Antihypertensive Medication Reduction vs. Usual Care in Hypertensive Elderly
- Withdrawal of antihypertension drugs can be done safely over a 12-week period in persons aged ≥80 years.
- The modest but significant rise in sBP and dBP at 12 weeks had no impact on clinical outcome albeit there were more adverse events in those with withdrawal.
- The study does not suggest that antihypertensive medication withdrawal is an appropriate strategy in the very elderly without clear indications.
Is antihypertensive medication reduction possible without significant changes in systolic blood pressure (sBP) control or adverse events during 12-week follow-up?
The OPTIMISE (Optimising Treatment for Mild Systolic Hypertension in the Elderly) study was a randomized, unblinded, noninferiority trial conducted in 69 primary care sites in England. Participants, whose physician considered them appropriate for medication reduction, were aged ≥80 years, had sBP <150 mm Hg, and were receiving ≥2 antihypertensive medications. Participants enrolled between April 2017 and September 2018, and underwent follow-up until January 2019. All were randomized (1:1 ratio) to a strategy of removal of one drug [intervention], n = 282) or usual care (control, n = 287), in which no medication changes were mandated. BP was measured using the BpTRU in the office setting at a 4-week safety visit for the intervention group and both at 12 weeks. The primary outcome was sBP <150 mm Hg at 12-week follow-up. Prespecified noninferiority margin was a relative risk (RR) of 0.90. Secondary outcomes included the proportion maintaining medication reduction and differences in sBP, frailty, quality of life, adverse effects, and serious adverse events. Reinstated treatment was recommended for sBP >150 mm Hg or dBP >90 mm Hg for >1 week, for adverse events, or signs of accelerated hypertension.
Among 569 patients randomized (mean age, 84.8 years; 276 [48.5%] women; median of two antihypertensive medications prescribed at baseline), 534 (93.8%) completed the trial. Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker was used in 85%, calcium channel blocker in 68%, beta-blocker in 40%, and statin in 33%. Over 30% had chronic kidney disease, 15% atrial fibrillation, and 21% heart disease. Overall, 86.4% patients in the intervention group and 236 (87.7%) patients in the control group had a sBP <150 mm Hg at 12 weeks (adjusted RR, 0.98). Of seven prespecified secondary endpoints, five showed no significant difference. Medication reduction was sustained in 187 (66.3%) participants at 12 weeks. Mean change in sBP was 3.4 mm Hg (95% CI, 1.1-5.8 mm Hg) and adjusted mean difference in change in dBP corrected for baseline was 2.2 mm Hg (95% CI, 0.9-3.6 mm Hg) higher in the intervention group compared with the control group. Twelve (4.3%) participants in the intervention group and seven (2.4%) in the control group reported ≥1 serious adverse event (adjusted RR, 1.72; 95% CI, 0.7-4.3).
Among older patients treated with multiple antihypertensive medications, a strategy of medication reduction, compared with usual care, was noninferior with regard to sBP control at 12 weeks. The findings suggest that antihypertensive medication reduction in some older patients with hypertension is not associated with substantial change in blood pressure control, although further research is needed to understand long-term clinical outcomes.
It would seem the study was designed to determine the safety of a large trial to test the utility of partial antihypertensive medication reduction in the very elderly. I agree with the authors who in discussion expressed concern that “sBP was increased in the medication reduction group and therefore, potential benefits of reducing medication need to be balanced against possible harms from increased risk of cardiovascular disease in the longer term.” Twenty-four-hour ambulatory monitoring is used extensively in England. It is surprising this was not used to provide more information, particularly night-time pressure, which is more highly predictive of outcome than daytime, 24-hour, and office. Whether the physicians or patients were provided an incentive for participation was not mentioned.
Keywords: Antihypertensive Agents, Angiotensin-Converting Enzyme Inhibitors, Adrenergic beta-Antagonists, Atrial Fibrillation, Blood Pressure, Blood Pressure Determination, Blood Pressure Monitoring, Ambulatory, Calcium Channel Blockers, Frail Elderly, Geriatrics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kidney Diseases, Primary Prevention, Quality of Life
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