Myocardial infarction - Risk stratification and evaluation of therapies

Abstract: Background. Myocardial infarction (MI) remains the leading cause of death worldwide, despite several advances in acute coronary care during the last decades. This thesis assessed different risk stratification tools and evaluated interventional and pharmacological treatment strategies in high-risk patients with MI. Methods. This work comprises four studies. The first and the fourth study extracted data from national registries. The first study evaluated the prognostic value of early percutaneous coronary intervention (PCI) on mortality in 2896 patients with cardiac arrest and no signs of ST-elevation MI (STEMI) undergoing coronary angiography, while the fourth study validated the novel PRECISE-DAPT score for the prediction of post-discharge bleeding in 66295 patients with MI treated with PCI and dual antiplatelet therapy (DAPT). The second and the third study were prespecified subgroup analyses of a recent trial that randomly assigned MI patients to an anticoagulation strategy with bivalirudin or heparin during PCI in a contemporary setting, including routine radial artery access, potent P2Y12 inhibition, and rare use of glycoprotein IIb/IIIa inhibitors. The second study investigated the impact of baseline anemia on clinical outcomes in 5482 of these patients, whereas the third study compared bivalirudin to heparin monotherapy regarding clinical outcomes in 1592 elderly patients (≥75 years). Results. A total of 1271 (43.9%) of resuscitated cardiac arrest patients without STEMI had severe coronary artery stenosis (≥90%) on coronary angiography, of whom 753 (59.2%) underwent PCI but experienced a higher 30-day mortality rate compared to patients undergoing only diagnostic coronary angiography (40.9% vs 32.7%; p=0.011). After adjustments for confounders, there was no association between PCI and mortality (hazard ratio [HR] 1.07; 95% confidence interval [CI] 0.84-1.36). Baseline anemia identified a subset of MI patients undergoing PCI with a higher comorbidity burden. Anemia was associated with increased 180-day rates of death (6.9% vs 2.1%; p<0.001), myocardial reinfarction (4.3% vs 1.9%; p<0.001), major bleeding (13.4% vs 8.2%), and stroke (2.0% vs 0.7%). Results were particularly evident in patients with a hemoglobin value below 100 g/L, who had a tenfold higher mortality rate, sixfold higher MI rate, and threefold higher bleeding rate, compared to patients without anemia. Results were similar after adjustments for confounders. Elderly patients (≥75 years) had a markedly increased risk of adverse outcomes within 180 days after MI and PCI compared to younger patients (<75 years). Elderly patients who received bivalirudin or heparin had similar baseline characteristics. Bivalirudin did not reveal any benefit over heparin monotherapy, regarding 180-day mortality, myocardial reinfarction, major bleeding, stroke, or stent thrombosis. A high PRECISE-DAPT score (≥25) identified a high-risk subset of MI patients with more comorbidities and higher bleeding rates during DAPT. However, the predictive performance for major bleeding was moderate (c-statistic 0.64; 95% CI 0.63-0.66). Furthermore, the discriminatory power of the score was even more limited in patients with pre-existing risk factors for bleeding, especially for patients with advanced age (c-statistic 0.57; 95% CI 0.55-0.60), low body weight (c-statistic 0.56; 95% CI 0.51-0.61), anemia (c-statistic 0.60; 95% CI 0.58-0.63), or cancer (c-statistic 0.59; 95% CI 0.53-0.66). Conclusion. The reported findings in this research on risk stratification tools and therapies have potential implications for a more patient-tailored acute coronary care that may further improve outcomes for patients with MI.