The cardiovascular effect of withdrawal of beta-adrenoceptor blocking drugs

Abstract

Some of the initial trials of β-blocking drugs in angina indicated an increase in symptoms above pretreatment levels when placebo was substituted for active drug. Later there were reports of sudden death after β-blockade withdrawal. There is evidence of increased β-receptor sensitivity, as suggested by increased responsiveness to isopre-naline after propranolol withdrawal. This is probably due to an increased β-receptor population. Other suggestions that have been considered include reversal of the reduced free triiodothyroxine, a rightward shift of the oxyhaemoglobin dissociation curve and reduced platelet aggregation, when the β-blocking drug is stopped. Further, the disease may progress during treatment, which is unmasked when treatment is withdrawn. Beta-blocking agents may differ; we have observed that in normal volunteers, withdrawal of pindolol or bopindolol, which have partial agonist properties, was not associated with a postblockade increase in response to isoprenaline. The β-blocker withdrawal syndrome is a real phenomenon, although overall the incidence is low. Besides withdrawal of the β-blocker, exertion may be a frequent prerequisite for the development of significant clinical sequelae, so exertion should be restricted when a β-blocking drug is being withdrawn. Also, the dose should be reduced gradually, particularly the final decrements.