Inequality in oral anticoagulation use and clinical outcomes in atrial fibrillation: a Danish nationwide perspective.

Aim: To explore the potential of small-area variation analysis as a tool for identifying unwarranted variation in oral anticoagulation (OAC) use and clinical outcomes in patients with atrial fibrillation (AF) and thereby identify locations with opportunity for improvement in AF care. Methods and results: Based on Danish health care registries, we conducted a nationwide historical cohort study including first-time AF patients with a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75, diabetes, thromboembolism, vascular disease, age 65-74, and sex category) score ≥ 2 between 2007 and 2014 (n = 94 482). For each administrative region and municipality, we assessed OAC initiation and persistence as well as the risk of ischaemic stroke, haemorrhagic stroke, and other major bleeding, respectively. In addition, potential temporal changes were examined for all outcomes. Initiation of OAC varied among regions from 49.5% to 62.4%. In patients initiating OAC, the proportion of patients still receiving OAC after 1 year varied from 73.9% to 79.3%. Oral anticoagulation use increased in all regions during the study period, particularly after 2010, but regional variation in OAC initiation persisted. Generally, the regions and municipalities with the highest initiation of OAC also had the highest OAC persistence. The risk of ischaemic stroke and other major bleeding was lower in these regions and municipalities. We found no significant difference between regions in risk of haemorrhagic stroke. Conclusion: Substantial geographical variation in OAC use and clinical outcomes occurs in Denmark demonstrating the potential of small-area variation analysis as a tool for identifying unwarranted variation in AF care and clinical outcomes. Our findings demonstrate the need for additional initiatives to ensure uniform high-quality care for AF patients.

Single lead atrial vs. dual chamber pacing in sick sinus syndrome: extended register-based follow-up in the DANPACE trial.

AIMS: The DANPACE trial randomized patients with sick sinus syndrome (SSS) to single lead atrial (AAIR) or dual chamber (DDDR) pacemaker (PM). After 5 years follow-up, no difference in overall survival, stroke or heart failure (HF) was observed, whereas risk of atrial fibrillation (AF) and PM reoperation were increased in the AAIR group. The present study aimed to investigate very long term risk of death, AF hospitalization, stroke, HF and rate of change in pacing mode using national register-based data. METHODS AND RESULTS: The study population consisted of all 1384 patients included at Danish PM centres in the DANPACE trial randomized to AAIR (n = 696) or DDDR (n = 688). Long-term follow-up data was obtained from Danish national registers. Analysis was intention-to-treat. results: During mean follow-up of 8.9 years, 413 patients (59.3%) died in the AAIR-group compared to 367 (53.3%) in the DDDR-group (adjusted hazard ratio 1.03; 95% confidence interval 0.90-1.19; P = 0.65). We observed no difference in risk of AF hospitalization, stroke or HF. During extended follow-up, annual rate of pacing mode change to DDDR in the AAIR group was 4.5%, and higher than the 2.3% observed during trial conduct. CONCLUSION: This register-based long-term follow-up study indicates that there is no difference in mortality among patients with SSS randomized to AAIR or DDDR pacing, even with very long follow-up. Nor is there any difference in risk of AF hospitalization, stroke or HF. The higher rate of pacing mode-change to DDDR in the AAIR group suggests a different management of patients with an AAIR PM after the DANPACE trial.

Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial.

OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up. METHODS: This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data. RESULTS: 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, χ2 test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores. CONCLUSIONS: At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences. TRIAL REGISTRATION NUMBER: NCT00133211; Results.

Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population.

OBJECTIVE: A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death. METHODS: All patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts. RESULTS: A total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23). CONCLUSIONS: Structured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings.

Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation: On-treatment analysis of the randomized controlled MANTRA-PAF trial.

