Influence of chronic kidney disease on presentation, treatment and outcome in patients with coronary artery disease

Sammanfattning: Background. About one third of patients with myocardial infarction (MI) have renal dysfunction (RD). Concomitant coronary artery disease (CAD) and RD is accompanied by a markedly higher risk of death and subsequent cardiovascular (CV) events. The aims of this thesis were to examine the association between degree of RD, mortality and subsequent CV events in patients with stable CAD, to evaluate outcomes of different medical- and interventional treatment regimens in relation to renal function in patients with MI or undergoing percutaneous coronary intervention (PCI), as well as to study various biomarkers and their associations to RD and long-term outcomes in patients with MI. Methods and results. Study I: We used the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry to study the associations between renal function, death and CV outcomes in patients undergoing coronary angiography due to stable CAD. Despite adjusting for clinical background, risk factors, co- morbidities, severity of CAD and mode of revascularization, patients with RD had a significantly higher risk of death, subsequent MI readmission and heart failure hospitalization compared to patients without RD. Study II: Follow-up data in MI survivors enrolled in the SWEDEHEART was used to study the association between ticagrelor versus clopidogrel and death, MI or stroke and the risk of bleeds. Ticagrelor as compared with clopidogrel, was associated with lower risk for CVD outcomes and a higher bleeding risk in patients with normal- and moderately reduced renal function. In patients with severe RD, bleeds were more abundant in patients and the benefits less clear. Study III: Observational SWEDEHEART study, that compared the 1-year risk of in-stent restenosis and stent thrombosis in patients treated with coronary artery stenting using either bare metal- (BMS) or newer generation drug eluting stents (n-DES), in relation to renal function. N-DES, as compared with BMS, was associated with a lower 1-year risk of in-stent restenosis and stent thrombosis in patients with normal- and moderately reduced renal function, whereas no differences were observed between stent type and stent events in patients with severe RD. Study IV: SWEDEHEART was utilized for blood sample collection and prospective long-term follow up in 1,098 MI patients. Samples were saved in the SWEDEHEART-biobank and subsequently an untargeted analysis of 175 different biomarkers was conducted to study associations with RD, subsequent death, MI readmission and heart failure hospitalization. Six of the strongest biomarkers for RD also shared a strong variable importance for the studied long-term outcomes. Conclusion. RD is a strong and independent marker of worse outcomes in patients with CAD. Other unknown factors that were not possible to adjust for may play an important role for the risk of adverse outcomes observed in CAD patients with RD. In patients with no- or moderate RD, ticagrelor versus clopidogrel and the choice of coronary stent type were associated with higher risk of bleeds, lower risk of death, stroke or MI, as well as lower risk of stent events, respectively. However, in patients with severe RD no beneficial effects were observed following the same treatment regimens. The identification of six biomarkers with strong mutual associations with both RD and CV outcomes, may indicate the underlying mechanisms that may contribute to the poor prognosis seen in patients with concomitant MI and RD.