无高血压并发症的非心脏手术患者长期使用β受体阻滞剂相关严重不良心血管事件风险如何?近期发表于《美国医学会杂志•内科学》(JAMA Intern Med)的一项回顾性分析研究对上述问题进行了解答。

研究者们对丹麦无并发症高血压队列患者的入院和出院药物使用记录进行了分析，这些患者至少接受两种抗高血压药物治疗(β受体阻滞剂、利尿剂、钙离子拮抗剂或肾素-血管紧张素阻断剂)，并于2005年至2011年间接受了非心脏手术。以术前120天间至少接受一份处方治疗定义为明确药物使用。主要转归为术后30天内(包括手术当天)严重不良心血管事件(MACE)和全因死亡率。对四项研究药物的八个可能组合进行了评价，以RAS抑制剂和噻嗪类指定为参考类别治疗的患者。

结果显示，共纳入了55320例接受非心脏手术的高血压患者，其中接受β受体阻滞剂治疗的患者共14644例。β受体阻滞剂治疗组30天MACE和死亡发生率分别为1.32%和1.93%，而其他药物治疗组的上述发生率分别为0.84%和1.32%(P均< 0.001)。

在两种药物联合应用方案中，与RAS阻滞剂联合噻嗪类药物相比，含β受体阻滞剂的联合应用与患者MACE风险增加有关，与RAS阻断剂、钙拮抗剂和利尿剂联用的比值比(OR)分别为2.16、2.17和1.56。伤害数(NNH)在至少70岁、男性和接受急诊手术的患者中尤其明显。

该研究结果表明，与其他类别抗高血压药物相比，含有β受体阻滞剂的两种降压药物联合治疗方案可在统计学上显著增加非心脏手术患者30天内的MACE和死亡率。这与当前指南推荐的不尽相同。这提示临床医生应对适宜患者和在适宜情况下使用围术期β首体阻滞剂。

相关阅读：非心脏手术患者围术期β受体阻滞剂应用中国专家建议

Uncomplicated Hypertension Undergoing Noncardiac Surgery: Another Subgroup to Avoid Beta-Blockade?

Oct 05, 2015

Authors:

Jørgensen ME, Hlatky MA, Køber L, et al.

Citation:

Beta-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery. JAMA Intern Med 2015;Oct 5:[Epub ahead of print].

Summary By:

Prashant Vaishnava, M.D.

Study Questions:

What is the risk of major adverse cardiovascular events (MACE) associated with long-term beta-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery?

Methods:

This was a retrospective analysis of in-hospital records and out-of-hospital pharmacotherapy using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least two antihypertensive drugs (beta-blockers, thiazides, calcium channel antagonists, or renin-angiotensin [RAS] inhibitors) and undergoing noncardiac surgery between 2005 and 2011. Use of specific drugs was defined as at least one claimed prescription during the 120 days prior to surgery. The primary outcomes were MACE and all-cause mortality within 30 days of surgery (including events on the day of surgery). Eight possible combinations of the four study drugs were evaluated, with patients treated with RAS inhibitors and thiazides designated as the reference category.

Results:

A total of 55,320 hypertensive patients underwent noncardiac surgery (14,644 patients were treated with beta-blockers). The incidence of 30-day MACE and mortality was 1.32% and 1.93% in patients treated with beta-blockers compared with 0.84% and 1.32% in patients treated with other drugs only (both p < 0.001).

Beta-blocker use was associated with increased risks of MACE in two-drug combinations with RAS inhibitors (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.54-3.04), calcium antagonists (OR, 2.17; 95% CI, 1.48-3.17), and thiazides (OR, 1.56; 95% CI, 1.10-2.22), compared with the reference combination of RAS inhibitors and thiazides. The number needed to harm (NNH) was especially pronounced for patients at least 70 years old (NNH, 140; 95% CI, 86-364), men (NNH, 142; 95% CI, 93-195), and patients undergoing acute surgery (NNH, 97; 95% CI, 57-331).

Conclusions:

Compared with other classes of antihypertensive drugs, treatment with an antihypertensive two-drug regimen including a beta-blocker was associated with a statistically significant increase in the rate of MACE and death within 30 days of noncardiac surgery.

Perspective:

This is a large nationwide study that adds to the controversy about perioperative beta-blockade therapy. While current guidelines recommend continuation of perioperative beta-blocker therapy in those who are taking such treatment chronically, this is based on limited literature and there is even greater uncertainty about the initiation of beta-blockade perioperatively in those not already taking this treatment. The current analysis adds to other recent studies that caution against the use of perioperative beta-blocker therapy in select patients and settings. Indeed, antihypertensive treatment with beta-blocker may be associated with increased adverse perioperative events. However, we need more studies before we can definitively say whether this relationship is causal or simply unmeasured selection bias.