Robert Edfors

Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation

IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24,317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m2 [eGFR<60]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR>30-60: event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR>15-30: event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR≤15: event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR>30-60 event rate, 6.8 for warfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR>15-30 event rate, 9.3 for warfarin vs 10.4 for no warfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR≤15 event rate, 9.1 for warfarin vs 13.5 for no warfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR>60 event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR>30-60 event rate, 53.6 for warfarin vs 69.0 for no warfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR>15-30 event rate, 90.2 for warfarin vs 117.7 for no warfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR≤15 event rate, 86.2 for warfarin vs 138.2 for no warfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

Association between the use of fondaparinux vs low-molecular-weight heparin and clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

IMPORTANCE Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking. OBJECTIVE To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden. DESIGN, SETTING, AND PATIENTS Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. EXPOSURES In-hospital treatment with fondaparinux or LMWH during the hospital stay. MAIN OUTCOMES AND MEASURES In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization. RESULTS In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups. CONCLUSIONS AND RELEVANCE In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction

BACKGROUND There is no consensus whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) should be used for secondary prevention in all or in only high-risk patients after an acute myocardial infarction (AMI). OBJECTIVES This study sought to investigate whether ACEI/ARB treatment after AMI is associated with better outcomes across different risk profiles, including the entire spectrum of estimated glomerular filtration rates. METHODS This study evaluated discharge and continuous follow-up data on ACEI/ARB use among AMI survivors (2006 to 2009) included in a large Swedish registry. The association between ACEI/ARB treatment and outcomes (mortality, myocardial infarction, stroke, and acute kidney injury [AKI]) was studied using Cox proportional hazards models (intention-to-treat and as treated). RESULTS In total, 45,697 patients (71%) were treated with ACEI/ARB. The 3-year mortality was 19.8% (17.4% of ACEI/ARB users and 25.4% of nonusers). In adjusted analysis, significantly better survival was observed for patients treated with ACEI/ARB (3-year hazard ratio: 0.80; 95% confidence interval: 0.77 to 0.83). The survival benefit was consistent through all kidney function strata, including dialysis patients. Overall, those treated with ACEI/ARB also had lower 3-year risk for myocardial infarction (hazard ratio: 0.91; 95% confidence interval: 0.87 to 0.95), whereas treatment had no significant effect on stroke risk. The crude risk for AKI was in general low (2.5% and 2.0% for treated and nontreated, respectively) and similar across estimated glomerular filtration rate categories but was significantly higher with ACEI/ARB treatment. However, the composite outcome of AKI and mortality favored ACEI/ARB treatment. CONCLUSIONS Treatment with ACEI/ARB after AMI was associated with improved long-term survival, regardless of underlying renal function, and was accompanied by low rates of adverse renal events.

Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial infarction stratified by renal function

Objectives We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI). Methods We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1 year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels. Results In total, 45 206 patients with MI discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR>60 (n=33 668), eGFR30–60 (n=9803) and eGFR<30 (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR>60: HR 0.87, 95% CI 0.76 to 99, eGFR30–60: 0.82 (0.70 to 0.97), eGFR<30: 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR>60: HR 1.10, 95% CI 0.90 to 1.35, eGFR30–60: 1.13 (0.84 to 1.51), eGFR<30: 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata. Conclusions Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR<30.

Renal function is associated with long-term outcomes independent of degree of atherosclerosis: 6-year data from the Swedish Coronary Angiography and Angioplasty Registry

Aims To study the association between renal function and outcomes in a nationwide cohort of unselected consecutive patients with stable coronary artery disease (SCAD) symptoms and with a defined coronary anatomy by a coronary angiogram (CA). Methods and results We included 45 348 consecutive patients with available plasma creatinine undergoing CA for suspected SCAD from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We adjusted for clinical background, severity of CAD and subsequent revascularization in a Cox regression analysis. Patients were followed for a median (interquartile range) time of 2.6 (1.2-4.1) years. The 3-year cumulative probability of death, myocardial infarction (MI), heart failure, and stroke increased from 2.7, 4.6, 4.4, and 2.0% in patients with estimated glomerular function (eGFR) >90 to 39.8, 32.8, 30.2, and 6.2% in patients with eGFR <15. Compared with patients with eGFR > 90 mL/min/m2, patients with impaired renal function (eGFR 30-59, 15-29, and <15 mL/min/m2) had significantly higher risk of death (HR (95%CI): 1.3 (1.1-1.5), 2.2 (1.6-2.9), 7.7 (6.1-9.8)), MI (1.3 (1.1-1.5), 1.8 (1.4-2.5), 4.0 (3.1-5.1)), and heart failure (1.7 (1.5-1.9), 2.5 (1.9-3.1), 2.4 (1.8-3.2)), but not of stroke (1.1 (0.9-1.3), 1.1 (0.6-1.7), 1.4 (0.7-2.5)) after multivariable adjustment. For patients with eGFR 60-89, there was no significant difference in the risk of death, MI or stroke but increased risk of heart failure 1.2 (1.1-1.3). Conclusion Impaired renal function is strongly associated with worse outcome in patients with SCAD and known coronary anatomy. The associations were independent of traditional cardio vascular disease risk factors, comorbidities, coronary artery obstruction severity, and subsequent revascularization.

IMPROVING SURVIVIAL IN MYOCARDIAL INFARCTION PATIENTS WITH RENAL DYSFUNCTION: TEMPORAL TRENDS IN THE SWEDEHEART REGISTRY FROM 2003 TO 2010

Survival after myocardial infarction (MI) has improved markedly during the last decade. It is still unknown whether this improvement in survival also confers to MI patients with renal impairment. We used the SWEDEHEART registry covering all emergency hospitals in Sweden. All MI cases with available