ABRUPT PROPRANOLOL WITHDRAWAL IN ANGINA-PECTORIS - EFFECTS ON PLATELET-AGGREGATION AND EXERCISE TOLERANCE

Data collected before the initial reports of myocardial infarction following sudden withdrawal of propranolol are presented here to evaluate possible mechanisms for this phenomenon. Twenty patients with angina pectoris were randomized into placebo and propranolol (160 mg./day) treated groups and followed for 50 weeks at which time treatment was abruptly discontinued. Measurements of exercise tolerance, the product of heart rate and blood pressure at exercise end-point (HR × BP), and platelet aggregation thresholds in response to ADP and epinephrine were made before, during, and after treatment. Prior to propranolol, mean total work performance was 765 ± 125 k.p.m., HR × BP (heart rate-blood pressure product) was 16,800 ± 1,535. Mean platelet aggregation threshold with ADP was 1.32 μM* * Geometric mean.; with epinephrine 1.26 μM*. Patients treated with propranolol demonstrated significant improvement in exercise performance (1,790 ± 285 k.p.m., p < .01), reduction in HR × BP (12,000 ± 895, p < .01), and an elevation in platelet aggregation threshold; with ADP 3.43 μM* (p < .01); with epinephrine 12.9 μM* (p < .01). Following abrupt cessation of propranolol, exercise tolerance and HR × BP fell below pretreatment levels (630 ± 117 k.p.m. and 15,500 ± 513, respectively). Similarly platelet aggregation threshold fell to 1.0 μM* with ADP and 0.57 μM* with epinephrine. In six patients platelets were significantly more hyperaggregable than prior to therapy. Anginal frequency increased in all, but no acute infarction was observed. Abrupt withdrawal of propranolol may be deleterious in patients, sometimes causing rebound" platelet hyperaggregability associated with increasing anginal frequency and decreasing exercise tolerance. © 1978."