Digitally Enabled Quality Improvement Intervention and LDL-C Control in Atherosclerotic Cardiovascular Disease: The SAPPHIRE-LDL Cluster Randomized Clinical Trial.

Importance: Bridging the low-density lipoprotein cholesterol (LDL-C) care gap in patients with established atherosclerotic cardiovascular disease (ASCVD) is challenging. Few quality improvement (QI) interventions have successfully improved patient care. Objective: To evaluate the impact of a digitally enabled, multifaceted, QI intervention on the control of LDL-C concentration in patients with ASCVD. Design, Setting and Participants: This was a pragmatic, 2-arm, cluster randomized clinical trial. A total of 28 clusters (public or private outpatient clinics) in Brazil were randomized to receive a digitally enabled QI intervention or routine practice (control). Adult patients (≥18 years) with established ASCVD were enrolled between November 2023 and December 2024 and followed up for 6 months. Intervention: The intervention comprised a structured, digitally enabled QI strategy integrating previsit screening, electronic clinical decision support algorithms, audit and feedback mechanisms, and targeted clinician and patient engagement tools embedded within routine workflows to support lipid monitoring, treatment intensification, and adherence. Main Outcomes and Measures: The primary outcome was mean LDL-C level at 6 months. Secondary outcomes included relative LDL-C change, achievement of LDL-C targets (<50 mg/dL and ≥50% reduction; to convert to millimoles per liter, multiply by 0.0259), and prescription of lipid-lowering therapies. All analyses were performed following the intention-to-treat principle and accounted for the cluster design by using a generalized estimating equations model. Results: Among 1465 enrolled patients (mean [SD] age, 62.3 [10.1] years; 894 male [61.0%]; 714 intervention; 751 control), mean (SD) LDL-C concentration at 6 months was 76.3 (37.5) mg/dL in the intervention group and 85.6 (37.1) mg/dL in the control group. The adjusted mean difference was -6.62 mg/dL (95% CI, -11.11 to -2.13 mg/dL; P = .004). Patients in the intervention group were more likely to achieve an LDL-C concentration less than 50 mg/dL (23.5% vs 13.4%; odds ratio, 1.86; 95% CI, 1.30-2.65) and a 50% or greater reduction in LDL-C concentration (18.6% vs 13.4%; odds ratio, 1.76; 95% CI, 1.27-2.43). Prescription of intensive and combination lipid-lowering therapy was significantly higher in the intervention group. No significant differences in major cardiovascular events were observed. Conclusions and Relevance: In this pragmatic cluster randomized clinical trial, a digitally enabled, multifaceted strategy produced modest LDL-C reduction and increased treatment intensification among patients with ASCVD. However, a proportion of patients had LDL-C levels that remained above recommended LDL-C targets, underscoring that the strategy tested was only partially effective in eliminating the residual care gap. Trial Registration: ClinicalTrials.gov Identifier: NCT05622929.