BACKGROUND: Although guideline-recommended intensive lipid-lowering therapy (LLT) reduces recurrent cardiovascular events after acute coronary syndrome (ACS), timely implementation of intensive LLT and achievement of low-density lipoprotein cholesterol (LDL-C) target remain suboptimal in routine clinical practice.
OBJECTIVES: The purpose of this study was to determine whether a protocol-based implementation strategy improves timely achievement of guideline-recommended LDL-C target after ACS.
METHODS: We conducted a cluster-randomized trial involving patients with ACS. Ten centers were randomly assigned 1:1 to protocol-based or standard lipid management. In the protocol-based group, LLT was initiated or intensified during the index hospitalization according to a prespecified algorithm based on baseline LLT status and LDL-C levels using high-intensity statins, ezetimibe, and PCSK9 inhibitors. LDL-C was reassessed at 4 weeks, with treatment escalation when indicated. In the protocol-based group, an LDL-C level of approximately 55 mg/dL was used as the protocol-specified operational threshold for intensification, whereas LDL-C <70 mg/dL was the treatment goal in both groups. The primary and key secondary endpoints were achievement of LDL-C <70 mg/dL and <55 mg/dL at 6 months, respectively.
RESULTS: Between November 2024 and July 2025, 330 patients were enrolled, and 329 patients comprised the study population after 1 patient withdrew consent. The primary efficacy analysis included 315 patients with complete 6-month LDL-C data. Baseline characteristics were balanced between groups. The mean age was 69 years, 18% were women, and the median LDL-C level was 110 mg/dL. At 6 months, LDL-C <70 mg/dL was achieved in 86.4% vs 73.7% (between-group difference, 12.6 percentage points [95% CI: 3.8-21.5 percentage points]; P = 0.005); the corresponding difference was 12.8 percentage points (95% CI: -2.0 to 27.6 percentage points; P = 0.08) in a hospital-level sensitivity analysis. Similar findings were observed for LDL-C <55 mg/dL (60.8% vs 34.5%; between-group difference, 26.3 percentage points [95% CI: 18.5-34.0 percentage points]; P < 0.001). At 6 months, use of high-intensity statins, ezetimibe, and PCSK9 inhibitors was higher in the protocol-based group.
CONCLUSIONS: A protocol-based implementation strategy for early intensive LLT significantly improved achievement of the guideline-recommended LDL-C target after ACS. These findings support a structured, algorithm-based care pathway to facilitate timely initiation and intensification of LLT and improve implementation of guideline-recommended lipid management in routine clinical practice. (Brief and Protocol-Based Intensive Lipid Management in Patients with Acute Coronary Syndrome; jRCT1020240029).
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
This is a very good study assessing the effects of combined statin treatment versus standard hyperlipidemia care after ACS. The results show significant reductions in LDL levels in the interventional group, but the authors did not use an intention-to-treat approach in their statistical analysis, which is a major setback. It will be interesting to see if the observed reductions in LDL correspond to significant reductions in major cardiovascular events/mortality in a longer-term follow-up. These medications cost a lot of money; I am more interested in seeing whether use results in better clinical outcomes.
Physician rater
This is a clinically relevant and potentially impactful study showing that a protocol-based strategy improves LDL-C target attainment after ACS, particularly for LDL-C <55 mg/dL. However, only 10 centers were randomized, and the significant patient-level result for LDL-C <70 mg/dL becomes nonsignificant in the hospital-level sensitivity analysis. The authors should clarify how clustering was accounted for and whether the analysis was prespecified. Further clarification of the 4-week LDL-C reassessment, treatment intensification, and missing 6-month LDL-C data would also strengthen it. Overall, the findings are promising, but the statistical approach warrants careful consideration.
, McMaster University