Supplementary Material for: Optimizing post-acute coronary syndrome (ACS) dyslipidemia management: Insights from the North American Acute Coronary Syndrome ACS Reflective III

Background: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aims to objectively investigate this evidence-to-practice care gap. Specifically, we aim to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies.

Methods: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1-12 months post-event from 27 Canadian and United States (U.S.) sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/U.S. guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions were provided to each physician.

Results: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% ¬¬¬¬-female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After one year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3-12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3-6 months] to 1.87 mmol/L [6-12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3-6 months] to 53.4% [6-12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost.

Conclusion: Although most patients post-ACS are on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this may be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

背景：尽管已有现行临床实践指南，但仍有大量急性冠脉综合征（ACS）患者未能达到指南推荐的低密度脂蛋白胆固醇（LDL-C）控制目标。本研究旨在客观探究这一循证实践与临床执行之间的照护差距。具体而言，本研究旨在明确需额外启用降脂治疗的场景，并分析指南推荐疗法未被处方的原因。

方法：本研究纳入2018年9月至2020年10月期间，来自加拿大及美国（U.S.）共27家研究中心、发病后1~12个月入组的急性冠脉综合征患者。入组标准为：接受最大耐受剂量他汀类药物±依折麦布治疗（包括对≥2种他汀类药物不耐受者）后，低密度脂蛋白胆固醇（LDL-C）仍≥1.81 mmol/L（70 mg/dL）。所有入组患者在发病后12个月内接受3次随访。本研究主要评估指标包括：未达到加拿大/美国指南推荐LDL-C控制目标的患者比例、符合额外降脂治疗指征的患者数量，以及存在治疗指征时未升级降脂方案的原因。研究人员向每位医师提供了个体患者数据及综合临床实践反馈，其中包含指南推荐的治疗强化建议。

结果：本先导研究共纳入248例患者（中位年龄64岁[四分位间距57, 73]，女性占31.5%，ST段抬高型心肌梗死[STEMI]患者占27.4%）。首次随访时，75.4%的患者接受了高强度他汀类药物治疗。在完成全部3次随访的患者中，18.5%的患者仅首次随访时测得的LDL-C高于目标阈值。随访满1年后，51.9%的患者在第2次或第3次随访时达到了LDL-C控制目标。在向医师反馈其参与研究的个体患者需遵循指南进行LDL-C调节治疗的提醒后，研究人员观察到，3~12个月期间依折麦布及前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂的使用量有所增加。这一变化与平均LDL-C水平显著降低相关（从基线的2.93 mmol/L降至3~6个月时的2.09 mmol/L，再降至6~12个月时的1.87 mmol/L），同时达到指南推荐LDL-C控制目标的患者比例也显著提升（从基线的0%升至3~6个月时的38.6%，再升至6~12个月时的53.4%）。未为患者升级依折麦布和/或PCSK9抑制剂降脂治疗的最常见原因包括：LDL-C水平接近目标值、已在使用其他降脂药物、患者拒绝治疗以及治疗成本。

结论：尽管大多数急性冠脉综合征患者术后接受了高强度他汀类药物治疗，但近50%的患者在1年随访时仍未达到指南推荐的LDL-C控制目标。此外，该高危人群的额外降脂治疗处方率偏低，这可能与多种因素相关，包括医师认知存在潜在缺口、治疗惰性、患者拒绝治疗以及治疗成本。