Jonas Bjerring Olesen

Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study.

Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. Design Registry based cohort study. Setting Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. Main outcome measures Stroke and thromboembolism. Results Of 121 280 patients with non-valvular atrial fibrillation, 73 538 (60.6%) fulfilled the study inclusion criteria. In patients at “low risk” (score=0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS2 and 0.78 (0.58 to 1.04) with CHA2DS2-VASc at one year’s follow-up. In patients at “intermediate risk” (score=1), this rate was 4.75 (4.45 to 5.07) with CHADS2 and 2.01 (1.70 to 2.36) with CHA2DS2-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years’ follow-up were 0.812 (0.796 to 0.827) with CHADS2 and 0.888 (0.875 to 0.900) with CHA2DS2-VASc. Conclusions The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA2DS2-VASc performed better than CHADS2 in predicting patients at high risk, and those categorised as low risk by CHA2DS2-VASc were truly at low risk for thromboembolism.

Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

BACKGROUND Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. METHODS Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. RESULTS Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. CONCLUSIONS Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest

IMPORTANCE Out-of-hospital cardiac arrest is a major health problem associated with poor outcomes. Early recognition and intervention are critical for patient survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many associated with improved survival. OBJECTIVE To examine temporal changes in bystander resuscitation attempts and survival during a 10-year period in which several national initiatives were taken to increase rates of bystander resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS Patients with out-of-hospital cardiac arrest for which resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29,111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n = 2253), leaving a study population of 19,468 patients. MAIN OUTCOMES AND MEASURES Temporal trends in bystander CPR, bystander defibrillation, 30-day survival, and 1-year survival. RESULTS The median age of patients was 72 years; 67.4% were men. Bystander CPR increased significantly during the study period, from 21.1% (95% CI, 18.8%-23.4%) in 2001 to 44.9% (95% CI, 42.6%-47.1%) in 2010 (P < .001), whereas use of defibrillation by bystanders remained low (1.1% [95% CI, 0.6%-1.9%] in 2001 to 2.2% [95% CI, 1.5%-2.9%] in 2010; P = .003). More patients achieved survival on hospital arrival (7.9% [95% CI, 6.4%-9.5%] in 2001 to 21.8% [95% CI, 19.8%-23.8%] in 2010; P < .001). Also, 30-day survival improved (3.5% [95% CI, 2.5%-4.5%] in 2001 to 10.8% [95% CI, 9.4%-12.2%] in 2010; P < .001), as did 1-year survival (2.9% [95% CI, 2.0%-3.9%] in 2001 to 10.2% [95% CI, 8.9%-11.6%] in 2010; P < .001). Despite a decrease in the incidence of out-of-hospital cardiac arrests during the study period (40.4 to 34.4 per 100,000 persons in 2001 and 2010, respectively; P = .002), the number of survivors per 100,000 persons increased significantly (P < .001). For the entire study period, bystander CPR was positively associated with 30-day survival, regardless of witnessed status (30-day survival for nonwitnessed cardiac arrest, 4.3% [95% CI, 3.4%-5.2%] with bystander CPR and 1.0% [95% CI, 0.8%-1.3%] without; odds ratio, 4.38 [95% CI, 3.17-6.06]). For witnessed arrest the corresponding values were 19.4% (95% CI, 18.1%-20.7%) vs 6.1% (95% CI, 5.4%-6.7%); odds ratio, 3.74 (95% CI, 3.26-4.28). CONCLUSIONS AND RELEVANCE In Denmark between 2001 and 2010, an increase in survival following out-of-hospital cardiac arrest was significantly associated with a concomitant increase in bystander CPR. Because of the co-occurrence of other related initiatives, a causal relationship remains uncertain.

Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study

It was the aim of this study to determine the efficacy and safety of vitamin K antagonists (VKAs) and acetylsalicylic acid (ASA) in patients with non-valvular atrial fibrillation (AF), with separate analyses according to predicted thromboembolic and bleeding risk. By individual level-linkage of nationwide registries, we identified all patients discharged with non-valvular AF in Denmark (n=132,372). For every patient, the risk of stroke and bleeding was calculated by CHADS₂, CHA₂DS₂-VASc, and HAS-BLED. During follow-up, treatment with VKA and ASA was determined time-dependently. VKA consistently lowered the risk of thromboembolism compared to ASA and no treatment; the combination of VKA+ASA did not yield any additional benefit. In patients at high thromboembolic risk, hazard ratios (95% confidence interval) for thromboembolism were: 1.81 (1.73-1.90), 1.14 (1.06-1.23), and 1.86 (1.78-1.95) for ASA, VKA+ASA, and no treatment, respectively, compared to VKA. The risk of bleeding was increased with VKA, ASA, and VKA+ASA compared to no treatment, the hazard ratios were: 1.0 (VKA; reference), 0.93 (ASA; 0.89-0.97), 1.64 (VKA+ASA; 1.55-1.74), and 0.84 (no treatment; 0.81-0.88), respectively. There was a neutral or positive net clinical benefit (ischaemic stroke vs. intracranial haemorrhage) with VKA alone in patients with a CHADS₂ score of ≥ 0, and CHA₂DS₂-VASc score of ≥ 1. This large cohort study confirms the efficacy of VKA and no effect of ASA treatment on the risk of stroke/thromboembolism. Also, the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was clearly positive, in favour of VKA in patients with increased risk of stroke/thromboembolism.

Bleeding after Initiation of Multiple Antithrombotic Drugs, Including Triple Therapy, in Atrial Fibrillation Patients Following Myocardial Infarction and Coronary Intervention: A Nationwide Cohort Study

Background— Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment. Methods and Results— Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90–360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40). Conclusions— High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.

Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study

Abstract.  Ahlehoff O, Gislason GH, Charlot M, Jørgensen CH, Lindhardsen J, Olesen JB, Abildstrøm SZ, Skov L, Torp‐Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen University Hospital Bispebjerg, Copenhagen; National Institute of Public Health, University of Southern Denmark, Copenhagen; Copenhagen University Hospital Gentofte, Hellerup; University of Copenhagen, Copenhagen, Denmark) Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med2011; 270: 147–157.

Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction A Nationwide Cohort Study

Background— Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI). Methods and Results— Patients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment). Conclusions— Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention.

OBJECTIVES The purpose of this study was to investigate the risk of thrombosis and bleeding according to multiple antithrombotic treatment regimens in atrial fibrillation (AF) patients after myocardial infarction (MI) or percutaneous coronary intervention (PCI). BACKGROUND The optimal antithrombotic treatment strategy is unresolved in patients with multiple indications. METHODS A total of 12,165 AF patients hospitalized with MI and/or undergoing PCI between 2001 and 2009 were identified by nationwide registries (60.7% male; mean age 75.6 years). Risk of MI/coronary death, ischemic stroke, and bleeding according to antithrombotic treatment regimen was estimated by Cox regression models. RESULTS Within 1 year, MI or coronary death, ischemic stroke, and bleeding events occurred in 2,255 patients (18.5%), 680 (5.6%), and 769 (6.3%), respectively. Relative to triple therapy (oral anticoagulation [OAC] plus aspirin plus clopidogrel), no increased risk of recurrent coronary events was seen for OAC plus clopidogrel (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.48 to 1.00), OAC plus aspirin (HR: 0.96, 95% CI: 0.77 to 1.19), or aspirin plus clopidogrel (HR: 1.17, 95% CI: 0.96 to 1.42), but aspirin plus clopidogrel was associated with a higher risk of ischemic stroke (HR: 1.50, 95% CI: 1.03 to 2.20). Also, OAC plus aspirin and aspirin plus clopidogrel were associated with a significant increased risk of all-cause death (HR: 1.52, 95% CI: 1.17 to 1.99 and HR: 1.60, 95% CI: 1.25 to 2.05, respectively). When compared to triple therapy, bleeding risk was nonsignificantly lower for OAC plus clopidogrel (HR: 0.78, 95% CI: 0.55 to 1.12) and significantly lower for OAC plus aspirin and aspirin plus clopidogrel. CONCLUSIONS In real-life AF patients with indication for multiple antithrombotic drugs after MI/PCI, OAC and clopidogrel was equal or better on both benefit and safety outcomes compared to triple therapy.

The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study

Objectives To examine in a nationwide cohort whether the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) is comparable to the risk in patients with diabetes mellitus (DM). Methods The study included the entire Danish population followed from 1 January 1997 until 31 December 2006. Through individual level-linkage of nationwide administrative registers, the authors identified subjects who developed RA and DM. The risk of MI was analysed using multivariable Poisson regression models including data on cardioprotective drugs, comorbidity and socioeconomic status. Results From a total of 4 311 022 individuals included in the cohort, 10 477 and 130 215 individuals developed RA and DM respectively. The overall incidence rate ratio (IRR) of MI in RA was 1.7 (95% CI 1.5 to 1.9), which was similar to the risk in DM (1.7 (1.6 to 1.8); p=0.64 for difference). The risk was significantly increased in all groups when stratifying on age and gender, with higher RRs in younger patients. This was especially pronounced in women <50 years with RA or DM, who were subject to a sixfold increase in RR. The RA-related risk of MI was unaffected by the duration of pharmacological RA treatment and corresponded to the overall risk of MI observed in non-RA subjects, who were on the average 10 years older. Conclusions RA is associated with the same risk of MI as DM, and the risk of MI in RA patients generally corresponded to the risk in non-RA subjects 10 years older.

Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort

Summary.  Background: Oral anticoagulation (OAC) in patients with atrial fibrillation (AF) is a double‐edged sword, because it decreases the risk of stroke at the cost of an increased risk of bleeding. We compared the performance of a new bleeding prediction scheme, HAS‐BLED, with an older bleeding prediction scheme, HEMORR2HAGES, in a cohort of ‘real‐world’ AF patients. Methods: By individual‐level‐linkage of nationwide registers, we identified all patients (n = 118 584) discharged with non‐valvular AF in Denmark during the period 1997–2006, with and without OAC. Major bleeding rates during 1 year of follow‐up were determined, and the predictive capabilities of the two schemes were compared by c‐statistics. The risk of bleeding associated with individual risk factors composing HAS‐BLED was estimated using Cox proportional‐hazard analyses. Results: Of AF patients receiving OAC (n = 44 771), 34.8% and 47.3% were categorized as ‘low bleeding risk’ by HAS‐BLED and HEMORR2HAGES, respectively, and the bleeding rates per 100 person‐years were 2.66 (95% confidence interval [CI], 2.40–2.94) and 3.06 (2.83–3.32), respectively. C‐statistics for the two schemes were 0.795 (0.759–0.829) and 0.771 (0.733–0.806), respectively. The risk factors composing HAS‐BLED were associated with varying risks, with a history of bleeding (hazard ratio [HR] 2.98; 95% CI 2.68–3.31) and being elderly (HR 1.93; 95% CI 1.71–2.18) being associated with the highest risks. Comparable results were found in AF patients not receiving OAC (n = 77 813). Conclusions: In an unselected nationwide cohort of hospitalized patients with atrial fibrillation, the HAS‐BLED score performs similarly to HEMORR2HAGES in predicting bleeding risk but HAS‐BLED is much simpler and easier to use in everyday clinical practise.