Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport.

Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically and useful in vitro data is limited. We sought to determine whether the inhibitory effects of citalopram on platelets are mediated via its pharmacological inhibition of 5-HT transport. We quantified the inhibitory potency of (RS)-, (R)- and (S)-citalopram on platelet function. If SERT blockade is the primary mechanism for citalopram-mediated platelet inhibition, these potencies should show quantitative congruence with inhibition of 5-HT uptake. Our data show that citalopram inhibits platelet aggregation, adhesion and thromboxane production with no difference in potency between (R)- and (S)-isomers. By contrast, citalopram had a eudysmic ratio of approximately 17 (S > R) for SERT blockade. Furthermore, nanomolar concentrations of citalopram inhibited 5-HT uptake into platelets but had no effect on other platelet functions, which were inhibited by micromolar concentrations. Our data indicate that citalopram-induced inhibition of platelets in vitro is not mediated by blockade of 5-HT transport. This raises a new question for future investigation: by what mechanism(s) does citalopram inhibit platelets?

Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis.

OBJECTIVES: Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. RESULTS: Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case-control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). CONCLUSIONS: There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI.