Jens Friberg

Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction.

Background— The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI. Methods and Results— All patients with first-time MI between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from nationwide Danish administrative registers. The risk of death and rehospitalization for MI associated with the use of selective COX-2 inhibitors and nonselective NSAIDs was studied with the use of multivariable proportional hazards models and case-crossover analysis. A total of 58 432 patients were discharged alive and included in the study; 9773 experienced rehospitalization for MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; for other NSAIDS); there were dose-related increases in risk of death for all of the drugs. There were trends for increased risk of rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs. Conclusions— Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients.

Rising rates of hospital admissions for atrial fibrillation.

Background: Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study). Methods: The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years. We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods. Changes in admission rates were analyzed using Cox proportional hazard models. Results: During the 2 7-year periods, 379 subjects were admitted with a hospital diagnosis of atrial fibrillation. The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period (relative risk = 1.6; 95% confidence interval = 1.3–1.9 [adjusted for age, sex, prior myocardial infarction, arterial hypertension, diabetes mellitus, electrocardiographic left ventricular hypertrophy, decreased lung function, smoking, height, and weight]). Conclusion: During the latest 10 to 20 years, there has been a 60% increase in hospital admissions for atrial fibrillation independent of changes in known risk factors. This increase could result from changes in admission threshold or coding practices, or it could reflect a genuine increase in the population incidence of atrial fibrillation.

Alcohol Consumption and Risk of Atrial Fibrillation in Men and Women The Copenhagen City Heart Study

Background—The relationship of the full range of alcohol consumption with risk of incident atrial fibrillation has been inconsistent in previous, mainly case-control studies. Methods and Results—In a prospective cohort study, we studied the association between self-reported alcohol use and incident atrial fibrillation among 16 415 women and men enrolled in the Copenhagen City Heart Study. We ascertained use of beer, wine, and spirits individually at up to 3 study visits with a structured questionnaire. We identified cases of atrial fibrillation by routine study ECGs and a validated nationwide registry of all hospitalizations. A total of 1071 cases occurred during follow-up. Among both women and men, alcohol consumption throughout the moderate range was not associated with risk of atrial fibrillation. However, consumption of 35 or more drinks per week among men was associated with a hazard ratio of 1.45 (95% CI 1.02 to 2.04); few women consumed this amount of alcohol. Approximately 5% of cases of atrial fibrillation among men were attributable to heavy alcohol use. Further adjustment for blood pressure and incident coronary heart disease and congestive heart failure did not attenuate the association (hazard ratio 1.63; 95% CI 1.15 to 2.31). Conclusions—Heavy alcohol consumption is associated with a higher risk of atrial fibrillation, at least among men. This relationship does not appear to be related to the adverse effects of heavy drinking on coronary heart disease or blood pressure.

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995–2002

Objectives To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. Design Information about patients with first AMI aged ≥30 years and the dispensing of beta-blockers and ACE inhibitors from pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. Results Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR=3.85, CI: 3.58–4.13). Women, elderly patients and patients taking loop-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR=1.86, CI: 1.72–2.01). Women, patients aged <60 years or ≥80 years and patients not taking loop-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. Conclusions Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people with diabetes.

Atrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers.

AIMS To study evolvement in pharmacotherapy of atrial fibrillation from 1995 to 2004. METHODS AND RESULTS All Danish patients were discharged following first-time atrial fibrillation and their pharmacotherapy was identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. A total of 108 791 patients survived 30 days after discharge and were included. In 1995-1996, 7.4% of the patients received beta-blockers, increasing to 44.3% in 2003-2004. The corresponding figures for amiodarone were 2.9 and 5.4%. In contrast, use of nondihydropyridine calcium-channel blockers, digoxin, sotalol, and class 1C antiarrhythmics decreased from 20.6, 63.9, 21.3, and 4.0% in 1995-1996 to 12.6, 43.8, 4.2, and 1.3% in 2003-2004, respectively. Notably, patients receiving anticoagulants increased from 29.8 to 43.5%. Multivariate logistic regression analysis revealed females to be associated with more use of digoxin, but less use of amiodarone and oral anticoagulants than males. Patients above 80 years received less pharmacotherapy, apart from digoxin treatment that was more commonly used in elderly. CONCLUSION Pharmacotherapy of atrial fibrillation has changed towards increased beta-blocker use with a coincident decrease in the use of other rate-limiting drugs and sotalol. Treatment with amiodarone or class 1C antiarrhythmics remained very low. Oral anticoagulant therapy increased considerably, but women and elderly were apparently undertreated.

Flow‐mediated dilatation has no independent prognostic effect in patients with chest pain with or without ischaemic heart disease

Objective: The purpose of this study was to assess the prognostic effect of flow‐mediated dilatation (FMD) in patients with chest pain admitted to a coronary care unit. Methods: Endothelium‐dependent FMD in the brachial artery was examined in 223 patients with acute chest pain. All patients underwent a stress test at the time of admittance. On the basis of a positive stress test, a prior myocardial infarction (MI), prior percutaneous coronary intervention (PCI) or coronary bypass surgery (CABG), 137 patients were categorized as having ischaemic heart disease (IHD). Results: Patients with IHD had significantly lower FMD than patients without IHD (p=0.002). During a mean follow‐up of 4.2 years, 90 patients had an endpoint event, i.e. cardiovascular death, acute MI, unstable angina pectoris, PCI or CABG. In univariate analysis, FMD <3 % was associated with an increased hazard of the combined endpoint (p=0.04). In multivariate analysis, adjusted for age, gender, IHD and body mass index, no association between FMD and the combined endpoint was found (p=0.99). Conclusion: FMD is associated with IHD, but has no independent prognostic effect in patients with chest pain.

Intracardiac Low-Energy versus Transthoracic High-Energy Direct-Current Cardioversion of Atrial Fibrillation: A Randomised Comparison

Of 54 patients with long-standing atrial fibrillation (mean duration 8.3 months), 27 patients were randomised to transvenous low-energy intracardiac biphasic direct-current (DC) cardioversion (ICV) using a single-lead balloon-tipped catheter, and 27 patents were randomised to conventional high-energy transthoracic monophasic DC cardioversion (TCV). ICV was performed with increasing energy levels (7.5–10–12.5–15 J) during mild sedation. TCV was performed with 200–360–360 J during general anaesthesia. Cardioversion to sinus rhythm occurred in 93% (25/27) following ICV and in 67% (18/27) following TCV (p = 0.04). Due to the higher cardioversion rate following ICV, more patients were in sinus rhythm during 180 days of follow-up (log rank test, p = 0.04). Low-energy intracardiac cardioversion represents a highly efficacious alternative to high-energy transthoracic cardioversion.