Muhlestein Joseph B, Anderson Jeffrey L, Horne Benjamin D, Carlquist John F, Bair Tami L, Bunch T Jared, Pearson Robert R
Cardiovascular Department, LDS Hospital, Salt Lake City, Utah 84143, USA.
Am J Cardiol. 2004 Nov 1;94(9):1107-12. doi: 10.1016/j.amjcard.2004.07.074.
Statins improve survival in patients with coronary artery disease, especially those with elevated C-reactive protein (CRP). Although some randomized studies have shown a delay in statin-related survival advantage of up to 2 years, recent studies demonstrated early (<2 months) survival benefit in certain patient groups. We hypothesized that this early benefit relates to baseline CRP concentration. Patients (n = 2,924) with significant, angiographically defined coronary artery disease (>/=70% stenosis in >/=1 coronary artery) were followed for an average of 2.4 years after discharged on a statin prescription. CRP was divided into tertiles (<1.2, 1.2 to 1.7, >1.7 mg/dl), and Kaplan-Meier methods were used to determine timing of statin benefit in both the overall population and a propensity score-matched subgroup. Cox regressions (multivariable and propensity score approaches) were used to predict mortality. Statins were prescribed for 28.4% of patients. In the first CRP tertile, no early statin benefit was observed (adjusted hazard ratio 0.69, 95% confidence interval [CI] 0.30 to 1.6, p = 0.39), and survival curves separated after >2 years. However, in the second and the third tertiles, statin survival curves separated much earlier ( approximately 3 months and 1 week, respectively) and statins predicted improved survival (second tertile: hazard ratio 0.63, 95% CI 0.32 to 1.2, p = 0.17; third tertile: hazard ratio 0.35, 95% CI 0.18 to 0.67, p = 0.002). Propensity score analysis confirmed both statin benefit and early timing. Thus, statin use in patients with high CRP provides not only a larger but also a significantly earlier absolute survival benefit than statin use in patients with lower CRP. This provides further evidence of an anti-inflammatory effect of statins.
他汀类药物可提高冠心病患者的生存率，尤其是那些C反应蛋白（CRP）升高的患者。尽管一些随机研究表明，他汀类药物相关的生存优势延迟长达2年，但最近的研究显示，某些患者群体可在早期（<2个月）获得生存益处。我们推测，这种早期益处与基线CRP浓度有关。对2924例经血管造影确诊为严重冠心病（≥1支冠状动脉狭窄≥70%）的患者，在接受他汀类药物处方出院后平均随访2.4年。CRP分为三分位数（<1.2、1.2至1.7、>1.7mg/dl），采用Kaplan-Meier方法确定总体人群和倾向评分匹配亚组中他汀类药物获益的时间。采用Cox回归（多变量和倾向评分方法）预测死亡率。28.4%的患者使用了他汀类药物。在第一个CRP三分位数中，未观察到他汀类药物的早期益处（调整后的风险比为0.69，95%置信区间[CI]为0.30至1.6，p = 0.39），生存曲线在2年以上分离。然而，在第二个和第三个三分位数中，他汀类药物的生存曲线分离得更早（分别约为3个月和1周），他汀类药物可预测生存率提高（第二个三分位数：风险比为0.63，95%CI为0.32至1.2，p = 0.17；第三个三分位数：风险比为0.35，95%CI为0.18至0.67，p = 0.002）。倾向评分分析证实了他汀类药物的益处和早期获益时间。因此，与CRP水平较低的患者相比，CRP水平较高的患者使用他汀类药物不仅能获得更大的绝对生存益处，而且显著更早。这进一步证明了他汀类药物的抗炎作用。
