title: Peripheral vasoconstriction induced by β-adrenoceptor blockers: a systematic review and a network meta-analysis.
abstract: Peripheral 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 β1 -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.
  
  
  
  We 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).
  
  
  
  Among 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.
  
  
  
  Our results suggest that β-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to β1 -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.
authors.affiliation: Pôle Santé Publique Pharmacovigilance, Grenoble University Hospital (CHU Grenoble-Alpes), F-38000, Grenoble, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Khouri
authors.affiliation: Pôle Recherche, Pharmacologie Clinique, INSERM CIC1406, Grenoble University Hospital (CHU Grenoble-Alpes), F-38000, Grenoble, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouve
authors.affiliation: Univ. Grenoble Alpes HP2, F-38000, Grenoble, France.|INSERM, HP2, F-38000, Grenoble, France.|Grenoble University Hospital (CHU Grenoble-Alpes), Clinique de Médecine Vasculaire, F-38000, Grenoble, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Blaise
authors.affiliation: Grenoble University Hospital (CHU Grenoble-Alpes), Clinique de Médecine Vasculaire, F-38000, Grenoble, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Carpentier
authors.affiliation: Pôle Recherche, Pharmacologie Clinique, INSERM CIC1406, Grenoble University Hospital (CHU Grenoble-Alpes), F-38000, Grenoble, France.|Univ. Grenoble Alpes HP2, F-38000, Grenoble, France.|INSERM, HP2, F-38000, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Cracowski
authors.affiliation: Pôle Recherche, Pharmacologie Clinique, INSERM CIC1406, Grenoble University Hospital (CHU Grenoble-Alpes), F-38000, Grenoble, France.|Univ. Grenoble Alpes HP2, F-38000, Grenoble, France.|INSERM, HP2, F-38000, Grenoble, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Roustit
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013566:Sympathomimetics / Q000008:administration & dosage / Q000009:adverse effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D013566:Sympathomimetics
keywords: Raynaud's phenomenon; peripheral vasoconstriction; β-adrenoceptor blockers