High-dose calcium channel blockers could be best stroke prevention
MedWire News: Antihypertensive drugs have a dose-dependent effect on blood pressure (BP) variability, with high doses of calcium channel blockers having the largest effect, shows a systematic review.
Previous research by Peter Rothwell (University of Oxford, UK) and colleagues showed that BP variability predicts stroke and is affected by which particular antihypertensive agent patients use. They found that BP variability is reduced by calcium channel blockers and by nonloop diuretics, but increased by angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and beta blockers - especially the nonselective forms.
The latest systematic review, by Rothwell and Alastair Webb (University of Oxford), further examines the effects of specific antihypertensive drugs. Interindividual variance in systolic BP, calculated from the standard deviation and expressed as a variance ratio (VR) was used as a surrogate for intraindividual BP variability.
The team reports in the journal Stroke that calcium channel blockers had the largest beneficial effect on BP variability. They reduced BP variability when added to another antihypertensive agent, with a VR of 0.75 (based on 12 trials with 1565 patients).
Adding a diuretic to another agent also reduced BP variability, although to a lesser extent, with a VR of 0.85 (17 trials with 3217 patients).
By contrast, adding other antihypertensive agents to calcium channel blockers (in 12 trials with 1460 patients) did not affect BP variability, despite causing an average 5.8-mmHg reduction in systolic BP.
The dose of antihypertensive agent was also important, say Rothwell and Webb. Giving patients a higher versus a lower dose of a calcium channel blocker (in 25 trials with 2179 patients) reduced BP variability, with a VR of 0.84.
But giving patients a higher versus a lower dose of a beta blockers (six trials with 486 patients) increased their BP variability, with a VR of 1.31.
Based on their previous findings, the researchers suggest that high-dose calcium channel blockers, alone or with other agents, may be effective against stroke.
Editorialist Alberto Zanchetti (University of Milan, Italy) said that the research into BP variability has "been a welcomed challenge to common opinion, because common opinion does not necessarily mean a correct opinion."
He said: "Rothwell and his associates deserve recognition for having raised an issue of the upmost conceptual and practical importance."
However, Zanchetti questioned whether interindividual BP variability, as measured in the current study, can be reasonably used as a surrogate for intraindividual BP variability, especially for small trials of short duration. He noted that the two measures may indicate different things, despite being correlated.
"The issue deserves to be studied in depth without hurrying to premature conclusions," Zanchetti concluded.
"More reliable indices of 'real' blood pressure variability from day to day through the many years of treatment must be elaborated and investigated… and a better understanding of the phenomena underlying the current variable definitions of variability should be achieved."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Eleanor McDermid