The primary risk factor for coronary artery disease is atherosclerosis, with inflammation playing a crucial role in the development and progression of this condition. It has now been proven that inflammation is key in the development of complications after an acute myocardial infarction. These complications can be immediate and mechanical, such as ventricular wall rupture and ventricular arrhythmia, or long-term, presenting as major cardiovascular events like heart failure.
During acute myocardial infarction (AMI), circulating high-sensitivity CRP levels increase approximately 6 hours after the onset of ischemia. CRP levels measured between 24 and 72 hours after symptom onset are a significant prognostic marker for one-year outcomes. Higher high-sensitivity CRP levels at the time of AMI are linked to more severe coronary atherosclerotic lesions seen on angiography and lower LVEF one month after the event. A serum high-sensitivity CRP concentration greater than 10 mg/L after an AMI indicates inflammation, reflecting myocardial necrosis, plaque rupture, and acute thrombosis. In patients with AMI, persistent or increasing CRP levels are strongly associated with a higher risk of all-cause and non-cardiovascular death, especially when inflammation (CRP \> 2.0 mg/L) continues for a year.
Aside from reperfusion therapy, very few pharmacological approaches have been used to reduce inflammation after AMI. One such approach was the use of colchicine in the COVERT-MI randomized, double-blind, multicenter trial. This trial compared five days of oral colchicine with a placebo and found no difference in infarct size between the groups at five days or three months, as measured by cardiac magnetic resonance imaging.
SGLT-2 inhibitors are drugs that have revolutionized the management of cardiovascular diseases, offering proven benefits for patients with heart failure and notable nephroprotective effects. However, their use after acute myocardial infarction has not yet been sufficiently established, as the only two published clinical trials so far failed to meet their primary goal of reducing hospitalizations for heart failure. Additionally, evidence of their use in post-AMI inflammation exists only in experimental studies. In experimental studies, SGLT2 global-knockout (KO) mice were used to demonstrate that dapagliflozin significantly influences cardiac fibrosis and inflammation, and markedly alters the gene expression profiles of macrophages and fibroblasts. Moreover, dapagliflozin directly inhibited macrophage-mediated inflammation, thereby suppressing cardiac fibroblast activation.
Similarly, only experimental studies have shown that semaglutide decreases elevated levels of TNF-α, IL-6, ROS, and MDA in the serum and cardiac tissues of obese mice. By lowering the expression of Cxcl2, S100a8, and S100a9 in neutrophils, semaglutide may help reduce cardiac inflammation and oxidative stress.
Therefore, the objective of this study is to compare the effects of dapagliflozin and semaglutide on inflammatory markers (hs-CRP and IL-6) in patients with acute ST-segment elevation myocardial infarction.
