Peripheral vasoconstriction induced by β‐adrenoceptor blockers: a systematic review and a network meta‐analysis

Abstract

AIMPeripheral vasoconstriction has long been described as a vascular adverse effect of β-adrenoceptor blockers. Whether β-adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to β 1 -adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta-analysis in order to assess the comparative risk of peripheral vasoconstriction of different β-adrenoceptor blockers. METHODWe searched for randomized controlled trials (RCTs) including β-adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of β-adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the β-adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374). RESULTSAmong 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with β-adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not. CONCLUSIONOur results suggest that β-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to β 1 -adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra-indications of use of β-adrenoceptor blockers and suggest that β-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease. British Journal of Clinical Pharmacology WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• β-adrenoceptor blockers are known to induce peripheral vasoconstriction, probably according to their pharmacological properties (e.g. preferential binding to β1-adrenoreceptors, intrinsic sympathomimetic activity or vasodilator effect). However, this has never been confirmed in experimental studies. WHAT THIS STUDY ADDS• Our results suggest that β-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction. Moreover, ancillary properties of β-adrenoceptor blockers widely influence this peripheral vasoconstriction: ISA and vasodilator effect are protective, whereas preferential binding to β1-adrenoreceptors does not protect from peripheral vasoconstriction.• These findings challenge FDA and French recommendations regarding precautions and contra-indications of use of β-adrenoceptor blockers, and suggest that β-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with Raynaud's phenomenon.

Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations

“…In the recent years, the use of pharmacogenomics witnessed important success in the improvement of healthcare by developing therapeutic treatment and predicting individual response [ 23 ]. Distribution of VIP variants exerts irreplaceable significance in pharmacogenomics knowledge [ 25 ].…”

“…These common polymorphisms were shown to confer a high risk towards over-anticoagulation, predisposing the individuals carrying these polymorphisms to hemorrhagic incidents [ 22 ]. In addition, a variable response to beta-blockers used in the treatment of hypertension, including propranolol [ 23 ], metoprolol, atenolol [ 24 ] and clopidogrel [ 25 , 26 ] was observed in patients of European and African origins which can trigger a stroke [ 27 , 28 ]. Other serious adverse outcomes of drugs in MetS are reported such as sudden death, bleeding events, myopathy, [ 2 , 20 , 27 , 29 ].…”

Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows

“…Furthermore, non-selective β-adrenoceptor blockers are currently used as antihypertensive, anti-tachycardia and anti-arrhythmic drugs. However, they have a variable propensity to enhance peripheral vasoconstriction [ 183 , 184 ].…”

Raynaud’s phenomenon

“…Regarding triggering/aggravating factors for RP, a recent systematic review suggested that beta-blockers differ in their tendency to exacerbate vasoconstriction and that those with intrinsic sympathomimetic activity can most likely be safely used in patients with RP. 10…”