Ameena Madan Paramasivan1, Archana Purushothaman1, Cyrus Desouza2. 1. Department of Internal Medicine, Diabetes Endocrinology & Metabolism, University of Nebraska Medical Center, 984120 Nebraska Medical Center, Omaha, NE, 68198-4120, USA. 2. Department of Internal Medicine, Diabetes Endocrinology & Metabolism, University of Nebraska Medical Center, 984120 Nebraska Medical Center, Omaha, NE, 68198-4120, USA. cdesouza@unmc.edu.
Abstract
PURPOSE OF REVIEW: In recent years, Cardiovascular Outcome Event Trials (CVOTs) in type 2 diabetes mellitus (T2DM) have demonstrated that sodium glucose transporter 2 inhibitors (SGLT2i) could reduce major adverse cardiovascular events (MACE) and cardiovascular mortality independent of a glucose lowering mechanism. SGLT2i trials reported significant results that have generated biologically plausible theories with regard to the macrovascular benefit. In this review, we have summarized and discussed the results of the CANVAS program. RECENT FINDINGS: The CANVAS program is unique as it is an analysis of two aggregated cohorts. The two cohorts were similar at baseline but had different durations of exposure to canagliflozin. It showed a 14% reduction in the primary MACE composite. However, the individual components of the MACE composite were not significantly different from placebo. Initial analysis also indicated a reno-protective effect. The results of the CANVAS program are similar overall yet different when compared to the EMPA-REG OUTCOMES trial, especially with regard to cardiovascular mortality and adverse event profile. This could possibly be due to the differences in the cardiovascular risk profile of the enrolled population in the two trials. Other possibilities include drug-specific effects and different mechanisms of lowering overall MACE. In addition, a brief comparison of CANVAS to the CVD-REAL indicates that the CANVAS trial results may apply to a larger, more generalized population than those in the CANVAS program.
PURPOSE OF REVIEW: In recent years, Cardiovascular Outcome Event Trials (CVOTs) in type 2 diabetes mellitus (T2DM) have demonstrated that sodium glucose transporter 2 inhibitors (SGLT2i) could reduce major adverse cardiovascular events (MACE) and cardiovascular mortality independent of a glucose lowering mechanism. SGLT2i trials reported significant results that have generated biologically plausible theories with regard to the macrovascular benefit. In this review, we have summarized and discussed the results of the CANVAS program. RECENT FINDINGS: The CANVAS program is unique as it is an analysis of two aggregated cohorts. The two cohorts were similar at baseline but had different durations of exposure to canagliflozin. It showed a 14% reduction in the primary MACE composite. However, the individual components of the MACE composite were not significantly different from placebo. Initial analysis also indicated a reno-protective effect. The results of the CANVAS program are similar overall yet different when compared to the EMPA-REG OUTCOMES trial, especially with regard to cardiovascular mortality and adverse event profile. This could possibly be due to the differences in the cardiovascular risk profile of the enrolled population in the two trials. Other possibilities include drug-specific effects and different mechanisms of lowering overall MACE. In addition, a brief comparison of CANVAS to the CVD-REAL indicates that the CANVAS trial results may apply to a larger, more generalized population than those in the CANVAS program.
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