RESPONSE TO NIFEDIPINE IS VARIABLE IN STABLE EXERTIONAL ANGINA

Calcium antagonists have proven useful in the treatment of angina, especially that occurring at rest. They have also

been effective in patients with stable, exertional angina, possibly because of peripheral vasodilatation with reduction in

afterload and myocardial inotropic state, coronary vasodilatation, or a combination of these mechanisms. There have,

however, been reports of nifedipine causing ischaemic cardiac pain, which could be due to an excessive fall in BP or

coronary steal decreasing local myocardial perfusion, while a rise in heart rate could increase myocardial oxygen

requirements. Animal experiments have shown that a balance exists between the benefits and potentially adverse

effects of nifedipine, which appears to be dose-related. 10 patients (7 men, 3 women, of mean age 61 years) with stable, exertional angina entered a single-blind 9-week trial

assessing the effects of different doses of nifedipine on frequency of angina and on objective indices of myocardial

ischaemia during exercise. After a 1-week run-in period, the patients received l week's treatment each with placebo;

nifedipine 10, 20, 30, 40, 30, 20, !Omg, then placebo tid. On exercise, 3 patients showed a consistent increase in the workload achieved before onset of ST segment depression,

with a decrease in the maximum precordial area of ST segment depression upon exercise during all active phases. All

3 showed maximum benefit when given nifedipine 30mg tid, but only 1 reported subjective improvement, with

reduction in frequency of angina. Four patients improved with nifedipine I Omg tid, but showed both objective and

subjective deterioration at higher doses, in 2 patients there was no improvement with any dose, and in I patient

consistent deterioration was found, the frequency of anginal attacks increasing, with objf'ctive deterioration on exercise,

at doses exceeding IOmg tid. Side effects were more common at higher doses, and included indigestion (4 patients), weakness (3), giddiness (3),

ankle swelling (3), headache (2) and flushing of hands and feet (2). Nifedipine was generally well tolerated, with 5

patients taking 120 mgfday, 4 on 90 mg/day and l on 60 mg/day. These results suggest that a dose of nifedipine which

benefits l patient with stable exertional angina, may have minimal and even adverse effects on another.

'Therefore, in both clinical practice and therapeutic trials, dose titration is fundamental

to the safe and beneficial use of nifedipine ... even when a good initial response is ob­

tained.'

Dcanticld. J. ct a!.: British Medical Journal 286: 1467 (7 May 1983)

0156-2703/83/0521-0009/0$01.00/0 "' ADIS Press INPHARMA 21 May 1983 9