BACKGROUND: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data. METHODS AND RESULTS: Patients (n=294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24 months and cumulative AF burden in all recordings. At 24 months, AF burden was significantly lower in the RFA (n=110) than in the AAD (n=92) and the crossover (n=84) groups (90th percentile 1% vs. 10% vs. 16%, P=0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P=0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (P<0.001) of the patients had no AF episodes in any Holter recording, respectively. Quality of life improved significantly in all groups. There were no differences in serious adverse events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10). CONCLUSIONS: In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s).

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.

AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

CHADS2 and CHA2DS2-VASc score to assess risk of stroke and death in patients paced for sick sinus syndrome.

OBJECTIVE: The risk of stroke in patients with atrial fibrillation (AF) can be assessed by use of the CHADS2 and the CHA2DS2-VASc score system. We hypothesised that these risk scores and their individual components could also be applied to patients paced for sick sinus syndrome (SSS) to evaluate risk of stroke and death. DESIGN: Prospective cohort study. SETTINGS: All Danish pacemaker centres and selected centres in the UK and Canada. PATIENTS: Risk factors were recorded prior to pacemaker implantation in 1415 patients with SSS participating in the Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber Pacing in Sick Sinus Syndrome (Danpace) trial. Development of stroke was assessed at follow-up visits and by evaluation of patient charts. Mortality was assessed from the civil registration system. INTERVENTIONS: Patients were randomised to AAIR (N = 707) or DDDR pacing (N = 708). MAIN OUTCOME MEASURES: Stroke and death during follow-up. RESULTS: Mean follow-up was 4.3 ± 2.5 years. In the AAIR group 6.9% patients developed stroke versus 6.1% in the DDDR group (NS). There was a significant association between CHADS2 score and the development of stroke (HR 1.41; 95% CI 1.22 to 1.64, p < 0.001). CHA2DS2-VASc score was also significantly associated with stroke (HR 1.25; CI 1.12 to 1.40, p < 0.001). CHADS2 score (HR 1.46; CI 1.36 to 1.56, p < 0.001) and CHA2DS2-VASc score (HR 1.39; CI 1.31 to 1.46, p < 0.001) were associated with mortality. Results were still significant after adjusting for AF and anticoagulation therapy. CONCLUSIONS: CHADS2 and CHA2DS2-VASc score are associated with increased risk of stroke and death in patients paced for SSS irrespective of the presence of AF.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

Uraemia progression in chronic kidney disease stages 3-5 is not constant.

INTRODUCTION: Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m(2)/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating. METHODS: 1,441 patients attending a nephrology clinic over a 21-year period, with an initial eGFR <60 ml/min/1.73 m(2) and an observation period ≥2 years, were included. eGFR was calculated from all creatinine measurements. 420 patients developed end-stage renal disease (ESRD). First- and second-order polynomial regression analysis of eGFR against time was performed for each patient individually. Patients had accelerating uraemia progression if the second-order term coefficient was negative. RESULTS: The initial eGFR was 30.8 ±15.1 ml/min/1.73 m(2). The second-order coefficient was median -0.15 ml/min/1.73 m(2)/year(2) (interquartile range -0.92, +0.34). Significantly more patients had an accelerating loss (62%, p < 0.001). Acceleration was mainly seen when eGFR was <30 ml/min. ΔGFR was mean 1.47 ± 4.5 ml/min/1.73 m(2)/year (male 1.67, female 1.22). ESRD patients lost 5.4 ± 5.4 ml/min/year/1.73 m(2) during the last year before ESRD. Accelerating loss was seen for all diagnoses except polycystic disease. Diagnoses with higher ΔGFR were polycystic renal disease (3.3 ml/min/1.73 m(2)/year), hypertensive nephropathy (2.1 ml/min/1.73 m(2)/year) and diabetic nephropathy (2.6 ml/min/ 1.73 m(2)/year). There was no evidence of improvement in overall uraemia progression during the period of observation. CONCLUSIONS: Uraemia progression in CKD stages 3-5 is not linear, but shows an accelerating trend. This suggests that hyperfiltration mechanisms play a role in CKD progression. ESRD cannot thus be predicted from previous ΔGFR alone.

