Calcium channel blockers and headache

Abstract

We recently reported a meta-analysis of 94 randomized placebo-controlled trials of blood pressure-lowering drugs in which the prevalence of headache was reported [1]. On average, one-third fewer people reported headache in the treated groups than in the placebo groups [odds ratio (OR) 0.67; 95% confidence interval (CI) 0.61, 0.74; P < 0.001]. There was a statistically significantly reduced prevalence of headache in separate analyses of four classes of blood pressure-lowering drugs, thiazides, β -blockers, ACE inhibitors and angiotensin-II receptor antagonists, an observation that suggested that blood pressure reduction itself prevents headache.We excluded calcium channel blockers in this analysis because they are likely to affect the prevalence of headache in two opposite ways, tending to reduce the prevalence because they lower blood pressure but to increase it because they cause vasodilation. We here present the results on calcium channel blockers and headache, the net effect according to dose, from our meta-analysis of randomized trials [1,2].There were 60 randomized placebo-controlled trials of calcium channel blockers in fixed dose that recorded data on headache, with 99 treatment groups and 8087 participants in total. We divided the 99 treatment groups into three categories according to dose: standard dose (as previously defined [2], 31 treatment groups), below standard dose (median 0.6-fold, 27 treatment groups) and above standard dose (median 2.2-fold, 41 treatment groups). We analysed the data as previously reported [1], calculating the OR (odds of headache:no headache in participants allocated calcium channel blockers divided by that for placebo) for each category.The effect on headache showed a striking effect of dose (see Figure 1), with a trend which was statistically significant ( P = 0.03). Calcium channel blockers reduced headache at low (below standard) dose (OR 0.92, 95% CI 0.71, 1.2), increased it at high (above standard) dose (OR 1.33, 95% CI 0.99, 1.77) and had an intermediate effect at standard dose (OR 1.18, 95% CI 0.93, 1.49).The effect of dose on the risk of headache supports the two opposing actions. The increase in risk caused by vasodilation is likely to be strongly dose dependent, because the prevalence of other symptoms caused by

Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies

“…Calcium channel blockers seem to be less effective than other drugs in heart failure but the difference in risk reduction is not large (19% v 24%; table 6) and they are no less effective after myocardial infarction. All classes of drug prevent headaches and migraine,48 49 50 although calcium channel blockers do so only in low (half standard) dose 51. There is no evidence to support recommendations for particular classes of drug in older or younger people 47.…”

“…All classes of drug prevent headaches and migraine, 48 49 50 although calcium channel blockers do so only in low (half standard) dose. 51 There is no evidence to support recommendations for particular classes of drug in older or younger people. 47 A relative contraindication of even cardioselective β blockers in people with airways obstruction or peripheral arterial disease is perceived, 24 but a meta-analysis of trials has shown that cardioselective β blockers do not produce adverse respiratory effects in mild to moderate obstructive airways disease 52 ; such considerations are not a reason to withhold a β blocker, but reinforce the principle that patients should be monitored for side effects of drugs and a drug should be withdrawn if it causes adverse effects.…”

Hypertension and Headache: the Effect of Antihypertensive Drugs

“…Головная боль может быть и нежелательной побочной реакцией (НПР) при применении дигидропиридиновых АК, при этом она является дозозависимой. Поэтому головная боль как НПР может отсутствовать при назначении препаратов этой группы в стартовых дозах, а при увеличении дозы вероятность ее появления значительно возрастает [10]. Головная боль как побочный эффект АК обусловлена их главным механизмом действия -вазодилатацией [9,10].…”

Adverse drug reactions – no farewell to harms

“…The second, and more important, reason is that effects that appear not to be dose‐related are saturated in the therapeutic range but are dose‐related in the range of doses below the therapeutic range; in other words, they are hypersusceptibility reactions [6]. Most adverse reactions, however, are dose‐related within the therapeutic range of doses (collateral reactions), and an elegant example of this is given by Law et al in this issue of the Journal , in which they show that headache due to calcium channel blockers is dose‐related [7]. That they have shown this by a meta‐analysis of published data should encourage others to look for dose relationships elsewhere in the published literature.…”