Withdrawal of antihypertensive drugs in older people

Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, and heart failure, as well as chronic kidney disease, cognitive decline, and premature death. Overall, the use of antihypertensive medications has led to a reduction in cardiovascular disease, morbidity rates, and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions and drug-drug interactions, and can contribute to increasing medication-related burden. As such, discontinuation of antihypertensives may be considered appropriate in some older people.

To evaluate the effects of withdrawal of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults.

For this update, we searched the Cochrane Hypertension Specialised Register, CENTRAL (2022, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO ICTRP, and ClinicalTrials.gov up to October 2022. We also conducted reference checking and citation searches, and contacted study authors to identify any additional studies when appropriate. There were no language restrictions on the searches.

We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years of age and over). Eligible participants were living in the community, residential aged care facilities, or based in hospital settings. We included trials evaluating the complete withdrawal of all antihypertensive medication, as well as those focusing on a dose reduction of antihypertensive medication.

We compared the intervention of discontinuing or reducing the dose of antihypertensive medication to continuing antihypertensive medication using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables, and Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes were mortality, myocardial infarction, and the development of adverse drug reactions or adverse drug withdrawal reactions. Secondary outcomes included hospitalisation, stroke, blood pressure (systolic and diastolic), falls, quality of life, and success in withdrawing from antihypertensives. Two review authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment.

We identified no new studies in this update. Six RCTs from the original review met the inclusion criteria and were included in the review (1073 participants). Study duration and follow-up ranged from 4 weeks to 56 weeks. Meta-analysis of studies showed that discontinuing antihypertensives, compared to continuing, may result in little to no difference in all-cause mortality (OR 2.08, 95% CI 0.79 to 5.46; P = 0.14, I² = 0%; 4 studies, 630 participants; low certainty of evidence), and that the evidence is very uncertain about the effect on myocardial infarction (OR 1.86, 95% CI 0.19 to 17.98; P = 0.59, I² = 0%; 2 studies, 447 participants; very low certainty of evidence). Meta-analysis was not possible for the development of adverse drug reactions and withdrawal reactions; the evidence is very uncertain about the effect of antihypertensive discontinuation on the risk of adverse drug reactions (very low certainty of evidence), and the included studies did not assess adverse drug withdrawal reactions specifically. One study reported on hospitalisations; discontinuing antihypertensives may result in little to no difference in hospitalisation (OR 0.83, 95% CI 0.33 to 2.10; P = 0.70; 1 study, 385 participants; low certainty of evidence). Meta-analysis showed that discontinuing antihypertensives may result in little to no difference in stroke (OR 1.44, 95% CI 0.25 to 8.35; P = 0.68, I² = 6%; 3 studies, 524 participants; low certainty of evidence). Blood pressure may be higher in the discontinuation group than the continuation group (systolic blood pressure: MD 9.75 mmHg, 95% CI 7.33 to 12.18; P < 0.001, I² = 67%; 5 studies, 767 participants; low certainty of evidence; and diastolic blood pressure: MD 3.5 mmHg, 95% CI 1.82 to 5.18; P < 0.001, I² = 47%; 5 studies, 768 participants; low certainty of evidence). No studies reported falls. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias).

The main conclusions from the 2020 review still apply. Discontinuing antihypertensives may result in little to no difference in mortality, hospitalisation, and stroke. The evidence is very uncertain about the effect of discontinuing antihypertensives on myocardial infarction and adverse drug reactions and adverse drug withdrawal reactions. Discontinuing antihypertensives may result in an increase in blood pressure. There was no information about the effect on falls. The evidence was of low to very low certainty, mainly due to small studies and low event rates. These limitations mean that we cannot draw any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for the use of antihypertensive medications, such as those with frailty, older age groups, and those taking polypharmacy, and measure clinically important outcomes such as adverse drug events, falls, and quality of life.