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

Effects of β2‐Adrenergic Agonists on Risk of Parkinson's Disease in COPD: A Population‐Based Study

“…Their results were consistent when the latency period was extended to five and 8 years. However, their findings should be interpreted with caution because comparisons were made across multiple drugs (n=>10), which might inflate the false‐positive rate 13 . Moreover, neither study considered the competing risk of death.…”

“…Of note, their study only examined salbutamol use and only adjusted for age, sex and education 6 . A more rigorous, nested case‐control study found that the 2‐year PD risk was reduced by 11% to 51% for use of various types of β 2 ‐agonists in a large healthcare institute in Israel, controlling for rurality, major chronic conditions, smoking, alcohol consumption and the use of various cardiovascular drugs 13 . Their results were consistent when the latency period was extended to five and 8 years.…”

“…Understanding the potential add‐on effects of β 2 ‐agonists on PD will improve its profile in treating COPD. Large‐scale epidemiological studies show that β 2 ‐adrenoreceptor agonists are associated with a decreased risk of PD in the general population 6,13 . However, to the best of our knowledge, it remains unclear whether or not the use of β 2 ‐agonists affects the risk of PD in patients who are diagnosed with COPD, and if so, to what extent.…”

From beta‐blockers to Parkinson's disease in respect of essential tremor

“…We read with great interest the study of the association between β2‐adrenoceptor agonist and antagonist exposure and the risk of Parkinson's disease (PD), by Gronich and colleagues . The good news is that beta‐receptor agonists might be protective for PD; however, neurologists will be worried by data that suggest exposure to nonselective β2‐adrenoceptor antagonists, particularly propranolol, increases the risk for PD by 2.6 times.…”

Adrenoceptor agonists and antagonists and risk of Parkinson's disease

“…We read with great interest the article by Gronich and colleagues on the effects of β2‐adrenoceptor agonists and antagonists on the risk of Parkinson's disease (PD). This case‐nested study in a large population of adults without PD followed for over 13 years showed that 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.…”