One hundred and six studies with 125 comparison arms (99,469 participants) were included in the review. Sixteen trials were at high risk of bias; the others were either low or intermediate risk of bias. Follow-up ranged from one to 66 months; for most trials follow-up was six months or less.
Incidence of peripheral oedema: At mean follow-up of 27 weeks and compared to control with a peripheral oedema rate of 3.2% (95% CI 3.1 to 3.3), CCBs were associated with a significantly higher peripheral oedema rate (10.7%, 95% CI 10.6 to 10.9; number of studies not reported). Incidence of peripheral oedema increased with duration of CCB therapy from 2.3% at four weeks to 23.8% at 26 weeks or greater (number of studies not reported).
Dosage of CCB significantly influenced peripheral oedema rates: incidence of oedema was 5.7% (95% CI 5.5 to 5.9) with low-dose CCBs and 16.1% (95% CI 15.9 to 16.3) with high-dose CCBs (number of studies not reported).
Compared to non-DHPs with a oedema rate of 3.1% (95% CI 2.8 to 3.4), DHPs were associated with a significantly higher incidence of peripheral oedema (12.3%, 95% CI 12.2 to 12.5; number of studies not reported). Compared to traditional DHPs, the risk of peripheral oedema with lipophilic DHPs was significantly lower (RR 0.43, 95% CI 0.34 to 0.53; six trials, no heterogeneity).
Patient withdrawal due to peripheral oedema: Compared to control with a patient withdrawal rate of 0.5% (95% CI 0.36 to 0.58), CCBs were associated with a significantly higher patient withdrawal rate (2.1%, 95% CI 1.9 to 2.2; 39 trials). Incidence of patient withdrawal increased with duration of CCB therapy from 1% at four weeks to 5.5% with long-term use (number of studies not reported).
Compared to non-DHPs with a withdrawal rate of 0.6% (95% CI 0.35 to 0.85), DHPs were associated with significantly higher withdrawal rates (2.4%, 95% CI 2.2 to 2.5; number of studies not reported). Compared to traditional DHPs, the risk of withdrawal with lipophilic DHPs was significantly lower (RR 0.22, 95% CI 0.12 to 0.40; six trials).
There was no evidence of publication bias.