大环内酯类药物对心脏死亡和心律失常风险的影响

    中国广州中山大学第一附属医院医学博士吴书华在一份新闻稿中说：据最近发表的一项Meta分析的结果显示大环内酯类抗生素药物的使用可能会轻微增加心源性猝死或室性快速型心律失常的风险。心脏猝死和心脏死亡的绝对风险都很小,所以它应该可能对处方调配影响有限。不过,鉴于大环内酯类是最常用的抗生素类药物和数以百万计的患者每年按照处方使用这些药物,心源性猝死或室性快速型心律失常和心脏死亡的数量可能不能掉以轻心。

    吴和他的同事发表了33篇的研究涉及近2100万名参与者。潜在的研究发现通过使用MEDLINE和EMBASE数据库关键字无限制搜索相关的口服大环内酯类抗生素和严重心脏事件,这些事件报道出了相对危险度（RR）和测量的不确定性。首要的统计分析点是心源性猝死或室性快速型心律失常，次要的结果是心血管死亡和总死亡率。

    合并数据的统计分析显示患者服用大环内酯类药物心源性猝死或室性快速型心律失常风险增加(RR = 2.42;95%可信区间,1.61-3.63)。单独检查心源性猝死 (RR = 2.52;95%可信区间,1.91-3.31)和心血管死亡(RR =1.31;95%可信区间,1.06-1.62)可以看到增加了类似的风险。它们之间没有关系,然而,大环内酯类抗生素的使用和全因死亡或任何心血管事件都可以看到。大环内酯类药物风险的增加出现了变化,除了罗红霉素。

    研究者写到这些发现转化到一个预估的每100万疗程增加了118.1位额外的心源性猝死或室性快速型心律失常和38.2位的心血管死亡的绝对风险。

    研究人员写道“meta分析的结果表明,大环内酯类可能会显著增加心源性猝死或室性快速型心律失常和心血管死亡的风险但不是总死亡率”。“这要求精心设计(随机对照试验),进一步阐明大环内酯类的心血管安全。”

在相关的社论中, 特拉维夫Sourasky医疗中心萨米Viskin博士和他的以色列萨克特拉维夫大学医学院的同事们写道 ,“药物引起的心律失常”一直是制药行业几十年的问题。他们主张进一步研究识别潜在的风险因素,并认为此问题是不应该被忽视的领域。

   “陈报道的1:30000医源性心律失常死亡风险不能简单埋没在地毯下,”他们写道。“鉴于由权威机构出具的无所不在的实践指南的处理几乎是所有心脏病学的话题,是时候达成共识如何处理这些争议。”——戴夫Muoio

Macrolide exposure influences risk for cardiac death, arrhythmia

Cheng Y-J, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2015.09.029.

The use of macrolide antibiotics may be associated with a minor increase in the risk for sudden cardiac death or ventricular tachyarrhythmias, according to the results of a recently published meta-analysis.

“The absolute risks of sudden cardiac death [SCD] and cardiac death are small, so it should likely have a limited effect on prescribing practice,” Su-Hua Wu, MD, PhD, of the cardiology department at the First Affiliated Hospital at Sun Yat-Sen University, Guangzhou, China, said in a press release. “However, given that macrolides are one of the most commonly used antibiotic groups and millions of patients are prescribed these drugs annually, the total number of sudden cardiac deaths or ventricular tachyarrhythmias[VTA] and cardiac deaths may not be negligible.”

Wu and colleagues retrospectively examined a sample of 33 published studies involving almost 21 million participants. Potential studies were identified through unrestricted searches of the MEDLINE and EMBASE databases using keywords related to oral macrolide antibiotics and serious cardiac events, and were only included in the analysis if RR and measure of uncertainty were reported. The primary endpoints were SCD or VTA, and the secondary outcome was CV death and all-cause mortality.

Statistical analysis of the pooled data revealed an increased risk of SCD or VTA (RR = 2.42; 95% CI, 1.61-3.63) among patients taking macrolides. Similar increases were seen when examining SCD alone (RR = 2.52; 95% CI, 1.91-3.31) and cardiovascular death (RR = 1.31; 95% CI, 1.06-1.62). No relationship, however, was seen between macrolide antibiotic use and all-cause death or any CV events. Risk increases varied between macrolide types, with the exception of roxithromycin.

These findings translate to an estimated absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional CV deaths per 1 million treatment courses, the researchers wrote.

“Results of this meta-analysis suggest that macrolides may be associated with significant increased risk for SCD or VTA and cardiovascular death but not for all-cause mortality,” the investigators wrote. “This calls for large well-designed [randomized controlled trials] to further elucidate the CV safety of macrolides.”

In a related editorial, Sami Viskin, MD, of the Tel Aviv Sourasky Medical Center and Sackler School of Medicine at Tel Aviv University, Israel, and colleagues wrote that “drug-induced arrhythmia” has been a continuing issue for the pharmaceutical industry for decades. They advocated for further research toward the identification of potential risk factors, and argued that the issue should not be ignored by the field.

“The 1:30,000 iatrogenic arrhythmia death risk reported by Cheng et al. cannot be simply swept under the carpet,” they wrote. “Given the omnipresence of practice guidelines issued by authoritative organizations dealing with just about every topic in cardiology, it is time for a consensus paper on how to deal with these controversies.” – by Dave Muoio