Results from two new studies from the United States and Australia indicate that calcium antagonists are inferior to other types of antihypertensive in reducing some of the major complications of hypertension.
The findings may have significant implications for prescribing, particularly in terms of drug costs, according to an author of the US study. Professor William Applegate says: "Although many hypertensive patients will continue to require calcium channel blocker therapy, if just half of the estimated 28 million users of calcium channel blockers worldwide were switched to low-dose diuretics, the costs savings (wholesale) might be as much as $11bn a year worldwide."
The first study was a meta-analysis that included trial results comparing calcium antagonists with other antihypertensive drugs in over 27,000 patients. It concluded: "On the basis of these data, the longer-acting calcium antagonists cannot be recommended as first-line therapy for hypertension." Trials included in the meta-analysis compared a calcium antagonist (most commonly a
dihydropyridine such as nifedipine) with a diuretic, b-blocker, angiotensin converting enzyme (ACE) inhibitor or clonidine. Professor Marco Pahor (Sticht centre on ageing, Wake Forest university, North Carolina, US) and colleagues found that, compared with other antihypertensives, treatment with calcium antagonists had a significantly higher risk of acute myo-cardial infarction (odds ratio, 1.26), congestive heart failure (odds ratio, 1.25) and combined major cardiovascular events (odds ratio, 1.10). No significant differences were found for stroke or all-cause mortality.
The researchers comment that the results are surprising because they found no significant differences in the control of systolic or diastolic blood pressure between the drug groups. This suggested that mechanisms that did not involve reducing blood pressure were important in at least part of the therapeutic effects of antihypertensive treatments. They comment: "Low-dose diuretics, which have proven efficacy and low cost, should continue to be the standard therapy for hypertension, and all new classes of drugs should be compared with diuretics." They add that for combinations of antihypertensive therapies, reliance on classes known to be superior -low-dose diuretics, b-blockers and ACE inhibitors -seems "prudent" (Lancet 2000; 356:1949).
The second meta-analysis, conducted by the Australian Blood Pressure Lowering Treatment Trialists' Collaboration, provides support for ACE inhibitor therapy. Results from placebo controlled trials of ACE inhibitors involving a total of over 12,000 patients showed that risk of stroke was reduced by 30 per cent, coronary heart disease by 20 per cent and major cardiovascular events by 21 per cent. When ACE inhibitors were compared with diuretic-based or b-blocker-based regimens, there was no detectable difference in risk of outcomes between the treatments.
For calcium antagonists, the study found that, compared with diuretics and b-blockers, there was a 13 per cent lower risk of stroke and a 12 per cent greater risk of coronary heart disease events of borderline significance. There were no significant differences between the groups in relative risk of heart failure, major cardiovascular events and cardiovascular deaths or in total mortality (ibid 2000;356:1955).
In an accompanying leading article, Dr Jiang He and Dr Paul Whelton (Tulane university school of public health and tropical medicine and school of medicine, US) say that the findings "indicate the need for caution in recommending calcium antagonists as initial antihypertensive drug therapy in populations at high risk of coronary heart disease and heart failure (ie, western populations)". However, the class may be more appropriate for patients at high risk of stroke and low risk of coronary heart disease, such as Asian populations, they add (ibid 2000;356:1942).