Dutch TIA 1993.

Methods	Randomized double‐blind, placebo‐controlled trial conducted in hospital in Netherland. No run‐in period in the study design
Participants	1473 patients age > 65 years (range not reported); 64% male with TIA or nondisabling stroke TIAs should not include loss of consciousness, convulsions, incontinence, or prominent headache. Time course: the symptoms should develop within a few seconds, should not progress from one part of the body to another in an orderly march, and should last between 1 minute and 24 hours. Mean baseline BP 158/91 mmHg. Race not stated Exclusions: cerebral ischemia from identifiable causes other than arterial thrombosis or arterial embolism, patients with a contraindication against or a strict indication for a beta‐blocker, last TIA > 3 months before, disorders that may mimic cerebral ischemia, factors likely to confound interpretation of the results. Follow‐up: 2.6 years
Interventions	Treatment: atenolol 50 mg daily Control: Identical placebo tablet
Outcomes	Mortality, CHD, stroke, total CV events
Notes	Percentage on assigned treatment at end of study: Beta‐blocker arm: 71% at 2 years (64% at 3 years); Placebo: 75% at 2 years (68% at 3 years) Inappropriate sample size calculation ‐ "...as the size of the Dutch TIA trial was determined primarily by the number of patients required for the aspirin study."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Double‐blind and placebo‐controlled randomized clinical trial." "Balance between treatment allocations within hospitals was achieved by the use of random permuted blocks; blinded randomization codes were distributed by telephone." Comment: baseline characteristics were well matched.
Allocation concealment (selection bias)	Low risk	Quote: "Balance between treatment allocations within hospitals was achieved by the use of random permuted blocks; blinded randomization codes were distributed by telephone." Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Double‐blind and placebo‐controlled randomized clinical trial. Atenolol was supplied as 50 mg tablets to be taken once a day; placebo tablets had identical appearance and taste." Comment: participants and the treating physicians were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "All outcome events were independently classified by at least three members of the Auditing Committee for Outcome Events, without knowledge of treatment allocation. All possible adverse effects as reported by the patients were recorded; the physicians inquired about such effects in a general fashion." Comment: outcome assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "All patients had their last follow‐up visit between March 1, 1990, and June 30, 1990; the mean duration of follow‐up was 32 months, with a minimum of 12 and a maximum of 52 months. No patient was lost to follow‐up." "The primary data analysis was based on the intention‐to‐treat principle; whether or not medication was taken, patients were analyzed in their originally allocated treatment group until the last follow‐up visit." Comment: No attrition bias as all patients were included in an ITT analysis.
Selective reporting (reporting bias)	Low risk	All the primary outcomes (occurrence of death from the vascular causes, nonfatal stroke, or nonfatal myocardial infarction, whichever occurred first), secondary outcomes (death from all causes, death from vascular causes, plus nonfatal stroke), tertiary outcomes (fatal stroke, the combination of fatal and nonfatal stroke, cardiac death, and the combination of cardiac death and nonfatal myocardial infarction) analyses, along with the adverse effects were reported. Comment: Although protocol was not available, probably all outcomes were reported.
Other bias	Unclear risk	Conflict of interest was not reported.