COMMENTARY

Glyburide a Risk for Diabetes Patients With Emergent PCI?

Gregory A. Nichols, PhD

Disclosures

November 28, 2011

Glyburide Increases Risk in Patients With Diabetes Mellitus After Emergent Percutaneous Intervention for Myocardial Infarction – A Nationwide Study

Jørgensen CH, Gislason GH, Bretler D, et al
Int J Cardiol. 2011;152:327-331

Study Summary

Using the National Patient Registry of Denmark, the researchers identified patients aged 30 years or older admitted to Danish hospitals during 1997-2006 with a diagnosis of myocardial infarction (MI) and who had an emergent percutaneous coronary intervention (PCI), defined as PCI performed on the same date as admit date or the following day. Only patients with at least 1 prescription for glucose-lowering medications within 6 months of admission were included. These diabetes patients (n = 926) were divided into glucose-lowering treatment groups receiving oral monotherapy, oral combination therapy, or combinations of oral agents and insulin, respectively; those receiving sulfonylureas (SUs) were further subdivided into specific agents. Cox multivariable proportional hazard regression analyses adjusted for age, sex, calendar year, existing comorbidity (eg, heart failure, dysrhythmias, renal disease), and concomitant pharmacotherapy (eg, angiotensin-converting enzyme inhibitors, beta-blockers, statins) were used to estimate differences among groups. The study endpoints were cardiovascular mortality, a composite of cardiovascular mortality and nonfatal MI, and all-cause mortality, respectively. Nonfatal MI was defined as a subsequent admission with MI more than 30 days after index admission.

The adjusted Cox models showed an increased risk for cardiovascular mortality with glyburide (hazard ratio [HR], 2.91; 95% confidence interval [CI] 1.26-6.72; P = .012) compared with metformin. The risk for cardiovascular mortality and nonfatal MI (HR, 2.69; CI, 1.21-6.00; P = .016) and the risk for all-cause mortality (HR, 2.46; CI, 1.11-5.47; P = .027) were also increased in patients receiving glyburide. No other SUs demonstrated risk significantly different from metformin, and analyses grouping all SU monotherapy users together did not demonstrate an increased risk with the SU pharmacological class as a whole for cardiovascular mortality (HR, 1.48; CI, 0.75-2.92), cardiovascular mortality and nonfatal MI (HR, 1.42; CI, 0.76-2.64), or all-cause mortality (HR, 1.40; CI, 0.75-2.63). Comparisons between individual SUs showed significant differences for all 3 endpoints between glimepiride and glyburide demonstrating significant heterogeneity between the individual SUs.

Viewpoint

SUs have been suspected of increasing mortality since at least 1970.[1] The United Kingdom Prospective Diabetes Study helped calm those suspicions,[2] but reported a curious and potentially alarming association between diabetes-related deaths and SU-treated patients when metformin was added.[3]A more recent study found that patients newly treated with SUs or SUs plus metformin were at greater risk for cardiovascular outcomes, including mortality, than those treated with metformin alone.[4] Comparisons to metformin are tricky because metformin appears to have cardioprotective benefits,[3] so it is difficult to determine whether the effect associated with SUs is due to an elevated risk or is merely relational to the reduced risk associated with metformin. The present study is the first to directly implicate glyburide, a finding of considerable concern because it may be the most widely used SU in the United States. It is important to note that the study was limited to individuals with diabetes who had an emergent PCI. Furthermore, the stratification into specific SUs resulted in small cell sizes -- only 47 glyburide users were included in the analyses. Still, in light of all the previous reports of mortality risk associated with SUs, these findings deserve mention and definitely warrant further study in larger and more general samples.

Abstract

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