Post Stroke Use of Selective Serotonin Reuptake Inhibitors and Clinical Outcome Among Patients With Ischemic Stroke A Nationwide Propensity Score-matched Follow-up Study
ABSTRACT BACKGROUND AND PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed after stroke. We aimed to investigate whether potential antiplatelet or vasospastic effects have important clinical implications. METHODS: Using data from Danish medical registries, we did a nationwide follow-up study among ischemic stroke patients between 2003 and 2009. We identified 5833 SSRI users, and propensity score matched these patients with nonusers in a 1:1 ratio, followed by Cox regression analysis to compute hazard ratios (HRs) of acute myocardial infarction, recurrent stroke, major bleeding, and death. RESULTS: Median follow-up time (from 30 days after discharge to death/end of follow-up) was 1159 days. In total, 2.9% had myocardial infarction, 8.1% recurrent ischemic stroke, 20.2% major bleeding, 1.4% intracranial bleeding, and 34.4% died during follow-up. SSRI users had a lower risk of the combined outcome of myocardial infarction or recurrent ischemic stroke (adjusted HR, 0.77; confidence interval [CI], 0.62-0.96). However, the SSRI users also experienced a higher risk of overall major bleeding (adjusted HR, 1.33; CI, 1.14-1.55) and a nonsignificantly higher risk of intracranial bleedings (adjusted HR, 1.14; CI, 0.62-2.12). Mortality increased in SSRI users (adjusted HR, 1.13; CI, 1.00-1.28) and death caused by bleeding increased (adjusted HR, 1.89; CI, 0.97-3.66) as compared with death by other causes (adjusted HR, 1.11; CI; 0.98-1.26). CONCLUSIONS: SSRI use after ischemic stroke was associated with a lower risk of new cardiovascular events and also with an increased bleeding risk. There was an increased mortality among SSRI users, which may be related to the increased bleeding risk.
Neurology 10/2014; DOI:10.1212/WNL.0000000000001040 · 8.30 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Acute coronary syndromes (ACS) remain life-threatening disorders, which are associated with high morbidity and mortality. Dual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in the response to clopidogrel treatment, in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y12 receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19, which affect the pharmacokinetics of clopidogrel. While the US Food and Drug Administration has issued a boxed warning for CYP2C19 poor metabolizers because of potentially reduced efficacy in these patients, results from multivariate analyses suggest that additional factors, including age, sex, obesity, concurrent diseases and drug–drug interactions, may all contribute to the overall between-subject variability in treatment response. However, the extent to which each of these factors contributes to the overall variability, and how they are interrelated, is currently unclear. The objective of this review article is to provide a comprehensive update on the different factors that influence the pharmacokinetics and pharmacodynamics of clopidogrel and how they mechanistically contribute to inter-individual differences in the response to clopidogrel treatment.Clinical Pharmacokinetics 01/2015; 54(2). DOI:10.1007/s40262-014-0230-6 · 5.49 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Introduction: There is increasing evidence for an association between treatment with selective serotonin reuptake inhibitors (SSRI) and an increased risk of bleeding events. The most important underlying mechanism appears to be inhibition of serotonin uptake in platelets, an effect that is also present in antidepressants with non-selective serotonin-reuptake inhibition (NSRI). Accordingly, also NSRI may be associated with an increased risk of bleeding. However, there is little data in this regard. Methods: Based on data (spontaneous reports of adverse drug reactions) from 2 pharmacovigilance databases (WHO-database/Vigibase(TM); BfArM/AkdÄ-database in Germany) we used a case/non-case approach and calculated reporting odds ratios (ROR) as measures for disproportionality regarding the association of treatment with an agent of the group SSRI/NSRI and haemorrhages. Results: Whereas both positive control agents (ASS and diclofenac) were statistically associated with haemorrhages in both databases (ASS: BfArM/AkdÄ, ROR 13.62 [95% CI 12.76-14.53]/WHO, ROR 12.96 [95% CI 12.75-13.16]; diclofenac: BfArM/AkdÄ, ROR 3.01 [95% CI 2.71-3.21]/WHO, ROR 2.11 [95% CI 2.05-2.16]), none of the agents of the group SSRI (ROR<1) was associated with haemorrhages. In group NSRI, only St. John's wort/hypericum was associated with haemorrhages (WHO-database, ROR 1.31 [95% CI 1.06-1.63]). Discussion: Signal detectioning in 2 pharmacovigilance databases suggest that serotonin reuptake inhibition is not associated with an increased risk of bleeding. However, underreporting may have accounted for the evaluated absent associations, particularly concerning SSRI. Regarding the detected increased risk of bleeding associated with hypericum, pharmacokinetic drug-drug interactions may be relevant independent of serotonin reuptake inhibition.Pharmacopsychiatry 11/2014; 48(01). DOI:10.1055/s-0034-1394398 · 2.17 Impact Factor