Optimising Prescription of Treatment In older patients with Mild hypertension at Increased risk of Serious adverse Events (OPTIMISE2): Protocol for a primary care based, open-label, randomised controlled non-inferiority trial

Background Antihypertensive treatment is effective at reducing the risk of cardiovascular disease, but is associated with adverse events, particularly in older patients with frailty. As a result, deprescribing antihypertensive medications is recommended in some clinical guidelines despite limited evidence from a few small randomised controlled trials. The aim of the OPTIMISE2 trial is to examine the safety, efficacy and cost-effectiveness of deprescribing antihypertensive treatment in older adults with controlled systolic blood pressure, who are at higher risk of adverse events. Methods The OPTIMISE2 Trial aims to enrol 3,014 participants into the trial and actively follow them up for one year. Participants are aged 75 years and above and taking two or more blood pressure lowering drugs, with controlled blood pressure readings (systolic blood pressure < 140 mmHg if aged 75–79 years or < 150 mmHg if aged 80 + years), frail and/or at a higher risk of serious drug related side-effects of hypotension, syncope and falls. The trial randomises (1:1) participants to either step-down medication reduction (withdrawal of one antihypertensive medication at a time, at four-week intervals with regular monitoring of blood pressure) or usual care (no medication reduction mandated). The choice of medications to withdraw is at the discretion of participating general practitioners or prescribers. The primary outcome is emergency hospitalisation or death within one year of randomisation. The primary objective is to determine whether antihypertensive deprescribing is non-inferior to usual care, with up to a 5% difference in the percentage of patients with an emergency hospitalisation/death. The study uses a within-trial economic evaluation and decision-analytic modelling to estimate the cost-effectiveness of deprescribing antihypertensive treatment. Discussion It is expected that these findings will inform clinical guidelines and practice about deprescribing of antihypertensive medications in older adults with frailty, who have controlled systolic blood pressure but are at higher risk of adverse events. Trial registration ISRCTN18030225. Registration Date: 19/09/2023