Pharmacotherapy for hypertension in adults 60 years or older.

Rationale: This is the third update of a review that was originally published in 1998 and updated in 2009 and 2019. Hypertension increases with age, most rapidly over age 60. It is important to know the benefits and harms of antihypertensive treatment for hypertension in this age group, as well as separately for people 60 to 79 years old and for people 80 years or older.

Objectives: Primary objective • To assess the effects of antihypertensive drug treatment as compared with placebo or no treatment on all-cause mortality for people 60 years and older with hypertension defined as systolic blood pressure (SBP) > 140 mmHg or diastolic blood pressure (DBP) > 90 mmHg, or both. Secondary objectives • To assess the effects of antihypertensive drug treatment as compared with placebo or no treatment on cardiovascular-specific morbidity and mortality in people 60 years and older with hypertension defined as SBP > 140 mmHg or DBP > 90 mmHg, or both. • To assess the rate of withdrawal due to adverse effects of antihypertensive drug treatment as compared with placebo or no treatment in people 60 years and older with hypertension defined as SBP > 140 mmHg or DBP > 90 mmHg, or both.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to June 2024: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, WHO ICTRP, and ClinicalTrials.gov. We contacted the authors of relevant papers regarding further published and unpublished work.

Eligibility criteria: RCTs of at least one year's duration comparing antihypertensive drug therapy versus placebo or no treatment and providing morbidity and mortality data for people 60 years and older with hypertension defined as blood pressure greater than 140/90 mmHg.

Outcomes: Outcomes assessed were all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity and mortality, coronary heart disease morbidity and mortality, and withdrawal due to adverse effects.

Risk of bias: Two review authors independently assessed risk of bias in the included studies using the Cochrane RoB 1 tool.

Synthesis methods: We used RevMan for data synthesis and analyses. We based quantitative analyses of outcomes on intention-to-treat results. We used risk ratios (RRs) with 95% confidence intervals (CIs) to combine outcomes across trials using a fixed-effect model.

Included studies: This update identified no new trials and no ongoing trials. Overall, 16 trials (N = 26,795) in healthy ambulatory adults 60 years or older (mean age 73.8 years) with moderate to severe systolic and/or diastolic hypertension (average 182/95 mmHg) met the inclusion criteria. Most of these trials evaluated first-line thiazide diuretic therapy for a mean treatment duration of 3.8 years.

Synthesis of results: Antihypertensive drug treatment reduced all-cause mortality (10% with treatment versus 11% with control; RR 0.91, 95% CI 0.85 to 0.97; 13 studies, 25,932 participants; high-certainty evidence); probably reduced cardiovascular morbidity and mortality (10% with treatment versus 14% with control; RR 0.72, 95% CI 0.68 to 0.77; 15 studies, 26,747 participants; moderate-certainty evidence); probably reduced cerebrovascular mortality and morbidity (3.4% with treatment versus 5.2% with control; RR 0.66, 95% CI 0.59 to 0.74; 13 studies, 26,042 participants; moderate-certainty evidence); and probably reduced coronary heart disease mortality and morbidity (3.7% with treatment versus 4.8% with control; RR 0.78, 95% CI 0.69 to 0.88; 11 studies, 24,559 participants; moderate-certainty evidence). Withdrawals due to adverse effects may have increased with treatment (16% with treatment versus 5.4% with control; RR 2.91, 95% CI 2.56 to 3.30; 4 studies, 11,310 participants; low-certainty evidence). In a sensitivity analysis of the three trials restricted to people with isolated systolic hypertension, reported benefits were similar. We cannot rule out that the observed reduction in all-cause mortality was due mostly to a reduction in the 60- to 79-year-old participant subgroup compared with those 80 years or older. The RR for all-cause mortality in those 60 to 79 years old was 0.86 (95% CI 0.79 to 0.95; 9 studies, 19,017 participants) compared with 0.97 (95% CI 0.87 to 1.10; 8 studies, 6701 participants) in the 80 years or older subgroup, though the test for subgroup difference showed no evidence of a difference. The reduction in cardiovascular mortality and morbidity was due in large part to a reduction in cerebrovascular mortality and morbidity. The most common reason for downgrading the certainty of evidence was risk of bias, in particular incomplete outcome data and selective outcome reporting.

Authors' conclusions: Treating healthy adults 60 years or older with moderate to severe systolic or diastolic hypertension, or both, with antihypertensive drug therapy reduced all-cause mortality and probably reduced cardiovascular mortality and morbidity, cerebrovascular mortality and morbidity, and coronary heart disease mortality and morbidity. Most of the evidence pertains to a primary prevention population using a thiazide as first-line treatment. Given that no new or ongoing trials were identified in this update, the certainty of existing evidence is moderate or high, and we do not expect new trials in the future, this review is considered stable and will no longer be updated.

Funding: Internal sources. Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia. Office space. External sources. BC Ministry of Health grant to the Therapeutics Initiative. Infrastructure.

Registration: Original review (1998): Mulrow CD, Lau J, Cornell J, Brand M. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 1998, Issue 2. First update (2009): https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000028/full Second update (2019): https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000028.pub3/full.