Optimising Prescription of Treatment In older patients with Mild hypertension at Increased risk of Serious adverse Events (OPTIMISE2)

Research question

What is the effect of antihypertensive deprescribing on emergency hospital admissions and death in older adults at higher risk of adverse events?

Background

More than one in three adults aged 75+ years are prescribed =5 medications, a situation known as polypharmacy. Polypharmacy is associated with multi-morbidity, reduced independence and an increased risk of hospital admission due to adverse drug reactions. One approach to managing polypharmacy is to withdraw (deprescribe) medications where risk adverse events is high and the likelihood of benefit is small. Antihypertensives are the most frequently prescribed medication in patients with polypharmacy and although trials have shown that they reduce the risk of stroke and cardiovascular disease (CVD), very few include patients with frailty and multi-morbidity. Indeed, antihypertensives can sometimes be harmful, increasing the risk of acute kidney injury and syncope. Some clinical guidelines suggest that doctors consider deprescribing antihypertensives, where the harms outweigh the benefits, without clear evidence on how harms can be assessed. We recently completed the OPTiMISE trial, showing that antihypertensive deprescribing could be achieved without affecting systolic blood pressure (SBP) control (<150 mmHg for aged =80), and no differences in serious adverse events or health-related quality of life. However, the trial was limited to 12 weeks follow-up, so the longer term effects deprescribing remain unknown.

Aims

1. Determine whether deprescribing antihypertensives is safe and beneficial in older adults at risk of adverse events.

2. Determine whether deprescribing antihypertensives is cost -effective.

Methods

This study will be a primary care based, randomised controlled trial, enrolling 3,014 participants aged=75 years, receiving =2 antihypertensive medications with controlled SBP and moderate to severe frailty and/or high risk of falls or acute kidney injury. The trial will compare step-down antihypertensive medication reduction with usual care. The primary outcome will be a non-inferior difference (margin of 5%) in all-cause emergency hospital admissions and death at 1 year. Secondary outcomes include differences in stroke, CVD, death, all-cause hospitalisation, side effects, health-related quality of life, cognition, physical function and cost-effectiveness. If non-inferiority is demonstrated at 1 year, differences in outcomes will be further examined at 3 years. Outcomes will be determined by intention to treat, using generalised logistic mixed effects models, adjusted for baseline SBP and GP site. An economic evaluation will measure and value the cost-effectiveness of deprescribing, through a within-trial evaluation and a decision-analytic model extending over a lifetime horizon.