Letters

Inferiority of calcium channel blockers to cheaper drugs

News item was inaccurate on at least two counts

Author's reply

Use of long acting calcium channel blockers is not deleterious in elderly hypertensive patients

News item was inaccurate on at least two counts

EDITORThe news item by Josefson about calcium channel blockers being inferior to cheaper drugs¹ seems to have been taken directly from the press release by the investigators from the Wake Forest University School of Medicine. Nowhere is the lesser incidence of stroke with calcium channel blockers and the equality of total mortality with these and other drugs mentioned. Moreover, the inappropriate inclusion of flawed data in this meta-analysis should be contrasted with the more careful and complete meta-analysis presented by MacMahon and Neal at the International Society of Hypertension on 24 August 2000 and now published in the Lancet.² Since this study was not hyped by press releases, Josefson was probably unaware of its balanced results.

But Josefson goes further. She states that calcium channel blockers are inferior to other antihypertensive drugs in elderly patients with diabetes and systolic hypertension, referring incorrectly to two papers. The first shows exactly the opposite: calcium channel blockers in the Syst-Eur trial provided better protection than did diuretics in the SHEP trial.³ The second paper is the SHEP data with ne'er a calcium channel blocker in sight.⁴

The BMJ should insist on at least as much accuracy in its news articles as in its papers.

Norman M Kaplan, professor of medicine. 
University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, J4, 134, Dallas, TX 75390-8586 ronald.victor{at}emailswmed.edu

Competing interests: NMK has been paid honoraria for talks given under the auspices of multiple pharmaceutical companies that market calcium channel blockers, including Bayer, Astra, Merck, and Pfizer.

Author's reply

EDITORThe literature on calcium channel blockers and the optimal pharmacological treatment of hypertension is long and contentious, and a full analysis of the literature is beyond the scope of a regular news piece and this reply. Clearly, antihypertensive treatment is complex and dependent on side effects as well as concurrent disease and lifestyle.

Kaplan should realise that in my role of reporter, I was merely reporting on a study and not necessarily promoting or defending any of its results. Moreover, I have no interest, vested or otherwise, in the study results. Since at the time of my news piece the study from Wake Forest University had not yet been published (it was presented at a meeting) and I lacked a paper to scrutinise, I was limited in my ability to analyse the data and based my report on an interview with Dr Pahor and on the press release.

None the less, many studies show that calcium channel blockers are inferior to other antihypertensive drugs in preventing some of the cardiovascular complications of hypertension. Moreover, concern has been raised that a financial incentive may be at work because they are heavily promoted above cheaper and arguably equally effective, if not more effective, blood pressure drugs.¹

Some studies single out short acting calcium channel blockers and dihydropyridine derivatives as the culprits. Most people agree that calcium channel blockers are effective antihypertensives and superior to placebo in reducing blood pressure, and I am not suggesting that patients taking them abandon their treatment. However, many meta-analyses have shown that when compared with other antihypertensive drugs, such as angiotensin converting enzyme inhibitors,  blockers, thiazides, and loop diuretics, calcium channel blockers have a higher relative risk of myocardial infarction and stroke.² For example, the ABCD trial compared nisoldipine, a calcium channel blocker, with enalapril, an angiotensin converting enzyme inhibitor, in patients with both non-insulin dependent diabetes and hypertension and also found a greater incidence of myocardial infarction with calcium channel blockers.³ The MIDAS study suggested that the calcium channel blocker isradapine is associated with more strokes and cardiovascular complications than hydrochlorothiazide.⁴

Finally, while I acknowledge a mix-up with the paper by Tuomilehto et al,⁵ I did not mention the SHEP trial by Curb et al. Kaplan seems to have confused this citation with that of the MIDAS trial. Moreover, he does not mention that in the study by Tuomilehto et al nitredipine treatment is not completely segregated from treatment with hydrochlorothiazide and angiotensin converting enzyme inhibitors. Thus many of the patients were taking the calcium channel blocker and enalapril or hydrochlorothiazide, or both, so the results may be confounded.

Deborah Josefson, pathologist and internist. 
Premier Pathology Laboratories and Sierra View District Hospital, 263 N Pearson Drive, Suite 108, Porterville, CA 93257-3333, USA

Competing interests: None declared.

Use of long acting calcium channel blockers is not deleterious in elderly hypertensive patients

EDITORWe read with concern the news item by Josefson which highlighted the belief that calcium channel blockers may be less effective in elderly patients with diabetes and systolic hypertension.¹ We are worried not only that the article was inaccurate but that it may be misinterpreted by the lay press, leading to widespread concern among patients and sometimes discontinuation of antihypertensive treatment without proper medical supervision and advice, as has happened previously.²

Both diabetes and isolated systolic hypertension are associated with a high risk of cardiovascular events. Two recent placebo controlled studies have shown, unequivocally, that reducing blood pressure in elderly patients with isolated systolic hypertension reduces cardiovascular morbidity and mortality. The SHEP study used a diuretic based regimen³ and the Syst-Eur trial used the long acting dihydropyridine calcium channel blocker nitrendipine.⁴ Josefson incorrectly states that calcium channel blockers are less effective in patients with diabetes and systolic hypertension and cites a subgroup analysis of the Syst-Eur study.⁴ As the Syst-Eur study was placebo controlled, it is impossible to draw any conclusions about the relative efficacy of calcium channel blockers compared with other agents in older patients with isolated systolic hypertension. Moreover, the subgroup analysis showed a greater reduction in cardiovascular mortality among the 492 diabetic patients included in the trial.⁴ Interestingly, a similar observation was also made in the SHEP study, which included 583 diabetic patients, who had a 34% reduction in cardiovascular disease compared with the placebo group.³

To date, there have been no comparative studies of antihypertensive treatment in elderly patients with isolated systolic hypertension, with or without diabetes mellitus. However, the STOP-2 trial, which studied a large cohort of elderly patients with hypertension, (systolic pressure >180 mm Hg or diastolic >105 mm Hg, or both), compared a conventional regimen (diuretic or  blocker, or both) with "modern" treatment with an angiotensin converting enzyme inhibitor or a calcium channel blocker.⁵ At the end of the study the primary end point of cardiovascular mortality was not significantly different between the two groups.

Therefore, like the authors of the Syst-Eur study,⁴ we believe that the current evidence does not support the hypothesis that the use of long acting calcium channel blockers is deleterious in elderly hypertensive patients. We agree, however, that the important issue of potential differences in efficacy between antihypertensive drugs in elderly patients and patients with diabetes deserves specific attention in future large, randomised, controlled trials.

J R Cockcroft, senior lecturer. 
Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN

I B Wilkinson, senior lecturer. 
Department of Clinical Pharmacology, Addenbrooke's Hospital, Cambridge CB2 2QQ

Competing interests: None declared.