The OPTIMATE Multi-centre Clinical Trial: A Definitive Intervention to Reduce Clinically Important Adverse Effects of Polypharmacy in Multimorbid Older Adults

Abstract Background Older patients with multimorbidity and polypharmacy experience excess adverse drug reactions which contribute to frequent emergency department (ED) attendance, unscheduled readmission and increased mortality. Implementing medication optimization strategies through STOPP/START criteria and drug-drug interaction (DDI) avoidance could mitigate these adverse clinical outcomes. Methods We designed a comprehensive medication-optimizing definitive intervention (DI) based on STOPP/STARTv3 criteria and Stockley’s®DDI checker and evaluated it by randomized clinical trial in 3 large university hospitals. We enrolled 636 older patients (mean age=80.3, 49.5% female) with ≥3 chronic conditions and polypharmacy (≥5 daily medications) admitted acutely in 2023-24. Patients were randomized to standard pharmaceutical care arm (n=217), physician-delivered-DI arm (n=210) or pharmacist-delivered-DI arm (n=209). For DI patients, written and verbal medication optimization advice was delivered to senior attending doctors at admission and pre-discharge. Prioritized STOPP/STARTv3/Stockley’s®DDI medication advice was further discussed with DI-arm patients’ general practitioners at 10+/-3 days post-discharge. Primary endpoints determined at 30+/-7 days (T4) and 90-180 days (T5) post-discharge were ED attendance, readmission and all-cause mortality. Composite endpoints included (i) ED attendance, readmission or all-cause mortality, and (ii) ED attendance or readmission. Data were evaluated by logistic regression analysis with results expressed as odds ratios (OR’s) with 95% confidence intervals (CI’s). Results Both composite endpoints (i) and (ii) were significantly reduced in the combined DI arms versus controls (adjusted OR=0.68 [95%CI 0.46-0.99], p<0.05; adjusted OR = 0.65 [95%CI 0.44-0.96], p=0.03 respectively). Composite endpoint (i) was also significantly reduced in the pharmacist-delivered DI arm versus controls at T5 (adjusted OR=0.59 [95%CI 0.37-0.94], p=0.03). ED attendance was significantly reduced at T4 in the physician-delivered DI arm versus controls (adjusted OR=0.53 [95%CI 0.28-0.98], p<0.05). We found no significant endpoint differences between the two DI arms. Conclusion Implementing clinically relevant STOPP/STARTv3 inappropriate prescribing criteria and Stockley’s® DDI recommendations reduced adverse clinical outcomes in older multimorbid patients with polypharmacy.