β2‐adrenoceptor agonists and antagonists and risk of Parkinson's disease

ABSTRACT Background: β2‐adrenoreceptors have recently been identified as regulators of the α‐synuclein gene, which is implicated in the pathogenesis of Parkinson's disease. Objective: The objectives of this study were to assess the association between use of β2‐agonists and β‐antagonists and the risk of developing PD. Methods: We conducted a nested case‐control study in a cohort of 1,762,164 adults without a diagnosis of PD. They were identified on January, 1, 2004, from the electronic medical records of the largest health care provider in Israel. Participants were followed up until June 30, 2017, for the occurrence of PD. Ten randomly selected controls were matched to each case of PD on age, sex, ethnic group, and duration of follow‐up. Results: During follow‐up 11,314 patients were newly diagnosed with PD and were matched with 113,140 controls. An increased risk of PD was seen with the use of nonselective β‐antagonists (RR, 2.04 [1.90‐2.20]) but not with the use of selective β1‐antagonists (RR, 1.00 [0.95‐1.05]). Use of β2‐agonists was associated with reduced risk of PD (RR, 0.89 [0.82‐0.96] for short‐acting; RR, 0.84 [0.76‐0.93] for long‐acting; and RR, 0.49 [0.25‐0.92] for ultra‐long‐acting β2‐agonists). In an analysis of individual drugs, propranolol and salbutamol were significantly associated with PD risk, even when these drugs were ascertained 5 years prior to the index date, compared with nonusers (RR, 1.31 [1.08‐1.58] and 1.89 {1.53‐2.33]) in patients who filled <6 and ≥6 propranolol prescriptions, respectively; the corresponding RRs for salbutamol were 0.95 (0.83‐1.08) and 0.65 (0.45‐0.94), respectively. Conclusions: Use of propranolol appears to be associated with an increased risk of PD, whereas use of β2‐agonists is associated with a decreased risk of PD. © 2018 International Parkinson and Movement Disorder Society