無高血壓並發症的非心髒手術患者長期使用β受體阻滯劑相關嚴重不良心血管事件風險如何?近期發表於《美國醫學會雜誌•內科學》(JAMA Intern Med)的一項回顧性分析研究對上述問題進行了解答。

研究者們對丹麥無並發症高血壓隊列患者的入院和出院藥物使用記錄進行了分析，這些患者至少接受兩種抗高血壓藥物治療(β受體阻滯劑、利尿劑、鈣離子拮抗劑或腎素-血管緊張素阻斷劑)，並於2005年至2011年間接受了非心髒手術。以術前120天間至少接受一份處方治療定義為明確藥物使用。主要轉歸為術後30天內(包括手術當天)嚴重不良心血管事件(MACE)和全因死亡率。對四項研究藥物的八個可能組合進行了評價，以RAS抑製劑和噻嗪類指定為參考類別治療的患者。

結果顯示，共納入了55320例接受非心髒手術的高血壓患者，其中接受β受體阻滯劑治療的患者共14644例。β受體阻滯劑治療組30天MACE和死亡發生率分別為1.32%和1.93%，而其他藥物治療組的上述發生率分別為0.84%和1.32%(P均< 0.001)。

在兩種藥物聯合應用方案中，與RAS阻滯劑聯合噻嗪類藥物相比，含β受體阻滯劑的聯合應用與患者MACE風險增加有關，與RAS阻斷劑、鈣拮抗劑和利尿劑聯用的比值比(OR)分別為2.16、2.17和1.56。傷害數(NNH)在至少70歲、男性和接受急診手術的患者中尤其明顯。

該研究結果表明，與其他類別抗高血壓藥物相比，含有β受體阻滯劑的兩種降壓藥物聯合治療方案可在統計學上顯著增加非心髒手術患者30天內的MACE和死亡率。這與當前指南推薦的不盡相同。這提示臨床醫生應對適宜患者和在適宜情況下使用圍術期β首體阻滯劑。

相關閱讀：非心髒手術患者圍術期β受體阻滯劑應用中國專家建議

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.