ABSTRACT
BACKGROUND: We evaluated whether the risk of stroke depends on aspirin dose in patients with a previous transient ischemic attack or stroke. METHODS: We conducted a metaregression analysis of stroke by using published randomized, placebo-controlled trials. We analyzed studies of patients who had recently had a transient ischemic attack or stroke (ie, secondary prevention). We abstracted data on the treatment regimen and stroke. To evaluate the dose-response relationship, we conducted a metaregression analysis of study-specific risk ratios by means of weighted linear regression. RESULTS: Eleven randomized, placebo-controlled trials contributed a total of 5228 patients randomized to aspirin only and 4401 patients randomized to placebo only. The slope of the dose-response curve was virtually flat across a wide range of aspirin doses from 50 to 1500 mg/d (P = .49 for test of slope not =0). Summarizing across studies, aspirin decreases the risk of stroke by about 15% (risk ratio, 0.85;95% confidence interval, 0.77-0.94). CONCLUSIONS: Aspirin reduces the risk of stroke by approximately 15%, and this effect is uniform across aspirin doses from 50 to 1500 mg/d. The lowest effective aspirin dose has not yet been identified, but it could be lower than 50 mg/d.
Subject(s)
Aspirin/administration & dosage , Cerebrovascular Disorders/prevention & control , Fibrinolytic Agents/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Aged , Dose-Response Relationship, Drug , Female , Humans , Linear Models , Male , Middle Aged , Odds Ratio , Randomized Controlled Trials as Topic , RiskABSTRACT
To estimate the frequency of adverse effects associated with the use of the transdermal nicotine patch, we abstracted and analysed data from 47 reports of 35 clinical trials. The meta-analysis presented here represents a synthesis of data from 41 groups of nicotine patch recipients totalling 5501 patients, and 33 groups of placebo recipients totalling 3752 patients. Smoking abstinence was the primary outcome in 32 of the trials, and relief of colitis symptoms was the primary outcome in 2 of the trials; 1 study of contact sensitisation was included in the skin irritation analysis. The patch was clearly effective as an aid to smoking abstinence. Despite the large number of patients in the analysis, few adverse cardiovascular outcomes (myocardial infarction, stroke, tachycardia, arrhythmia, angina) were reported, and no excess of these outcomes was detected among patients assigned to nicotine-patch use. The incidences of several minor adverse effects were clearly elevated among the nicotine-patch groups, especially sleep disturbances, nausea or vomiting, localised skin irritation and respiratory symptoms, but the background rates and risk ratios varied considerably across studies. The incidence of nausea or vomiting appeared to be lowest when the patch dose was tapered. The results of this meta-analysis indicate that very large studies would be needed to assess the effect of the patch, if any, on serious, rare outcomes. These results also suggest that the rate of minor adverse effects might be lowered by modifying patch-use protocols.
Subject(s)
Drug Delivery Systems , Nicotine/adverse effects , Nicotinic Agonists/adverse effects , Tobacco Use Disorder/drug therapy , Administration, Cutaneous , Cardiovascular Diseases/chemically induced , Dermatitis, Contact/etiology , Female , Humans , Male , Nausea/chemically induced , Randomized Controlled Trials as Topic , Regression Analysis , Respiration/drug effects , Risk Assessment , Sleep Wake Disorders/chemically induced , Smoking Cessation/methods , Vomiting/chemically inducedABSTRACT
To evaluate the hypothesis of increased kidney cancer risk after exposure to hydrocarbons, especially those present in gasoline, we conducted a case-control study in a cohort of approximately 100,000 male refinery workers from five petroleum companies. A review of 18,323 death certificates identified 102 kidney cancer cases, to each of whom four controls were matched by refinery location and decade of birth. Work histories, containing an average of 15.7 job assignments per subject, were found for 98% of the cases and 94% of the controls. To each job, industrial hygienists assigned semiquantitative ratings for the intensity and frequency of exposures to three hydrocarbon categories: nonaromatic liquid gasoline distillates, aromatic hydrocarbons, and the more volatile hydrocarbons. Ratings of "present" or "absent" were assigned for seven additional exposures: higher boiling hydrocarbons, polynuclear aromatic hydrocarbons, asbestos, chlorinated solvents, ionizing radiation, and lead. Each exposure had either no association or a weak association with kidney cancer. For the hydrocarbon category of principal a priori interest, the nonaromatic liquid gasoline distillates, the estimated relative risk (RR) for any exposure above refinery background was 1.0 (95% confidence interval [CI] 0.5-1.9). Analyses of cumulative exposures and of exposures in varying time periods before kidney cancer occurrence also produced null or near-null results. In an analysis of the longest job held by each subject (average duration 9.2 years or 40% of the refinery work history), three groups appeared to be at increased risk: laborers (RR = 1.9, 95% CI 1.0-3.9); workers in receipt, storage, and movements (RR = 2.5, 95% CI 0.9-6.6); and unit cleaners (RR = 2.3, 95% CI 0.5-9.9).
