Adverse reactions attributed to sumatriptan

There are several reports on cardiac adverse reactions attributed to the antimigraine drug sumatriptan in the recent literature. In order to assess the frequency and the character of adverse reactions to sumatriptan, a postmarketing cohort study was performed one year after registration of the drug in The Netherlands. With assistance of 86% of the drug dispensing general practitioners in The Netherlands, 1727 patients who had received sumatriptan were traced in July, 1992. Via their general practitioners, a questionnaire about use of sumatriptan, adverse reactions and other medication was sent to the patients in December 1992. During the study period, seven patients were lost to follow-up. Of the 1720 remaining patients, 1202 (70%) responded to the questionnaire, of whom 1187 had actually used sumatriptan. The most frequently reported suspected adverse reactions were paraesthesiae (139 patients, 95% CI 9.9%–13.5%) and dizziness (96 patients, 95% CI 6.5%–9.7%). Chest pain after use of sumatriptan was reported by 94 patients (7.9%, 95% CI 6.4%–9.4%), and according to the close temporal relationship with the intake of sumatriptan and a positive rechallenge, a causal relationship was probable in most of those patients. The frequency of chest pain attributed to sumatriptan was higher in females (9.0% vs 4.6%; relative risk 1.9, 95% CI 1.1–3.4). Age and hypertension were not associated with chest pain attributed to sumatriptan. Dyspnoea attributed to sumatriptan was reported by 26 patients (2.2%), and was associated with obstructive lung disease (relative risk 5.4 95% CI 1.7–16.9). Thus, in view of the high frequency of chest pain after use of sumatriptan and reports in the literature of cardiac disturbances, including myocardial infarction, cautious use of the drug is advised.     

Impact of randomized trials comparing conventional and endovascular abdominal aortic aneurysm repair on clinical practice.

PURPOSE: To report a retrospective study into the effects of trials on clinical decision-making regarding abdominal aortic aneurysm (AAA) patients suitable for both conventional open (OR) and endovascular aneurysm repair (EVAR). METHODS: A questionnaire was sent to 1400 Dutch surgeons and trainees. Interviewees had to choose between OR and EVAR for AAA patients with and without comorbidity. Specifically, their preferences before and after the publication of 2 randomized trials (EVAR-1 and DREAM) were polled. RESULTS: Of the 524 (37%) questionnaires returned, 223 (43%) respondents treated AAA patients. Before publication of the trials, 160 (72%) preferred OR for the patient without comorbidity and 169 (76%) preferred EVAR for the patient with comorbidity. In total, 72 (32%) respondents changed their preference after the trials were published; however, there was no overall major shift. Focusing on the different cases revealed that the OR preference was significantly enhanced for the patient without comorbidity (p<0.01), while the EVAR preference was significantly enhanced for the patient with comorbidity (p<0.05). CONCLUSION: The randomized trials have not induced major overall changes in surgical decision-making for AAA patients suitable for both EVAR and OR.     

Measuring quality of life in patients with myocardial infarction or stroke: a feasibility study of four questionnaires in The Netherlands.

OBJECTIVE--To test in patients with a history of myocardial infarction or stroke the feasibility of four quality of life measurements--the Nottingham health profile (NHP), the heart patients psychological questionnaire (HPPQ), the sickness impact profile (SIP), and the hospital anxiety and depression scale (HAD). DESIGN--Subjects were tested and retested after an interval of 14 days: questionnaires were self assessed. SUBJECTS--Participants were randomly selected from the Rotterdam stroke data bank (stroke patients; n = 16, mean (SD) age 66.0 (11.0) years and from the population based Rotterdam study (myocardial infarction; n = 20, mean (SD) age 72.7 (7.9) years, controls; n = 17, mean (SD) age 72.8 (7.3) years. MEASUREMENTS AND MAIN RESULTS--Mean (SD) administration times for the NHP, HPPQ, SIP, and HAD were 7.9 (3.5), 10.5 (4.3), 21.0 (9.8), and 5.5 (2.8) minutes respectively. On average, the test-retest reliability was good, with Spearman correlations ranging from 0.31 to 0.95. In spite of the limited size of the study, all instruments were able to show differences between the study groups. For instance, median SIP total scores for myocardial infarction and stroke patients were 12.4 (interquartile range 7.0-19.1) and 11.4 (5.9-15.4) respectively, compared with 7.7 (3.7-11.3) in the control group (p values of 0.04 and 0.14 respectively). CONCLUSIONS--This study suggests that use of the four instruments tested may be feasible and reliable for assessing aspects of quality of life in patients with a history of a myocardial infarction or stroke.     

Does the beneficial effect of HRT on endothelial function depend on lipid changes

OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.     

Soy isoflavones, body composition, and physical performance

OBJECTIVES: Physiologic changes, occurring during the process of aging, can have serious health consequences, such as increased risk of chronic disease and disability. Decline in estradiol levels after menopause is hypothesized to contribute to this risk. Thus, hormone therapy (HT) might prevent or delay those changes. However, HT has serious side effects and alternative approaches are needed. METHODS: We performed a 12-month double-blind randomized trial comparing soy protein containing 99mg isoflavones (aglycone weights) with milk protein (placebo) daily in 202 postmenopausal women aged 60-75 years. Endpoints were body composition, and physical performance. Randomization resulted in reasonable well-balanced groups, 153 (76%) women completed the trial. Compliance was good (plasma genistein levels 55 +/- 101 and 1259 +/- 1610 nmol/L for placebo and soy group, respectively). The changes in the endpoints during the intervention period among the two intervention groups were analyzed. RESULTS: Body mass index (BMI) and waist-to-hip ratio did not change during intervention. Handgrip strength at the final visit was slightly worse in the soy group compared to the placebo group (-0.45 kg (95% C.I.: -2.5, 1.6 kg; p = 0.7), but this difference was not statistically significant. Self-reported functional status, mobility and physical performance, all slightly improved during intervention but there were no differences between the groups. CONCLUSIONS: The results of the present trial do not support the view that soy isoflavones have favorable effects on body composition and physical performance in postmenopausal women.     

