Stepura A. Clinical and pathogenetic substantiation of early intensive hypolipidemic therapy in patients with acute myocardial infarction.

The dissertation work was aimed at studying: the changes in the lipid state against the background of different intensity of hypolipidemic therapy, clinical course of the disease, endothelial function, myocardial remodeling and determination of tissue and myocardial blood flow by treatment of different intensity of hypolipidemic therapy in patients presenting with ST-segment elevation myocardial infarction (STEMI). Therefore, it is important and relevant to differentiate and quantify the effect of different intensity of hypolipidemic therapy on regulatory mechanisms for the introduction into the clinical practice of an individual approach to the treatment of STEMI patients.We analyzed the frequency of complications such as recurrent acute myocardial infarction (AMI), the occurrence of early post-infarction angina (EPIA), the presence of acute heart failure (AHF) at the 5th day from the onset of the disease, death and the combined endpoint (myocardial infarction relapse, EPIA, AHF on the 5th day). The study included 135 patients with STEMI. The patients were divided into 4 groups according to the method of random sampling: 26 persons were included in І who were prescribed a combination of 10 mg of atorvastatin and 10 mg of ezetimibe; ІІ consisted of 24 patients who received atorvastatin in a dose of 40 mg; ІІІ included 43 patients who were prescribed 80 mg of atorvastatin; IV consisted of 42 individuals who received a combination of 40 mg of atorvastatin and 10 mg of ezetimibe. The duration of the remote observation was 90 days. Groups of patients did not differ in clinical and anamnestic indicators, as well as concomitant therapy. The fixed combination of atorvastatin and ezetimibe had a more pronounced hypolipidemic effect compared with monotherapy. The achievement of target levels of Low-density lipoprotein (LDL) cholesterol in groups III and IV was significantly higher than in groups I and II on the 90th day of observation. Patients in group III (61%), who treat by the active lipid-lowering therapy with 80 mg of atorvastatin and 72% of patients - 40 mg atorvastatin and 10 mg ezetimibe (p<0.05) reached target levels of LDL-C. More pronounced hypolipidemic effect was noted in patients of group IV (40 mg of atorvastatin and 10 mg of ezetimib) compared with І (10 mg atorvastatin and 10 mg ezetimib) and ІІ (40 mg atorvastatin). This patients were reached the target level or reduced more than 50% of initial LDL cholesterol levels.At the 1st day the risk of recurrence of angina pain in the group with medium-intensity lipid-lowering therapy (LLT) was 8.5 times higher than group high-intensity LLT (95% CI (1.02-70.2)) and EPIA developed more often (HR 3.82 (95% CI 1.2-11.8)) and the combined end point (HR 5.1 (95% CI 1.9-13.2)), respectively. Assessing the risk of development of events in the out-of-hospital period, recurrent MI and death had higher rates (НR 6.8 (95% CI 1.1-59.1)) in patients who receiving high-intensity therapy. In patients of groups III and IV (high-intensity LLT), recovery of myocardial blood flow after stenting was significantly better than in groups I and II (p <0.001), at the same indicator TIMI. At the 90-day observation in the studied groups were revealed a significant decrease rates the events of late post-infarction dilatation in groups III and IV (by 30%), registration of dilatation in patients with high-intensity LLT compared with individuals receiving medium-intensity LLT (p<0.05). The scientific novelty consists: for the first time the effect of the early administration of different-intensity LLT to decrease LDL cholesterol levels, improve tissue blood flow, and assessed hospital and post-hospital complications in STEMI patients. The practical significance of the results obtained is that the early administration of high-intensity LLT can improve the level of myocardial blood flow after revascularization, as well as reduce complications after suffering AMI.