Dale Krista M, White C Michael, Henyan Nickole N, Kluger Jeffrey, Coleman Craig I
The University of Connecticut Schools of Pharmacy, Hartford, Conn 06102-5037, USA.
Am J Med. 2007 Aug;120(8):706-12. doi: 10.1016/j.amjmed.2006.07.033.
Higher intensity statin therapy reduces cardiovascular events more than lower intensity therapy, but the safety impact of higher intensity therapy is unknown. We performed a meta-analysis of randomized controlled trials comparing higher versus lower intensity therapy on liver and muscle safety.
A systematic literature search through January 2006 was conducted to identify randomized trials comparing higher versus lower intensity statin therapy meeting our criteria. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (random-effects model). Statistical heterogeneity scores were assessed with the Q statistic and L'Abbe plots. Publication bias was assessed with the Egger weighted regression and funnel plots.
Higher intensity statin therapy increased the incidence of transaminase elevations (RR 3.10 [95% Confidence Interval [CI], 0.88-7.85]) versus lower intensity statin therapy. When studies of hydrophilic and lipophilic statins were evaluated separately, higher intensity hydrophilic statin therapy increased the risk for transaminase elevations (RR 3.54 [95% CI, 1.83-6.85]), but higher intensity lipophilic therapy did not (RR 1.58 [95% CI, 0.81-3.08]). The risk of creatine kinase (CK) elevations showed a trend toward an increase (RR 2.63 [95% CI, 0.88-7.85]) with higher intensity therapy. No occurrences of CK elevations occurred in studies evaluating hydrophilic statins, whereas lipophilic statins showed an increased risk with higher intensity therapy (RR 6.09 [95% CI, 1.36-27.35]).
More aggressive statin therapy increases the incidence of transaminase elevations in clinical trials versus lower intensity therapy. Increases in transaminases may be more problematic when hydrophilic statins are used aggressively, whereas CK elevations are more problematic with higher intensity lipophilic statin therapy.
高强度他汀类药物治疗比低强度治疗能更多地降低心血管事件，但高强度治疗对安全性的影响尚不清楚。我们对比较高强度与低强度治疗对肝脏和肌肉安全性的随机对照试验进行了荟萃分析。
通过检索截至2006年1月的系统文献，以确定符合我们标准的比较高强度与低强度他汀类药物治疗的随机试验。加权平均值报告为相对风险（RR）及95%置信区间（随机效应模型）。使用Q统计量和L'Abbe图评估统计异质性得分。使用Egger加权回归和漏斗图评估发表偏倚。
与低强度他汀类药物治疗相比，高强度他汀类药物治疗增加了转氨酶升高的发生率（RR 3.10 [95%置信区间（CI），0.88 - 7.85]）。当分别评估亲水性和脂溶性他汀类药物的研究时，高强度亲水性他汀类药物治疗增加了转氨酶升高的风险（RR 3.54 [95% CI，1.83 - 6.85]），但高强度脂溶性治疗未增加（RR 1.58 [95% CI，0.81 - 3.08]）。肌酸激酶（CK）升高的风险在高强度治疗时有增加的趋势（RR 2.63 [95% CI，0.88 - 7.85]）。在评估亲水性他汀类药物的研究中未出现CK升高的情况，而脂溶性他汀类药物在高强度治疗时显示出风险增加（RR 6.09 [95% CI，1.36 - 27.35]）。
在临床试验中，与低强度治疗相比，更积极的他汀类药物治疗增加了转氨酶升高的发生率。积极使用亲水性他汀类药物时转氨酶升高可能更成问题，而高强度脂溶性他汀类药物治疗时CK升高更成问题。
