急性心肌梗死(AMI)后患者应用β受体阻滞剂治疗可改善生存，而在临床实践中，β受体阻滞剂的剂量常比在随机试验中使用的剂量低。较大剂量的β受体阻滞剂是否可增加AMI患者的生存率?对此美国学者们开展了一项多中心注册研究，结果表明，与较小剂量的β受体阻滞剂相比，使用既往随机临床试验中类似剂量的β受体阻滞剂并不增加患者的生存率。相关研究论文近期在线发表于《美国心脏病学会杂志》(J Am Coll Cardiol.)

        该研究纳入了7057例AMI连续患者，根据在随机临床试验中使用的目标β阻滞剂剂量索引出院β阻滞剂剂量，将患者分为以下四组：0%-12.5%，12.5%-25%，25%-50%，>50%。主要终点事件为至死亡时间，用多变量和倾向评分分析组间差异。

        结果显示，共有6682例患者完成随访，中位随访2.1年，91.5%出院后使用β阻滞剂(平均剂量为目标剂量的38.1%)。与未使用β阻滞剂者相比，使用所有剂量β阻滞剂组患者的死亡率较低(P< 0.0002)。

        校正多变量后，与>50%目标剂量组相比，0%-12.5%、12.5%-25%和25%-50%目标剂量组的2年死亡率危险比分别为0.862、0.799、0.963。多变量分析的扩展协变量和倾向得分分析也显示，较大剂量的β阻滞剂与较好预后无关。

        英文：Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction

Commentary by Dr. Valentin Fuster

Jeffrey J. Goldberger, MD, MBA∗; Robert O. Bonow, MD∗; Michael Cuffe, MD†; Lei Liu, PhD‡; Yves Rosenberg, MD, MPH§; Prediman K. Shah, MD‖; Sidney C. Smith, Jr., MD¶; Haris Subačius, MA∗

[-] Author Information

∗ Center for Cardiovascular Innovation and the Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 

Abstract

Background  Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy.

Objectives  This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival.

Methods  A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences.

Results  Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome.

Conclusions  These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study—Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN]: NCT00430612)

J Am Coll Cardiol. 2015;66(13):1431-1441. doi:10.1016/j.jacc.2015.07.047