Time to treatment and three-year mortality after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction-a DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) substudy.

In patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI), early reperfusion is believed to improve left ventricular systolic function and reduce mortality; however, long-term (>1 year) data are sparse. In the DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) study, 686 patients with ST-segment elevation myocardial infarction were treated with pPCI. Long-term mortality was obtained during 3 years of follow-up. We classified the patients according to the symptom-to-balloon time (<3, 3 to 5, and > or =5 hours). The groups were compared using a Cox proportional hazards regression model adjusted for confounding factors. The left ventricular systolic ejection fraction was estimated by echocardiography before discharge. Coronary flow was evaluated using the Thrombolysis In Myocardial Infarction score. Mortality did not differ between the 2 earliest symptom-to-balloon groups, and they were therefore combined into 1 group in the analysis of survival. Mortality was significantly increased for patients with a symptom-to-balloon time > or =5 hours (hazard ratio 2.36, 95% confidence interval 1.51 to 3.67, p <0.001), a difference that remained significant after controlling for confounding factors (adjusted hazard ratio 2.44, 95% confidence interval 1.31 to 4.54, p = 0.007). The symptom-to-balloon time was inversely associated with a left ventricular systolic ejection fraction of < or =40% (19.7% vs 22.8% vs 33.1%, p = 0.036), with the latter a major predictor of 3-year mortality in this cohort (hazard ratio 6.02, 95% confidence interval 3.68 to 9.85, p <0.001). A shorter symptom-to-balloon time was associated with greater rates of Thrombolysis In Myocardial Infarction 3 flow after pPCI (86.5% vs 80.9% vs 75.7%, p = 0.002). In conclusion, a shorter symptom-to-balloon time was associated with improved coronary flow, an increased likelihood of subsequent left ventricular systolic ejection fraction >40%, and greater 3-year survival in patients with ST-segment elevation myocardial infarction treated with pPCI.

The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial: clinical rationale, study design, and implementation.

AIMS: No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION: The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

Long-term outcome of primary angioplasty compared with fibrinolysis across age groups: a Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) substudy.

BACKGROUND: Primary angioplasty in patients with acute ST-elevation myocardial infarction has been shown to be superior to fibrinolysis. Whether elderly patients have the same long-term benefit from angioplasty, compared with fibrinolysis, as younger patients is unknown. METHODS: The effect of angioplasty versus fibrinolysis was investigated in 1,572 patients from the DANAMI-2 study across age groups. End points were total mortality and a composite end point of death, reinfarction, or disabling stroke. Follow-up was 3 years. RESULTS: Increasing age was associated with mortality (adjusted hazard ratio [HR] 2.45 per 10 year increment, 95% confidence interval [CI] 1.78-3.37, P < .0001) and a higher composite event rate (adjusted HR 1.51, CI 1.26-1.82, P < .0001). The long-term superiority of angioplasty over fibrinolysis on the combined outcome was independent of age: patients aged <56 years (HR 0.73, CI 0.41-1.31); 56 to 65 years (HR 0.83, CI 0.52-1.33); 66 to 75 years (HR 0.71, CI 0.48-1.04); and >75 years (HR 0.83, CI 0.59-1.17) (P = .006 for overall treatment effect and P = .5 for interaction between age and treatment). There was no long-term effect of angioplasty versus fibrinolysis on mortality and no interaction with age (P = .5 and P for interaction = .6). CONCLUSIONS: The long-term effect of primary angioplasty compared with fibrinolysis in patients with ST-elevation myocardial infarction is not affected by age.

Lost life years attributable to stroke among patients with nonvalvular atrial fibrillation: a nationwide population-based follow-up study.

