Seventy RCTs (324,168 participants) were included in the review. Risk of bias was recorded. It appeared that most trials met criteria for adequate sequence generation, allocation concealment and blinding. Mean follow-up was 3.5 years (range one to nine years). The reported drop-out rate was below 10%. Compliance rate ranged from 65% to 100%.
In the network meta-analysis, risk of cancer was found to be statistically significant for the combination of ACEi and ARBs compared to placebo (OR 1.14, 95% CI 1.02 to 1.28), but only when the fixed-effect model was used. There was no difference in risk of cancer with any of the other drugs compared to placebo. Statistically significant differences were reported for combination treatment compared to ARB alone, ACEi, beta-blockers and diuretics in terms of cancer risk and compared with ACEI for cancer-related death.
Direct comparison meta-analysis was consistent with network meta-analysis results for all comparisons except the combination of ACEi and ARBs compared to ACEis alone (OR 1.16, 95% CI 1.05 to 1.28) and CCBs compared to ARBs (OR 1.18, 95% CI 1.04 to 1.33); these comparisons were significantly associated with risk of cancer. There were no other statistically significant associations between antihypertensive drug class treatments on risk of cancer or cancer-related death.
The trial sequential analysis showed no evidence of a 5% to 10% increased risk of cancer in any individual drug class, but there was a possibility of a 10% increase in cancer risk following treatment with combination ACEi and ARB (this result was driven largely by one trial).
Sensitivity and subgroup analyses did not materially alter the main results. Statistical heterogeneity was reported as low to moderate. There was no evidence of publication bias.