Fifteen trials (n=12,843) were included. Sample sizes ranged from 135 to 5,292 participants. Trial duration was from two to five years. Seven of the 11 trials that provided data on cardiovascular outcomes used suitable methods for randomisation; four explicitly described the allocation concealment method. Ten trials provided details of withdrawals and losses to follow-up. All 11 studies reported levels of compliance; generally studies reported compliance of more than 75% in participants who were taking tablets at study completion. No statistical heterogeneity was reported for any of the analyses.
Individual patient data analysis (five studies, n=8,151): Risk of myocardial infarction in patients allocated to calcium increased by 31% (HR 1.31, 95% CI 1.02 to 1.67, NNT=69). No statistically significant increases occurred in incidence of stroke (HR 1.20, 95% CI: 0.96 to 1.50) or the composite end point of myocardial infarction, stroke or sudden death (HR 1.18, 95% CI 1.00 to 1.39) or death (HR 1.09, 95% CI 0.96 to 1.23).
Subgroup analyses showed that a calcium intake above the median of 805mg/day was significantly associated with an increased risk of myocardial infarction. Further results were reported.
Trial summary data analysis: There was a statistically significant increase in incidence of myocardial infarction following treatment with calcium (RR 1.27, 95% CI 1.01 to 1.59, I2=0%; seven studies). No increased risk was found for stroke, death or the composite end point. There was no evidence of publication bias.