AIM: We assessed the number of lost life years attributable to stroke among patients with a hospital diagnosis of nonvalvular atrial fibrillation. METHODS: We identified all patients, aged 40-89 years, with an incident hospital diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients from calendar year 1980 to 2002, and no previous or concomitant diagnosis of stroke or heart valve disease. All patients were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any type (ischemic and/or hemorrhagic) and in the Danish Civil Registration System for emigration or change in vital status. We used multivariate Cox regression analysis with stroke as a time dependent covariate to estimate excess mortality associated with incident stroke. The baseline hazard function for mortality was computed and used for modeling lost life years by sex, age, and time to incident stroke after diagnosis of atrial fibrillation, adjusted for conditions of comorbidity and calendar year of diagnosis of atrial fibrillation. RESULTS: The mean loss of life years attributable to incident stroke within 20 years after a first diagnosis of atrial fibrillation was most frequently less than 5 years, but a mean of up to 10 years of lost life years was observed. The largest number of lost life years was observed in women, in younger patients, and in those who had a stroke early after the diagnosis of atrial fibrillation. The relative loss of life years was up to 90% of the estimated expected remaining lifetime without stroke within 20 years after the diagnosis of atrial fibrillation, and was highest in the elderly. CONCLUSION: Stroke causes a substantial loss of life years in patients with atrial fibrillation.

Age and risk of stroke in atrial fibrillation: evidence for guidelines?

AIM: Guidelines for the clinical management of patients with atrial fibrillation suggest that treatment strategies for prescribing oral anticoagulant therapy should implicate change at age 60, 65 and 75 years. We examined if there is any threshold concerning risk of stroke by age. METHODS: We identified 141,493 subjects, aged 40-89 years, with an incident hospital diagnosis of nonvalvular atrial fibrillation or flutter and no previous or concomitant diagnosis of stroke in the Danish National Registry of Patients from January 1, 1980, to December 31, 2002. The subjects were followed in the Danish National Registry of Patients for the occurrence of an incident diagnosis of stroke of any nature and in the Danish Civil Registration System for emigration and vital status. We examined the risk of stroke by age in men and women using Cox regression models, which included age categorized in intervals, linear splines of age with cut points at age 60 and 75 years, or at age 65 and 75 years. We also analyzed age as a continuous variable in linear and polynomial regression models. RESULTS: During follow-up 15,964 incident strokes were reported to the Danish National Registry of Patients. The risk of stroke increased by increasing age at baseline. We did not find any evidence for a threshold concerning risk of stroke by age, and the best model fit was obtained in a third-order polynomial regression model. CONCLUSION: The risk of stroke increased gradually by increasing age, and we could not detect any threshold concerning risk of stroke by age.

Trend in mortality after stroke with atrial fibrillation.

PURPOSE: To evaluate trend in mortality in stroke associated with atrial fibrillation, we examined mortality trend after stroke with atrial fibrillation by calendar year period (1980-1984, 1985-1989, 1990-1994, 1995-1999, and 2000-2002). We estimated trends separately for each sex in unadjusted analyses. We also adjusted for age, comorbid conditions, and general trend in mortality in the background population. METHODS: We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used multivariate Cox proportional hazards regression analysis to estimate trend in mortality. RESULTS: Incident stroke with a previous or concomitant diagnosis of nonvalvular atrial fibrillation or flutter was diagnosed in 24,470 subjects (11,554 men and 12,916 women). During 34,405 years of observation, 9237 men died, and during 35,381 years of observation, 10,827 women died. The hazard ratio for mortality after stroke in the last 3-year period compared with the first 5-year period was .65 (95% confidence interval [CI], .61-.71) in men and .69 (95% CI, .64-.74) in women. CONCLUSIONS: We observed a substantially better survival in men and women after stroke associated with atrial fibrillation or flutter in Denmark during the years 1980 to 2002. However, we could not control for changes in admission practice, diagnostic performance, or treatment.

Trends in risk of stroke in patients with a hospital diagnosis of nonvalvular atrial fibrillation: National Cohort Study in Denmark, 1980-2002.

