Implications of the CANVAS Study in Reducing Cardiovascular Outcomes
Ameena Madan Paramasivan1, Archana Purushothaman1, Cyrus Desouza2
1Department of Internal Medicine, Diabetes Endocrinology & Metabolism, University of Nebraska Medical Center, 984120 Nebraska Medical Center, Omaha, NE, 68198-4120, USA.
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.
Insights
Sodium glucose transporter 2 inhibitors (SGLT2i) show cardiovascular benefits in type 2 diabetes mellitus (T2DM). The CANVAS program demonstrated a 14% reduction in major adverse cardiovascular events (MACE) with canagliflozin.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Cardiovascular Outcome Event Trials (CVOTs) in type 2 diabetes mellitus (T2DM) have highlighted the cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i).
- These benefits, including reduced major adverse cardiovascular events (MACE) and cardiovascular mortality, appear independent of glucose-lowering mechanisms.
- Biologically plausible theories support the macrovascular benefits observed with SGLT2i.
Purpose of the Study:
- To review and discuss the findings of the CANVAS program, a unique analysis of two aggregated cohorts treated with canagliflozin.
- To compare the results of the CANVAS program with other relevant trials, such as EMPA-REG OUTCOMES and CVD-REAL.
Main Methods:
- Analysis of two aggregated cohorts from the CANVAS program with varying durations of canagliflozin exposure.
- Comparison of CANVAS program results with EMPA-REG OUTCOMES and CVD-REAL, considering population characteristics and outcomes.
Main Results:
- The CANVAS program showed a 14% reduction in the primary MACE composite, although individual components were not significantly different from placebo.
- An initial analysis indicated a reno-protective effect of canagliflozin.
- CANVAS results showed similarities and differences compared to EMPA-REG OUTCOMES, particularly in cardiovascular mortality and adverse event profiles, potentially due to population risk profiles or drug-specific effects.
Conclusions:
- The CANVAS program provides valuable insights into the cardiovascular and renal effects of SGLT2 inhibitors in T2DM patients.
- Comparisons suggest that CANVAS findings may be generalizable to a broader population than initially studied.
- Further research is warranted to elucidate drug-specific mechanisms and optimize SGLT2i use for cardiovascular risk reduction in T2DM.
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