from the National Institute for Health Research (NIHR) Oxford Collaboration for Leadership in Applied Health Research and Care (CLAHRC) at Oxford Health NHS Foundation Trust (ref: P2-501) and the NIHR School for Primary Care Research (SPCR; ref 335). JS and RM were funded by an NIHR Professorship (NIHR-RP-R2-12-015). JS now receives funding from the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z) and an NIHR Oxford Biomedical Research Center (BRC) Senior Fellowship. JB is supported by the Health Foundation™s grant to the University of Cambridge for The Healthcare Improvement Studies (THIS) Institute. THIS Institute is supported by the Health Foundation an independent charity committed to bringing about better health and health care for people in the United Kingdom. GF reports personal fees from Amgen, Bayer, Daiichi Sankyo, Medtronic and Stryker outside the submitted work. FH reports personal fees from NOVARTIS and grants from Boehringer Ingelheim and Pfizer outside of the submitted work. JM is an NIHR Senior Investigator and reports personal fees from BMS/Pfizer, outside the submitted work. RM is an NIHR Senior Investigator and reports grants from the Stroke Association and BHF, outside the submitted work. RM receives non-financial support from OMRON. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Acknowledgments The authors acknowledge the support of the Primary Care Clinical Trials Unit, staff from the NIHR CRNs including Thames Valley and South Midlands, Eastern, Wessex, West Midlands (Central and South) and West of England, and Lucy Curtin (University of Oxford) for administrative support. Rebecca Lowe (BSc, University of Oxford), Hannah Ashby (BSc, University of Oxford), Bethany Diment (PhD, University of Cambridge), Hannah Swayze (PhD, University of Oxford) and Sarah Oliver (BA, University of Southampton) worked as research facilitators recruiting and following up participants. The authors thank voluntary members of the trial steering committee and data monitoring and ethics committees. All other members of the trial steering and data monitoring committees gave their time voluntarily and were only compensated for travel expenses incurred by attendance at meetings. Participating primary care physicians were reimbursed for time and costs incurred working on the trial. The authors also thank Dr. Constantinos Koshiaris for his advice on the statistical analysis and the patients who participated in this study.
Keywords: Multi-morbidity, beta-blockers, calcium channel blockers, defined daily dose, deprescribing, hypertension, older adults, polypharmacy

Identifiers

Local EPrints ID: 447567
URI: http://eprints.soton.ac.uk/id/eprint/447567
ISSN: 1663-9812
PURE UUID: d837f036-f462-4db6-affe-7915902f34ef
ORCID for Mark Lown: ORCID iD orcid.org/0000-0001-8309-568X

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Date deposited: 16 Mar 2021 17:32
Last modified: 09 Jan 2022 03:49

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Contributors

Author: James P. Sheppard
Author: Mark Lown ORCID iD
Author: Jenni Burt
Author: Gary A. Ford
Author: Richard Hobbs
Author: Paul Little

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