AIM: We examined trends in incidence of stroke of any nature (ischemic and/or hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions of comorbidity. METHODS: We identified all individuals, aged 40-89 years, with an incident hospital diagnosis of atrial fibrillation or flutter and no history of stroke or heart valve disease in the Danish National Registry of Patients, and subjects were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic) and in the Danish Civil Registration System (emigration and vital status). We used multivariate Cox proportional hazard regression analysis to estimate trends in incidence of stroke. RESULTS: Nonvalvular atrial fibrillation or flutter was diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up 15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke in the last 3-year period compared to the first 5-year period, adjusted for 10-year age group, conditions of comorbidity, and general stroke trend in the Danish population were 0.78 (95% CI 0.70-0.86) in men, and 0.80 (95% CI 0.72-0.88) in women. The reduction in risk of stroke by calendar year was most prominent in patients aged 40-74 years. CONCLUSION: We observed a modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980-2002. However, we could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrial fibrillation.

Seasonal variation in stroke and stroke-associated mortality in patients with a hospital diagnosis of nonvalvular atrial fibrillation or flutter. A population-based study in Denmark.

AIM: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. METHODS: We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980-2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. RESULTS: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07-1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. CONCLUSIONS: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.

Usefulness of quantitative baseline ST-segment elevation for predicting outcomes after primary coronary angioplasty or fibrinolysis (results from the DANAMI-2 trial).

The DANAMI-2 trial showed a 40% decrease in the composite end point with primary coronary angioplasty versus fibrinolysis. This result was primarily driven by a decrease in reinfarction, with no significant difference in mortality or stroke rates. The objective of this study was to determine the prognostic value of the sum ST-segment elevation (SigmaST) on baseline electrocardiography in patients who were randomized to receive primary coronary angioplasty versus fibrinolysis. In the DANAMI-2, 1,450 patients had baseline ST-segment deviation measurements and were assigned to quartiles according to SigmaST: 0 to 6.5, 7.0 to 9.5, 10.0 to 14.5, and 15.0 to 70.5 mm. The composite and component end-point rates at 30 days were determined for each quartile and chi-square for trend statistic was used to compare end-point rates across quartiles of SigmaST. The composite end point occurred more often with increasing SigmaST (p = 0.05). With regard to component end points, only mortality increased significantly with SigmaST (p = 0.03), whereas reinfarction and stroke rates did not. By multivariate analysis, only SigmaST and age were independent predictors of mortality. The relative benefit of primary coronary angioplasty was similar for all SigmaST quartiles. In conclusion, the magnitude of SigmaST correlates with increased mortality at 30 days, thus driving the composite end point rate. Regardless of SigmaST, patients had a lower composite end-point rate with primary coronary angioplasty than with fibrinolysis.

Coronary artery bypass grafting within the first year after treatment of large acute myocardial infarctions with angioplasty or fibrinolysis.

OBJECTIVES: To calculate the incidence and analyse and outcome after coronary artery bypass grafting (CABG) within the first year after randomisation of 1,572 patients with acute myocardial infarctions with ST-segment elevation (STEMI) to either percutaneous coronary intervention (PCI) or fibrinolysis. DESIGN: The study includes 131 patients: 108 male and 23 female with a mean age 62 years. RESULTS: The total 30-day mortality after CABG was 4.6% (7.5% in the PCI group and 2.6% in the fibrinolysis group). The 30-day mortality was 9.8% after CABG within the first 30-days and 1.3% after CABG within 31-365 days. The patients who were operated early had a reduced EF to 43% as compared to 50% in patients who were not operated or patients having CABG after 30-days (p=0.002). CONCLUSION: CABG was performed within the first year after STEMI in 10% of patients randomised to fibrinolysis and in 6.7% of patients randomised to PCI. Patients having CABG within the first 30-days after treatment of STEMI had an increased mortality of 9.8%.