Amlodipine increased peripheral edema compared to placebo (16.6% vs 6.2%; RR 2.9, 95% CI 2.50-3.36, P<0.0001), but reduced headache incidence (7.9% vs 10.9%; RR 0.77, P=0.002).
Meta-Analysis (n=7,226)
Does amlodipine increase the risk of peripheral edema and headache compared to placebo in patients with arterial hypertension and stable CAD?
Amlodipine increases the risk of peripheral edema threefold but reduces the incidence of headache, with both effects being dose-dependent.
Effect estimate: RR 2.9 (95% CI 2.50-3.36)
Absolute Event Rate: 16.6% vs 6.2%
p-value: p=<0.0001
OBJECTIVE: Use of amlodipine for treatment of arterial hypertension and stable coronary artery disease (CAD) is sometimes limited by occurrence of peripheral edema and headache. We aimed to explore the true magnitude of this phenomenon by determining the rate and placebo-adjusted rate of these side effects. METHODS: We performed a meta-analysis by including all randomized, placebo-controlled trials reporting edema and headache with amlodipine in patients with arterial hypertension and CAD. Placebo-adjusted rate (%) was determined as follows: (SE amlodipine % - SE placebo %)/SE amlodipine %. RESULTS: Data from 7226 patients of 22 trials were analyzed. Rate of edema was higher on amlodipine vs. placebo (16.6 vs. 6.2%, risk ratio: 2.9, 95% CI: 2.50-3.36, P < 0.0001). The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine. Treatment with low/medium doses (2.5-5 mg) resulted in lower rates of edema (risk ratio: 2.01, 95% CI: 1.41-2.88, P = 0.0001) vs. high dose (10 mg) (risk ratio: 3.08, 95% CI 2.62-3.60, P < 0.0001, Pforinteraction = 0.03). Incidence of headache was reduced using amlodipine vs. placebo (7.9 vs. 10.9%, risk ratio: 0.77, 95% CI: 0.65-0.90, P = 0.002) and was driven by use of low/medium doses (risk ratio: 0.52, 95% CI: 0.40-0.69, P < 0.00001 vs. risk ratio: 0.92, 95%-CI: 0.74-1.15, P = 0.45, for high doses, Pforinteraction = 0.002). CONCLUSION: Although risks of peripheral edema are three-fold higher on amlodipine, up to one-third of edema cases on amlodipine might not be induced by amlodipine. Headache is reduced on amlodipine treatment, mainly driven by use of this drug at low/medium doses.
Vukadinović et al. (Fri,) conducted a meta-analysis in Arterial hypertension and stable coronary artery disease (CAD) (n=7,226). Amlodipine vs. Placebo was evaluated on Rate of peripheral edema (RR 2.9, 95% CI 2.50-3.36, p=<0.0001). Amlodipine increased peripheral edema compared to placebo (16.6% vs 6.2%; RR 2.9, 95% CI 2.50-3.36, P<0.0001), but reduced headache incidence (7.9% vs 10.9%; RR 0.77, P=0.002).