Abdelmoneim A S, Eurich D T, Gamble J M, Johnson J A, Seubert J M, Qiu W, Simpson S H
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Diabetes Obes Metab. 2014 Jan;16(1):22-9. doi: 10.1111/dom.12173. Epub 2013 Jul 19.
Sulfonylureas might increase the risk of adverse cardiovascular events; however, emerging evidence suggests there may be important differences amongst these drugs. Some, like glyburide, inhibit KATP channels in the heart and pancreas, while others, like gliclazide, are more likely to selectively inhibit KATP channels in the pancreas. We hypothesized that the risk of acute coronary syndrome (ACS) events would be higher in patients using glyburide compared with gliclazide.
This nested case-control study used administrative health data from Alberta, Canada. New users of glyburide or gliclazide aged ≥66 years between 1998 and 2010 were included. Cases were individuals with an ACS-related hospitalization or death. Up to four controls were matched based on birth year, sex, cohort-entry year and follow-up time. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR), controlling for baseline drug use and co-morbidities.
Our cohort included 7441 gliclazide and 13 884 glyburide users; 51.4% men, mean (s.d.) age 75.5 (6.6) years and mean (s.d.) duration of follow-up 5.5 (4.0) years. A total of 4239 patients had an ACS-related hospitalization or death and were matched to 16 723 controls. Compared with gliclazide use, glyburide use was associated with a higher risk (adjusted OR 1.14; 95% CI 1.06-1.23) of ACS-related hospitalization or death over 5.5 years (number needed to harm: 50).
In this observational study, glyburide use was associated with a 14% higher risk of ACS events compared with gliclazide use. Although the difference is small and probably to have implications at the population level rather than the individual patient or clinician, any causal inferences regarding sulfonylurea use and adverse cardiovascular risk should be tested in a large-scale randomized controlled trial.
磺脲类药物可能会增加心血管不良事件的风险；然而，新出现的证据表明这些药物之间可能存在重要差异。一些药物，如格列本脲，会抑制心脏和胰腺中的ATP敏感性钾通道（KATP通道），而其他药物，如格列齐特，则更倾向于选择性抑制胰腺中的KATP通道。我们推测，与使用格列齐特的患者相比，使用格列本脲的患者发生急性冠状动脉综合征（ACS）事件的风险更高。
这项巢式病例对照研究使用了来自加拿大艾伯塔省的行政健康数据。纳入了1998年至2010年间年龄≥66岁的格列本脲或格列齐特新使用者。病例为因ACS住院或死亡的个体。根据出生年份、性别、队列进入年份和随访时间匹配多达4名对照。使用多变量条件逻辑回归来估计调整后的比值比（OR），并对基线药物使用情况和合并症进行控制。
我们的队列包括7441名格列齐特使用者和13884名格列本脲使用者；男性占51.4%，平均（标准差）年龄75.5（6.6）岁，平均（标准差）随访时间5.5（4.0）年。共有4239名患者因ACS住院或死亡，并与16723名对照进行了匹配。与使用格列齐特相比，使用格列本脲在5.5年期间发生ACS相关住院或死亡的风险更高（调整后的OR为1.14；9�%CI为1.06 - 1.23）（伤害所需人数：50）。
在这项观察性研究中，与使用格列齐特相比，使用格列本脲发生ACS事件的风险高14%。尽管差异较小，可能在人群层面而非个体患者或临床医生层面产生影响，但任何关于磺脲类药物使用与心血管不良风险的因果推断都应在大规模随机对照试验中进行检验。
