Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance.
Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance.
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DOI：
10.1161/circulationaha.123.066213
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发表时间：
2024-01-02
期刊：
影响因子：
37.8
通讯作者：
Nissen, Steven E.
中科院分区：
文献类型：
--
作者：
Ridker, Paul M.;Lei, Lei;Louie, Michael J.;Haddad, Tariq;Nicholls, Stephen J.;Lincoff, A. Michael;Libby, Peter;Nissen, Steven E.
在接受他汀类药物治疗至指南推荐的胆固醇水平的患者中，通过高敏C反应蛋白（hsCRP）评估的残余炎症风险至少与通过低密度脂蛋白胆固醇（LDLC）评估的残余风险一样强，是未来心血管事件的预测因子。这些关系是否存在于他汀类药物不耐受患者中，LDLC水平较高尚不确定，但对预防性治疗的选择有影响，包括bempedoic acid，一种降低LDLC和hsCRP的药物。多国CLEAR-Outcomes试验（通过Bempedoic Acid降低胆固醇，一项ACL抑制方案结局试验）将13970名他汀类药物不耐受患者随机分配至每日180 mg口服Bempedoic Acid或匹配安慰剂组，并对他们进行4组分复合事件（心肌梗死、卒中、冠状动脉血运重建或心血管死亡）和全因死亡率的随访。在调整传统危险因素和随机治疗分配后，评估基线hsCRP和LDLC增加的四分位数作为未来不良事件的预测因子。与安慰剂相比，bempedoic酸在6个月时使中位hsCRP降低21.6%，平均LDLC水平降低21.1%。基线hsCRP与主要心血管事件的主要复合终点显著相关（最高与最低hsCRP四分位数;风险比[HR]，1.43 [95% CI，1.24-1.65]）、心血管死亡率（HR，2.00 [95% CI，1.53-2.61]）和全因死亡率（HR，2.21 [95% CI，1.79-2.73]）。相比之下，基线LDLC四分位数对于主要复合心血管终点，（HR，1.19 [95% CI，1.04-1.37]），心血管死亡率为中性（HR，0.90 [95% CI，0.70-1.17]）和全因死亡率（HR，0.95 [95% CI，0.78-1.16]）。无论LDLC水平如何，hsCRP升高的患者风险均较高。在所有水平的hsCRP和LDLC中，本哌多酸在降低心血管事件方面表现出相似的疗效。在当代他汀类药物不耐受患者中，通过hsCRP评估的炎症预测未来心血管事件和死亡的风险比通过LDLC评估的高脂血症更强。与安慰剂相比，bempedoic酸在降低hsCRP和LDLC分层的心血管风险方面具有相似的疗效。URL：https://www.clinicaltrials.gov;唯一标识符：NCT 02993406。
Among patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP. The multinational CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) randomly allocated 13 970 statin-intolerant patients to 180 mg of oral bempedoic acid daily or matching placebo and followed them for a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and for all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse events after adjustment for traditional risk factors and randomized treatment assignment. Compared with placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months. Baseline hsCRP was significantly associated with the primary composite end point of major cardiovascular events (highest versus lowest hsCRP quartile; hazard ratio [HR], 1.43 [95% CI, 1.24–1.65]), cardiovascular mortality (HR, 2.00 [95% CI, 1.53–2.61]), and all-cause mortality (HR, 2.21 [95% CI, 1.79–2.73]). By contrast, the relationship of baseline LDLC quartile (highest versus lowest) to future events was smaller in magnitude for the primary composite cardiovascular end point (HR, 1.19 [95% CI, 1.04–1.37]) and neutral for cardiovascular mortality (HR, 0.90 [95% CI, 0.70–1.17]) and all-cause mortality (HR, 0.95 [95% CI, 0.78–1.16]). Risks were high for those with elevated hsCRP irrespective of LDLC level. Bempedoic acid demonstrated similar efficacy in reducing cardiovascular events across all levels of hsCRP and LDLC. Among contemporary statin-intolerant patients, inflammation assessed by hsCRP predicted risk for future cardiovascular events and death more strongly than hyperlipidemia assessed by LDLC. Compared with placebo, bempedoic acid had similar efficacy for reducing cardiovascular risk across hsCRP and LDLC strata. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993406.