Naomi Gronich1, Darrell R Abernethy2, Eitan Auriel3, Idit Lavi1,4, Gad Rennert1,5,6, Walid Saliba1,5. 1. Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. 2. Drug Safety Group, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA. 3. Department of Neurology, Lady Davis Carmel Medical Center, Haifa, Israel. 4. Statistics Unit, Lady Davis Carmel Medical Center, Haifa, Israel. 5. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 6. Office of Chief Physician, Clalit Health Services, Tel Aviv, Israel.
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.
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.
Authors: Francesco Giorgianni; Pierre Ernst; Sophie Dell'Aniello; Samy Suissa; Christel Renoux Journal: Am J Epidemiol Date: 2020-08-01 Impact factor: 4.897
Authors: Clive Ballard; Dag Aarsland; Jeffrey Cummings; John O'Brien; Roger Mills; Jose Luis Molinuevo; Tormod Fladby; Gareth Williams; Pat Doherty; Anne Corbett; Janet Sultana Journal: Nat Rev Neurol Date: 2020-09-16 Impact factor: 42.937