Using observational study to investigate drugs use and the risk of Parkinson’s disease: taking statin and antihypertensive medication use as an example
Date Issued
2014
Date
2014
Author(s)
Lee, Yen-Chieh
Abstract
Parkinson disease (PD) is a common neurodegenerative disorder for which causes are diverse and mostly unknown. Given that there is no mechanism-based treatment to ameliorate dopaminergic neuron loss; agents that can attenuate or modify disease processes may play a role in halting the degeneration process of PD. While using administrative databases to investigate the association of drug use and PD is increasing, concerns arise from the observational nature of the research. Without randomization, the comparison between drug users with nonusers would cause bias from confounding by indication because these two groups of population differed substantially in terms of disease severity, lifestyle factors, patterns of medical utilization, and even physicians’ perspective of their prognosis, which are all associated with the determinant of the outcome. Current literatures studying the use of chronic medications, statin and anti-hypertensive medications, and the risk of Parkinson’s disease (PD) used nonuser as comparison group and demonstrated inconsistent results. To minimize possible confounding by indication in current literature, we propose two studies that different restriction strategies are used in design to include a relatively homogeneous population. In study one, among the 43,810 statin initiators, continuation of lipophilic statins was associated with a decreased risk of PD (hazard ratio, HR:0.42, 95%C.I.:0.27–0.64) as compared with statin discontinuation. There was no association between hydrophilic statins and occurrence of PD. Long-term use of statins, either lipophilic or hydrophilic, was not significantly associated with PD. In the second study, among 65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a reduced risk of PD (aHR:0.71; 95% CI, 0.57–0.90). There was no association between the use of ACEIs (aHR = 0.80 [0.64–1.00]) or ARBs (aHR = 0.86 [0.69–1.08]) with PD. A potentially decreased association was only found for higher cumulative use of ACEIs (HR = 0.52 [0.34–0.80]) and ARBs (HR = 0.52 [0.33–0.80]). Continuation of lipophilic statin therapy was associated with a decreased incidence of PD as compared to discontinuation in statin users. Also, centrally-acting dihydropyridine CCB use and high cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD in hypertensive patients. Further long-term follow-up studies are needed to confirm the potential beneficial effects.
Subjects
statin
anti-hypertensives
Parkinson's disease
Type
thesis