Yen-Chieh Lee

Discontinuation of statin therapy associates with Parkinson disease: A population-based study

Objective: To evaluate the effect of discontinuing statin therapy on incidence of Parkinson disease (PD) in statin users. Methods: Participants who were free of PD and initiated statin therapy were recruited between 2001 and 2008. We examined the association between discontinuing use of statins with different lipophilicity and the incidence of PD using the Cox regression model with time-varying statin use. Results: Among the 43,810 statin initiators, the incidence rate for PD was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of PD (hazard ratio [HR] 0.42 [95% confidence interval 0.27–0.64]) as compared with statin discontinuation, which was not modified by comorbidities or medications. There was no association between hydrophilic statins and occurrence of PD. Among lipophilic statins, a significant association was observed for simvastatin (HR 0.23 [0.07–0.73]) and atorvastatin (HR 0.33 [0.17–0.65]), especially in female users (HR 0.11 [0.02–0.80] for simvastatin; HR 0.24 [0.09–0.64] for atorvastatin). As for atorvastatin users, the beneficial effect was seen in the elderly subgroup (HR 0.42 [0.21–0.87]). However, long-term use of statins, either lipophilic or hydrophilic, was not significantly associated with PD in a dose/duration-response relation. Conclusions: Continuation of lipophilic statin therapy was associated with a decreased incidence of PD as compared to discontinuation in statin users, especially in subgroups of women and elderly. Long-term follow-up study is needed to clarify the potential beneficial role of lipophilic statins in PD.

Antihypertensive Agents and Risk of Parkinson's Disease: A Nationwide Cohort Study

Background and Purpose Hypertension has been associated with Parkinsons disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients. Methods Hypertensive patients who were free of PD, dementia and stroke were recruited from 2005–2006 using Taiwan National Health Insurance Database. We examined the association between the use of calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and the incidence of PD using beta-blockers as the reference. Cox regression model with time-varying medication use was applied. Results 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 (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.57–0.90). Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was associated with a decreased risk of PD (aHR = .69 [55–0.87]. Further decreased association was observed for higher cumulative doses of felodipine (aHR = 0.54 [0.36–0.80]) and amlodipine (aHR = 0.60 [0.45–0.79]). 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]). Conclusions Our study suggests 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 of antihypertensive agents in PD.

Comparison of the Effects of Serotonin-Norepinephrine Reuptake Inhibitors Versus Selective Serotonin Reuptake Inhibitors on Cerebrovascular Events

BACKGROUND Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased risk of intracranial hemorrhage. However, little is known about cerebrovascular risk in users of serotonin-norepinephrine reuptake inhibitors (SNRIs). Our aim was to determine the differential risk of cerebrovascular events between SSRIs and SNRIs. METHOD A nationwide population-based cohort study was conducted in adult patients who started taking SSRIs or SNRIs during the time period 2005 through 2009. The outcome of interest was defined by the first hospitalization diagnosis for ischemic stroke (ICD-9-CM codes 433, 434, 436) or intracranial hemorrhage (ICD-9-CM codes 430, 431, 432). We used a Cox regression model with time-varying medication use and adjusted for stroke risk factors to estimate the hazard ratios (HRs) of ischemic stroke and intracranial hemorrhage associated with SNRI use, using SSRI use as a reference. RESULTS Among 582,650 SSRI and 76,920 SNRI initiators with an average follow-up period of 3.2 years, there was a nonsignificantly increased trend toward intracranial hemorrhage (adjusted HR = 1.24 [95% CI, 0.97-1.58]) in SNRI users compared to SSRI users. The risk of ischemic stroke was comparable between the 2 treatment groups (adjusted HR = 1.01 [0.90-1.12]). Similar results were obtained in sensitivity analyses, considering a dose-response relation, allowance of a 7-day grace period between study drug discontinuation and outcome occurrence, and restriction to exclusive users, who remained on the initial treatment. In the subgroup analysis, there was an increased incidence of intracranial hemorrhages in SNRI users compared to SSRI users in patients without prior depression (adjusted HR = 1.63 [1.14-2.32]). CONCLUSIONS Use of SNRIs is not associated with an increased risk of either ischemic stroke or intracranial hemorrhage as compared to use of SSRIs in adult patients with depression or anxiety. However, SNRIs should be used cautiously in patients without depression.

Non-steroidal anti-inflammatory drugs use and risk of upper gastrointestinal adverse events in cirrhotic patients

The upper gastrointestinal (GI) toxicity associated with non‐steroidal anti‐inflammatory drugs (NSAID) use among cirrhotic patients remains unclear. The objective of this study was to evaluate the risk of upper GI adverse events associated with celecoxib and oral and parenteral non‐selective NSAIDs in cirrhotic patients.

Utilization of antidepressants in Taiwan: a nationwide population-based survey from 2000 to 2009

This study examined trends in antidepressant utilization in Taiwan between 2000 and 2009.

Risk of Intracranial Hemorrhage From Statin Use in Asians A Nationwide Cohort Study

Background— Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. Methods and Results— Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan’s National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94–1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11–1.67]). Conclusions— In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution.

Effects of selective serotonin reuptake inhibitors versus tricyclic antidepressants on cerebrovascular events: a nationwide population-based cohort study.

Abstract Depression is a common disorder worldwide and is strongly associated with stroke. Use of antidepressants could potentially decrease the risk of stroke in patients with depression. However, the role of selective serotonin reuptake inhibitors (SSRIs), the most frequently prescribed antidepressant in this era, in the risk of stroke showed inconsistent results. We aimed to assess the association between the use of different types of antidepressants, SSRIs and tricyclic antidepressants (TCAs), and the risk of cerebrovascular events in patients with depression or anxiety. A nationwide population-based cohort study was retrospectively conducted in patients with depression or anxiety who started to take SSRIs and TCAs identified from the Taiwan National Health Insurance claims database (2001–2009). We examined the association between the 2 types of antidepressants and incidence of stroke using a proportional hazard model adjusted for stroke risk factors. Among the 24,662 SSRI and 14,736 TCA initiators, the crude incidence rate for stroke was 10.03 and 13.77 per 100 person-years, respectively. Selective serotonin reuptake inhibitor use was not associated with risk of stroke as compared with TCAs in the time-fixed analysis. After adjusting for baseline propensity scores in the time-varying analysis, SSRI use significantly reduced risk of stroke as compared with TCAs with the adjusted hazard ratio of 0.67 (95% confidence interval, 0.47–0.96). The effect persisted even after considering the antidepressant dosage (hazard ratio, 0.65 [0.42 to 0.99]). In summary, use of SSRIs was associated with a reduced risk for stroke, as compared with TCAs, in this specific disease population.

Severe hepatic injury associated with different statins in patients with chronic liver disease: A nationwide population-based cohort study

The hepatotoxicity of statins in patients with chronic liver diseases remains unclear. In this study, we aimed to estimate the risk of severe hepatic injury associated with different statins in patients with chronic liver disease.

Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.

The objective of this nationwide retrospective cohort study was to examine the renal outcomes of HMG‐CoA reductase inhibitor (statin) initiators.

Antidepressant use and the risk of upper gastrointestinal bleeding in psychiatric patients: a nationwide cohort study in Taiwan.

Abstract The magnitude of risk between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding (UGIB) is still unknown in patients with psychiatric diseases. The aim of this study was to quantify the risk of UGIB induced by use of antidepressants with different affinities for serotonin transporters in psychiatric patients using Taiwan’s nationwide health insurance claims database. We conducted a propensity score- matched retrospective cohort study and identified 304,606 psychiatric patients who initiated antidepressant treatment during the 2005–2006 period. Antidepressants were classified as high- (HA group), intermediate- (IA group), or low-affinity (LA group) serotonin reuptake inhibitors. Patients in the LA group were matched 1:1 to those in the HA and IA groups according to their propensity scores. Subjects who were successfully matched were followed up from the date of antidepressant initiation to first hospitalization for UGIB, drug discontinuation, transition to or addition of antidepressants in another group, or the study’s end (whichever occurred first). A total of 153,486 psychiatric patients were successfully matched, and 498 first UGIB events were identified. Compared with the LA group, patients in the HA group had a higher risk for UGIB (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.11–1.71). The HR (95% CI) of the IA group was 1.11 (95% CI, 0.88–1.41). The trend for elevated UGIB risk with increasing affinity of serotonin transporters was statistically significant (P < 0.01). Elderly patients and those with prior UGIB history were more susceptible to the harmful effects. Our findings suggest that the use of high-affinity serotonin reuptake inhibitors may increase the risk for UGIB in psychiatric patients.