Berwanger Otavio, de Barros E Silva Pedro G M, Barbosa Roberto Ramos, Precoma Dalton Bertolim, Figueiredo Estêvão Lanna, Hajjar Ludhmila Abrahão, Kruel Cleber Dario Pinto, Alboim Carolina, Almeida Adail Paixão, Dracoulakis Marianna Deway Andrade, Filho Hugo Vargas, Carmona Maria José Carvalho, Maia Lília Nigro, de Oliveira Filho João Bosco, Saraiva Jose Francisco Kerr, Soares Rafael M, Damiani Lucas, Paisani Denise, Kodama Alessandra A, Gonzales Beatriz, Ikeoka Dimas T, Devereaux Philip J, Lopes Renato D
Research Institute-Hospital do Coracao (HCOR), São Paulo, Brazil.
Research Institute-Hospital do Coracao (HCOR), São Paulo, Brazil; Brazilian Clinical Research Institute (BCRI), São Paulo, Brazil.
Am Heart J. 2017 Feb;184:88-96. doi: 10.1016/j.ahj.2016.11.001. Epub 2016 Nov 9.
Preliminary evidence suggests that statins may prevent major perioperative vascular complications.
We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days.
The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25).
In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.
初步证据表明他汀类药物可能预防围手术期主要血管并发症。
我们将648例计划进行非心脏手术且有发生主要血管并发症风险的未服用过他汀类药物的患者随机分组。患者被随机分为接受阿托伐他汀负荷剂量或安慰剂组（术前18小时内任何时间服用80毫克），随后是维持剂量40毫克（或安慰剂），在手术后至少12小时开始服用，然后40毫克/天（或安慰剂）服用7天。主要结局是30天时全因死亡率、非心脏手术后非致命性心肌损伤和中风的复合结局。
阿托伐他汀组326例患者中有54例（16.6%）出现主要结局，安慰剂组316例患者中有59例（18.7%）出现主要结局（风险比[HR]0.87，95%置信区间0.60 - 1.26，P = 0.46）。在30天的次要结局方面，全因死亡率（分别为4.3%对4.1%；HR 1.14，95%置信区间0.53 - 2.47，P = 0.74）、非致命性心肌梗死（分别为3.4%对4.4%；HR 0.76，95%置信区间0.35 - 1.68，P = 0.50）、非心脏手术后心肌损伤（13.2%对16.5%；HR 0.79，95%置信区间0.53 - 1.19，P = 0.26）和中风（0.9%对0%，P = 0.25）均未观察到显著影响。
与先前的观察性和试验数据相反，LOAD试验结果呈中性，在未服用过他汀类药物的接受非心脏手术患者中，短期围手术期使用他汀类药物并未显示主要心血管并发症减少。然而，我们证明了一项针对未服用过他汀类药物的高危患者的大型多中心双盲围手术期他汀类药物试验是可行的，应该进行该试验以明确他汀类药物在该患者群体中的疗效和安全性。
