Plasma concentrations of antipsychotics and QTc prolongation: a pilot study.

Background: Certain antipsychotics are known to cause QTc interval prolongation, which has been associated with increased risk of arrhythmia and sudden death. Previous studies have investigated whether there is an association between oral antipsychotic dose and QTc interval prolongation, however only few have examined the association between antipsychotic plasma concentrations and QTc interval.Material and methods: We performed a cross-sectional study with 22 forensic psychiatric in-patients. We measured the plasma concentration of the prescribed antipsychotics and performed an ECG simultaneously. We used Bazett's formula to calculate QTc and defined QTc as prolonged when: >460 ms for women and >450 ms for men.Results: Seventy-seven percent (n = 17) of the subjects were men (mean age = 40 years) and 91% (n = 20) were diagnosed with schizophrenia. QTc's ranged from 369 to 437 ms. Patients receiving QTc prolonging drugs had significantly greater QTc interval compared to patients receiving non-prolonging drugs. Weak to moderate negative correlations were found between QTc interval and both defined daily dose (DDD) and antipsychotic plasma concentration. There was no statistical difference between the correlations for DDD and plasma concentration versus QTc interval.Conclusion: We did not find a stronger association between antipsychotic plasma concentration and QTc than between antipsychotic dose and QTc. We suggest close monitoring with regular electroencephalogram's until the development of a better marker for predicting the risk of cardiac arrhythmia.

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.

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.