Berni Ellen, de Voogd Hanka, Halcox Julian P, Butler Christopher C, Bannister Christian A, Jenkins-Jones Sara, Jones Bethan, Ouwens Mario, Currie Craig J
Global Epidemiology, Pharmatelligence, Cardiff, UK.
Mylan, Weesp, The Netherlands.
BMJ Open. 2017 Jan 23;7(1):e013398. doi: 10.1136/bmjopen-2016-013398.
To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics.
Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication.
Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES).
Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998-2012 and eligible for data linkage to HES.
The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality.
Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22.
CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics.
确定与其他抗生素相比，使用克拉霉素治疗呼吸道感染是否会增加心血管（CV）事件、心律失常或全因死亡率的风险。
回顾性队列设计，比较克拉霉素单药治疗下呼吸道感染（LRTI）或上呼吸道感染（URTI）与其他抗生素单药治疗相同适应症的情况。
来自英国临床实践研究数据链的常规初级保健数据和医院事件统计（HES）的住院患者数据。
1998年至2012年期间年龄≥35岁且接受LRTI或URTI抗生素单药治疗且有资格与HES进行数据关联的患者。
主要结局指标为：与克拉霉素相比，常用抗生素在开始治疗后37天内首次发生CV事件的调整风险。其次，首次发生心律失常和全因死亡率的37天调整风险。
在700689例符合CV分析条件的LRTI治疗中，有2071例CV事件（未调整事件发生率：每10000次治疗29.6例）。在691998例符合条件的URTI治疗中，有688例CV事件（每10000次治疗9.9例）。在LRTI和URTI中，克拉霉素与所有其他抗生素联合使用的CV风险无显著差异：OR分别为1.00（95%CI 0.82至1.22）和0.82（0.54至1.25）。LRTI中与克拉霉素相比的调整后CV风险范围为OR=1.42（头孢氨苄；95%CI 1.08至1.86）至0.92（多西环素；0.64至1.32）；在URTI中，范围为1.17（阿莫西林克拉维酸；0.68至2.01）至0.67（红霉素；0.40至1.11）。LRTI中与克拉霉素相比的调整后死亡率风险范围为0.42至1.32；在URTI中，范围为0.75至1.43。对于心律失常，LRTI中的调整后风险范围为0.68至1.05；在URTI中，范围为0.70至1.22。
LRTI后发生CV事件的可能性高于URTI。按特定适应症分析时，与克拉霉素相关的CV风险与其他抗生素无差异。
