Blood Pressure Changes Following Antihypertensive Medication Reduction, by Drug Class and Dose Chosen for Withdrawal: Exploratory Analysis of Data From the OPTiMISE Trial

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for some older patients with polypharmacy, but there is little evidence to inform which drug (or dose) should be withdrawn.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the OPTiMISE trial to examine whether short-term outcomes of deprescribing vary by drug class and dose of medication withdrawn.Methods: The OPTiMISE trial included patients aged ≥80 years with controlled systolic blood pressure (SBP; 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after 12 weeks in participants stopping one medication vs. usual care, by drug class and equivalent dose of medication withdrawn.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 generalized linear mixed effects models.Results: A total of 569 participants were randomized, aged 85 ± 3 years with controlled blood pressure (mean 130/69 mmHg). 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 (5 mmHg, 95%CI 0–10 mmHg) and reduced SBP control (adjusted RR 0.89, 95%CI 0.80–0.998) compared to usual care. In contrast, withdrawal of beta-blockers was associated with no change in SBP (−4 mmHg, 95%CI −10 to 2 mmHg) and no difference in SBP control (adjusted RR 1.15, 95%CI 0.96–1.37). 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.Conclusion: 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.

Strategies for Identifying Patients for Deprescribing of Blood Pressure Medications in Routine Practice: An Evidence Review

“…For example, medications that are not recommended for older adults, such as loop diuretics, aldosterone antagonists, centrally acting antihypertensives, peripheral vasodilators, and alpha-blockers, could be the first to be stopped. Among commonly used drugs, medications could be stopped according to effectiveness in the older population, with beta-blockers being considered for withdrawal first, followed by thiazide and thiazide-like diuretics or ACE inhibitors/angiotensin II receptor blockers, and finally, calcium channel blockers [ 48 ].…”

Antihypertensive treatment in people of very old age with frailty: time for a paradigm shift?

“…The Dutch Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) RCT [52] assessed whether discontinuation of antihypertensive drugs in 385 people aged at least 75 (mean 81.3 years), with mild cognitive impairment without serious cardiovascular disease (CVD), improved cognitive, psychological and general daily functioning. The participants had systolic BP ≤160 mmHg (≤140 mmHg if a history of diabetes, peripheral artery disease, myocardial infarction, or coronary reperfusion procedure) and either dementia, heart failure, or a limited life expectancy.…”

Antihypertensive Deprescribing in Older Adults: a Practical Guide

“…Among the most commonly used drugs, beta-blockers could be the first to stop, followed by thiazide and thiazide-like diuretics, ACE inhibitor/Angiotensin II receptor blockers (2 nd line therapy for hypertension in older people) and finally calcium channel blockers (1 st line therapy for hypertension in older people) [ 9 ]. Such an approach is supported by a recent secondary analysis of a randomised controlled trial [ 35 , 36 ], which showed that withdrawal of beta-blockers was associated with no change in systolic blood pressure, whereas withdrawal of calcium channel blockers was associated with an increased risk of uncontrolled blood pressure at 12-week follow-up [ 36 ]. This same analysis also suggested that removal of low dose medications may be associated with smaller increases in blood pressure at follow-up [ 36 ].…”

“…Such an approach is supported by a recent secondary analysis of a randomised controlled trial [ 35 , 36 ], which showed that withdrawal of beta-blockers was associated with no change in systolic blood pressure, whereas withdrawal of calcium channel blockers was associated with an increased risk of uncontrolled blood pressure at 12-week follow-up [ 36 ]. This same analysis also suggested that removal of low dose medications may be associated with smaller increases in blood pressure at follow-up [ 36 ]. Withdraw medication Antihypertensives should be withdrawn in order of preference for deprescribing, one at a time at 4-week intervals.…”