Abstract
Purpose
The objective of this study was to determine if there is a doseâresponse relationship between sulfonylureas and major adverse cardiovascular events (MACE).
Methods
We conducted a retrospective cohort study among elderly patients with no history of acute coronary syndrome or stroke who initiated gliclazide or glyburide therapy between 1998 and 2010. Gliclazide and glyburide users were evaluated separately, and a highâdimensional propensity score (HDPS) was used to match patients initiating therapy with a low or high dose. A timeâdependent variable was used to further characterize exposure, which can change during followâup. Cox proportional hazard regression models were used to compare the risk of MACE between low (reference) and high doses.
Results
We identified 14,213 new users of gliclazide or glyburide (mean age, 74.7 (standard deviation 6.4)âyears; males, 52.8%; and mean followâup duration, 2.7 (standard deviation 2.9)âyears). Among gliclazide users, there was a higher risk of MACE with high compared with low dose (crude rates: 32.8 and 28.2 per 1000 personâyears, respectively), but this did not reach statistical significance (HDPSâmatched hazard ratio) 1.15; 95% confidence interval (0.96â1.38). For glyburide users, however, MACE occurred more frequently in the high compared with low dose (crude rates: 38.9 and 31.5 per 1000 personâyears, respectively; HDPSâmatched hazard ratio 1.24; 95% confidence interval 1.02â1.50).
Conclusions
Among new users of sulfonylureas, there appears to be a doseâresponse relationship between glyburide and MACE, but not for gliclazide. Copyright © 2016 John Wiley & Sons, Ltd.