Cardiovascular events after acute coronary syndrome with special reference to ischemic stroke

Abstract: Background: Acute coronary syndrome (ACS) encompasses acute myocardial infarction (AMI) and unstable angina (UA). It is a global major cause of morbidity and mortality in both the short and long terms. The risk for recurrent ischemic cardiovascular (CV) events and death after ACS depends on patient factors at presentation, revascularization and secondary prevention measures. Of these, ischemic stroke (IS) is a feared and potentially devastating complication that confers suffering for the individual patient and an economic burden on society. ACS and secondary prevention treatment have gone through dramatic improvements during recent decades. These improvements, together with an improved risk factor profile in the general population, have led to lower morbidity and halved mortality. ACS and IS share many risk factors. Most of our knowledge about prognosis and risk of recurrent ischemic events after ACS is based on clinical trials and it is uncertain whether these findings can be translated to the general population. Aims: The study aims were as follows: to estimate the rate, time trends, risk factors and effects on mortality of IS after an AMI during the decades that ACS and secondary prevention treatment improved; to study wether the switch from the antiplatelet agent clopidogrel to ticagrelor influenced post-AMI IS risk in patients treated with PCI, based on data from the SWEDEHEART register; and to estimate the long-term rate of subsequent CV events after ACS in an unselected cohort of ACS patients, based on the ACS-population in the Nurse-based Age- independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome (NAILED-ACS) study. Methods: In papers I–IV, data from the SWEDEHEART register were merged with the Swedish National Patient Register (NPR) to identify patients with AMI and subsequent ischemic stroke. In paper V, data were obtained from the NAILED-ACS study. Survival analysis with Kaplan–Meier estimates and hazard ratios for risk factors with Cox proportional hazards regression models were calculated in all five studies. When appropriate, propensity scores and competing risk analyses were used to adjust for baseline differences and a high overall mortality rate, respectively. Results: The overall IS rates at 30 days and 1 year after AMI were 2.1 and 4.1% respectively, during the study period (1998–2008). The rate of IS after AMI decreased over time, both at 30 days and at 1 year, with relative risk reductions (RRRs) of 11% at 30 days and 20% at 1 iii year respectively, when comparing the beginning and end of the study period. AMI complicated by IS within 1 year had a higher mortality rate than AMI without IS (36.5 vs. 18.3%). The mortality rates decreased during 1998– 2008, by 9.4% in patients with IS and 7.5% in those without IS.The introduction of dual antiplatelet therapy (DAPT) with ticagrelor instead of clopidogrel was associated with a 21% relative risk reduction of IS within 1 year after AMI in patients treated with PCI. The rate of recurrent CV events (CV death, AMI and IS) after ACS during the first year was 10.3% and remained high during a median follow-up time of 4.7 years, at 28.6%.Predictors of increased risk of recurrent ischemic events were older age, female sex, previously established CV and cerebrovascular disease, hypertension, atrial fibrillation, diabetes mellitus, heart failure and renal disease. Reperfusion and revascularization procedures in the acute phase as well as evidence-based secondary prevention treatment were associated with a protective effect against recurrent ischemic events. Conclusion: The results reported in this thesis indicate an overall high rate of recurrent CV events after ACS based on a contemporary, unselected population of ACS patients. IS a relatively rare, but serious complication after AMI that confers a substantially increased mortality risk. The rate and mortality risk of IS after AMI have decreased over time. Improved, evidence-based treatment, both in the acute phase and in the long term, has most likely reduced the post-ACS risk of recurrent ischemic events in general and more specifically of IS. The switch from clopidogrel to ticagrelor was associated with a small, but statistically significant reduction in IS risk in PCI-treated AMI patients.