JAMA：减少动脉粥样硬化性血栓形成实现持续健康

　　背景  β-阻滞剂仍是心肌梗死（MI）后的标准治疗。然而，β-阻滞剂用于无MI病史的冠心病（CAD）患者、有远期MI病史的患者以及仅有CAD危险因素的患者时的益处仍未明确。

　　目的  本研究旨在评价在有既往MI病史的患者、无MI病史的CAD患者以及仅有CAD危险因素的患者中，使用β-阻滞剂与心血管事件的相关性。

　　设计、条件与患者  这项纵向、观察性研究以减少动脉粥样硬化性血栓形成实现持续健康（REACH）登记的患者为对象，将其分为3个队列：有已知既往MI病史的患者（n=14043），无MI病史的已知CAD患者（n=12012），仅有CAD危险因素的患者（n=18653）。用倾向性评分配对法完成初步分析。于2009年4月时收集末次随访数据。

　　主要转归指标  主要转归为心血管死亡、非致死性MI或非致死性卒中的组合。次要转归为主要转归加因动脉粥样硬化血栓事件或血运重建操作住院。

　　结果  在44708例患者中，21860例进入倾向性评分配对分析。在中位随访44个月（四分位数间距35~45个月）期间，在研究的所有转归方面，β-阻滞剂治疗患者与非β-阻滞剂治疗患者的事件发生率均无显著差异，即使是有既往MI病史队列的患者也是如此[分别为489（16.93%）对532（18.60%）；风险比（HR），0.90（95%CI，0.79~1.03）；P =0.14）]。在无MI病史的CAD患者队列中，β-阻滞剂治疗患者的主要转归相关事件发生率与非β-阻滞剂治疗患者相比无显著差异[391（12.94%）对405（13.55%）；HR，0.92（95%CI，0.79~1.08）；P =0.31），但次要转归[1101（30.59%）对1002（27.84%）]；比值比[OR]，1.14（95%CI，1.03~1.27）；P =0.01] 和三级住院转归[870（24.17%）对773（21.48%）；OR，1.17（95% CI，1.04~1.30）；P =0.01]的发生率较高。在仅有CAD危险因素的患者队列中，β-阻滞剂治疗患者的主要转归事件[467（14.22%）对403（12.11%）][HR，1.18（95%CI，1.02~1.36）；P =0.02]和次要转归事件[870（22.01%）对797（20.17%）；OR，1.12（95%CI，1.00~1.24）；P =0.04]发生率较高，但MI[89（2.82%）对68（2.00%）；HR，1.36（95%CI，0.97~1.90）；P =0.08]和卒中[210（6.55%）对168（5.12%）；HR，1.22（95%CI，0.99~1.52）；P =0.06]三级事件发生率与非β-阻滞剂治疗患者无显著差异。然而，对于有近期（≤1年）MI病史患者，β-治疗与次要转归发生率较低相关[OR，0.77（95% CI，0.64~0.92）]。

　　结论  在这项针对仅有CAD危险因素的患者、有已知既往MI病史的患者或已知无MI病史的CAD患者的观察性研究中，β-阻滞剂治疗并未降低复合心血管事件的危险。

β-Blocker Use and Clinical Outcomes in Stable Outpatients With and Without Coronary Artery Disease

Context  

β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear.

Objective  

To assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD.

Design, Setting, and Patients  

Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009.

Main Outcome Measures  

The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure.

Results  

Among the 44 708 patients, 21 860 were included in the propensity score–matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92]).

Conclusion  

In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.