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Redefining Cardiovascular (CV) Death as a Primary Endpoint Component in Cardiovascular Outcome Trials
1Department of Endocrinology, Nightingale Hospital, Kolkata, India.
Abstract:
Sodium-Glucose cotransporter-2 inhibitors (SGLT-2i) and Glucagon-like peptide 1 receptor agonists (GLP1-RA) have revolutionised the approach for modern management of type 2 diabetes in view of their outcome altering abilities. An objective component of the primary endpoints used in the Cardiovascular Outcome Trials (CVOT) is cardiovascular (CV) death. However, the reason behind the decrease in CV deaths (compared to the placebo arm) appear to arise from divergent underlying processes. A recent meta-analysis of SGLT-2i and GLP1-RA indicated that the reduction in CV death associated with the former is predominantly due to its impact on heart failure (HF), while the association with the latter is due to its effect on atherosclerotic cardiovascular disease (ASCVD). A Pearson's product- moment correlation coefficient (r) analysis was performed on SGLT-2i exposed to CVOTs, exploring the strength of the association between CV death and hospitalisation for HF (hHF) and myocardial infarction (MI). The strength of association was strongest with hHF and negative with MI. In view of these findings, it has been proposed that future CVOTs should use a more objective definition of CVD, defining well in advance the anticipated impact on CVD (either as a consequence of the reduction in HF or ASCVD).
Insights
Sodium-Glucose cotransporter-2 inhibitors (SGLT-2i) reduce cardiovascular death primarily through heart failure benefits, while Glucagon-like peptide 1 receptor agonists (GLP1-RA) impact atherosclerotic disease. Future trials need clearer cardiovascular death definitions.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Sodium-Glucose cotransporter-2 inhibitors (SGLT-2i) and Glucagon-like peptide 1 receptor agonists (GLP1-RA) are key in type 2 diabetes management.
- Cardiovascular Outcome Trials (CVOTs) assess cardiovascular (CV) death, but the mechanisms of CV death reduction differ between drug classes.
Purpose of the Study:
- To investigate the distinct mechanisms by which SGLT-2i and GLP1-RA reduce cardiovascular death.
- To analyze the association between SGLT-2i use, cardiovascular death, heart failure hospitalizations (hHF), and myocardial infarction (MI).
Main Methods:
- A meta-analysis of SGLT-2i and GLP1-RA trials was reviewed.
- Pearson's correlation coefficient (r) analysis was applied to SGLT-2i CVOT data.
Main Results:
- SGLT-2i's CV death reduction is linked mainly to decreased heart failure (HF).
- GLP1-RA's CV death reduction is associated with reduced atherosclerotic cardiovascular disease (ASCVD).
- Correlation analysis showed the strongest association between SGLT-2i and reduced hHF, with a negative association with MI.
Conclusions:
- The mechanisms driving cardiovascular death reduction differ significantly between SGLT-2i and GLP1-RA.
- Future CVOTs should adopt more precise definitions for cardiovascular death, specifying whether the benefit stems from HF or ASCVD reduction.
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