β Blockade and intermittent claudication: Placebo controlled trial of atenolol and nifedipine and their combination

Abstract

Objective - To determine the effects of the β1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication. Design - Randomised controlled double blind four way crossover trial. Setting - Royal Hallamshire Hospital, Sheffield. Subjects - 49 patients (40 men) aged 39-70 with chronic stable intermittent claudication. Interventions - Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments. Main outcome measures - Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales. Results - Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to 13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p<0·003)) and skin temperature of the more affected foot (-1·1°C; 0 to -2·2°C (p=0·05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes. Conclusions - There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to β blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication.