Randomised controlled trials (RCTs) that compared inhaled tiotropium bromide with placebo or long-acting beta agonists or long-acting beta agonists plus inhaled corticosteroid were eligible for inclusion in the review. Trials had to be more than four weeks duration. The patients of interest were adults, aged at least 35 years, with stable chronic obstructive pulmonary disease according to American Thoracic Society/European Respiratory Society or GOLD (Global Initiative for Chronic Obstructive Lung Disease) diagnostic criteria.
The primary eligible outcomes were: major adverse cardiovascular composite measurement including non-fatal myocardial infarction, stroke, and cardiovascular death during the treatment period. These individual components were also measured separately. All-cause mortality was eligible as a secondary outcome.
The mean age of included patients was 64.8 years, and 74% were men. In the majority of included trials, tiotropium was administered once a day and was compared with placebo. The other included comparators were salmeterol, or salmeterol/fluticasone. Trial duration ranged from two to 48 months.
All reviewers independently selected trials for inclusion, and disagreements were resolved by consensus.