Classification of heart failure in population based research: An assessment of six heart failure scores

Several scores based on symptoms and signs have been developed to assess the presence of heart failure. The goal of this study was to compare six heart failure scores in non-hospitalised subjects and to determine their usefulness in population based research. The scores were applied to 54 participants of a population based study. All underwent a complete medical examination, including chest X-ray, electrocardiography and Doppler echocardiography. Using all information available, a cardiologist, unaware of the results of the scores, clinically classified participants as having no, possible or definite heart failure. Sensitivity, specificity, predictive values and receiver operating characteristics were calculated, using the cardiologist's assessment as a gold standard. The cardiologist judged definite or possible heart failure to be present in 17 persons. All scores had a high sensitivity for the detection of definite heart failure, whereas the study of men born in 1913 and Walma's score had the highest sensitivity for the combination of possible and definite heart failure. Gheorgiade's and the Boston score had the highest positive predictive values. In conclusion, five of the six scores we studied are broadly similar in the detection of heart failure. The men born in 1913 score relies heavily on the assessment of dyspnea, resulting in a relatively large number of false positives. Although the scores are useful in detecting manifest heart failure, objective measurements of cardiac function appear necessary to reduce the false positive rate and accurately detect early stages of heart failure.     

Hormone replacement therapy and intima-media thickness of the common carotid artery: the Rotterdam study

BACKGROUND AND PURPOSE: Observational data suggest that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular disease in healthy postmenopausal women. The mechanisms underlying this protection are not entirely clear but may include inhibition of the atherosclerotic process. METHODS: We studied the association between ever use of HRT and intima-media thickness (IMT) of the common carotid artery in 1103 naturally menopausal women, aged 55 to 80 years, in the Rotterdam Study, a community-based cohort study in a suburban area of Rotterdam, Netherlands. Mean and maximum IMT of the common carotid artery were measured noninvasively with B-mode ultrasound. RESULTS: Ever use of HRT for >/=1 year was associated with a decreased mean and maximum IMT compared with never users (mean IMT, 0.719 mm [SE 0.01] versus 0. 742 mm [SE 0.004], P=0.03; maximum IMT, 0.952 mm [SE 0.015] versus 0. 983 mm [SE 0.006], P=0.04), after adjustment for age, smoking, educational level, systolic blood pressure, and body mass index. No association was found for use <1 year (mean IMT, 0.739 mm [SE 0.013] versus 0.742 mm [SE 0.004], P=0.69; maximum IMT, 0.990 mm [SE 0.019] versus 0.983 mm [SE 0.006], P=0.75). Additional adjustment for diabetes, frequency of visits to healthcare facilities, or total and HDL cholesterol did not change these results. CONCLUSIONS: The findings of this population-based study show that ever use of HRT is associated with a decreased IMT in the common carotid artery in elderly women.     

Fibrinolytic activity in peripheral atherosclerosis in the elderly

Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of D-dimer have jointly been found in subjects with cardiovascular disease. To understand this apparent paradox of increased inhibition of fibrinolysis (high PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue type plasminogen activator (t-PA) in subjects with varying severity of peripheral atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of 7983 men and women aged 55 years and over, the ankle to brachial systolic blood pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were measured. T-PA antigen and t-PA activity were, independent from each other, increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis). PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below 50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In contrast to current beliefs, we found that only a fraction of the variation of t-PA antigen was due to the variation in circulating PAI-1 antigen. A slight positive association was observed between t-PA antigen and D-dimer. PAI-1 and t-PA activity were not associated with D-dimer concentration. In conclusion, in subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t-PA activity) appear to be required to increase circulating D-dimer. This suggests that increased D-dimer levels in subjects with atherosclerosis do not reflect increased inhibition, but rather reflect increased fibrinolysis.     

Preoperative outpatient evaluation of young adults by anesthesiologist: anamnesis and physical examination are satisfactory--short questionnaire of Dutch Public Health Council is not

The report of the Netherlands Health Council 'Preoperatief onderzoek; een herijking van uitgangspunten' recommends that the health status of patients aged 16-39 years can be investigated preoperatively by the anaesthesiologist using a short questionnaire (6 questions). However, it is not clear whether such an abbreviated preoperative investigation will be informative enough for a safe and balanced anaesthesiologic management. An overview of relevant literature on the subject of preoperative investigation indicates that the preoperative physical status of patients as reflected by the American Society of Anesthesiologists (ASA) classification is a predictor of perioperative complications. Patients can be classified accordingly on the basis of an extended history and physical examination only: any routine additional investigation, such as ECG, chest X-ray or laboratory investigations, seem superfluous. Only blood group, rhesus factor and the presence of irregular antibodies may need to be determined if indicated by the kind of surgery. Currently, however, there is not sufficient evidence to demonstrate that the short questionnaire of the Netherlands Health Council is informative enough.