Optimizing lipid-lowering therapy for acute coronary syndrome using a decision support system: insights from a cluster randomized trial

Aims Lipid-lowering therapy (LLT) after acute coronary syndrome (ACS) typically follows stepwise intensification, delaying use of combination therapies and low-density lipoprotein cholesterol (LDL-C) goal attainment. We assessed whether access to a decision support system (DSS) altered the intensity of LLT prescribing vs. standard-of-care (SoC). Methods and results Pragmatic, multinational, parallel 1:1 cluster-randomized controlled trial of ACS patients comparing mandatory access to a DSS (providing estimates of cardiovascular events and benefits from different LLT scenarios) to SoC. The primary endpoint was the proportion receiving intensified monotherapy or initiated/escalated combination LLT by Week 16 compared to pre-admission LLT; secondary endpoints included individual components of the primary endpoint, proportions at goal (LDL-C < 1.4 mmol/L), and timing of LLT escalations. 42 sites from UK, Italy, and Spain were randomized, enrolling 1139 participants, 79% male, median age 62 years (IQR: 55, 69), 84% without prior CVD, 69% LLT-naïve at admission, and median admission LDL-C 3.0 mmol/L (IQR: 2.46, 3.75). The primary endpoint was met in 71.7% (DSS) vs. 65.7% (SoC) and risk ratio (RR) 1.11 (95%CI:0.92–1.33, P = 0.29). Intensification of monotherapy occurred in 9.0% vs. 13.1% (RR: 0.68, 95%CI: 0.46– 1.00), combination LLT in 61.6% vs. 50.6% (RR: 1.35, 95%CI: 0.93–1.98). LDL-C goal achievement was 54.8% vs. 50.3% (RR 1.06, 95%CI: 0.88–1.28), with LLT escalation before discharge in 64.8% vs. 60.7%. Conclusion Access to a DSS, in hospitals managing ACS, did not improve LLT intensification within 16 weeks or LDL-C goal attainment but revealed a favourable trend towards earlier combination LLT use, which merits larger, longer studies in other settings. Lay Summary The ZODIAC trial investigated whether a computer-based decision support system (DSS) could assist doctors over 16 weeks in selecting treatments more effective at lowering cholesterol for patients who suffered a heart attack within the last 72 h, across 42 hospitals in the UK, Italy, and Spain.