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Purpose: To estimate the reduction in all-cause mortality conferred by beta-blockers in a population-based cohort of elderly survivors of myocardial infarction during the year following hospital discharge., Methods: A dynamic retrospective cohort was assembled from persons aged 66 years and over surviving myocardial infarction in Quebec between 1990 and 1993. Information on hospitalizations was linked to medication and physician claims, demographic characteristics and vital status. Subjects prescribed beta-blockers at hospital discharge had fewer comorbid medical conditions, less pre-existing cardiovascular disease and less severe infarcts. To control for these differences, analyzes were restricted to subjects receiving at least one beta-blocker and mortality was compared between periods with and without beta-blocker exposure using Cox proportional hazard models., Results: Among 14,547 survivors of myocardial infarction, 41% were dispensed at least one beta-blocker. Among those subjects, the risk of dying during periods of beta-blocker use was reduced 40% (hazard ratio = 0.6; 95% CI: 0.5, 0.7)., Conclusion: Confounding by indication threatens the validity of observational studies of intended effects of medications. For elderly survivors of myocardial infarction, the estimated benefit of beta-blockers from observational studies is greater than the estimate from randomized trials. Greater benefits do not seem to be an artifact arising from systematically prescribing beta-blockers to subjects with better prognosis. Reducing confounding by indication can enhance the validity of observational studies of medications and widen research applications of administrative health databases. While the actual benefits of medications are never truly known these studies can provide a credible range that brackets the truth.

To assess the duration of antihypertensive effect of a single daily dose of the short-acting diuretic hydrochlorothiazide, a double-blind crossover study was performed in 11 patients previously well controlled with diuretics. Each patient received hydrochlorothiazide 100 mg in the morning for 12 wk and blood pressure were recorded 4 times daily (8 A.M., 12 noon, 4 A.M., and 8 P.M) on 3 separate visits. The crossover design also included a 12-wk placebo period either preceding or following active therapy. Blood pressure control was excellent and sustained throughout the day in all patients studied, indicating that a single daily dose of hydrochlorothiazide is a suitable regimen for hypertension therapy. The use of a placebo period before initiating the trial and during the active part of the trial confirmed the observation that patients who have been adequately treated for long periods will maintain lowered blood pressure for a variable period after stopping therapy.

To compare the antihypertensive efficacy of methyldopa administered once at bedtime with the same total dose given three times daily, a double-blind crossover study was performed in 14 patients previously well controlled on methyldopa. Each patient received a total daily dose of 0.37 gm, 0.75 gm, or 1.5 gm of methyldopa, depending on the dose of drug that had previously been successful in that individual. The trial design included either 12 wk of methyldopa three times daily (TID) followed by 12 wk of single daily bedtime (HS) doses of methyldopa or administration of drug in the reverse order. Supine and erect blood pressures were recorded 4 times daily (8 a.m., 12 noon, 4 p.m., and 8 p.m.) every 4 wk throughout the study. Blood pressure control was excellent in all patients whether the drug was administered three times daily or at bedtime. Systolic pressures were slightly lower at 8 a.m., when methyldopa was given at bedtime than on doses three times daily, and systolic and diastolic pressures were slightly higher at 8 p.m. that at 8 a.m. on the bedtime regimen.