Effects of Strong P2Y12 Receptor Inhibition by Prasugrel on Platelet Inhibition During Endotoxemia: A Randomized Controlled Trial

Abstract Abstract 1245 Background: P2Y12 receptor antagonists have become a mainstay for the treatment of cardiovascular diseases. Yet, they have rarely been evaluated under pathophysiological conditions apart from arterial diseases. Objectives: We hypothesized interactions between prasugrel and enhanced von Willebrand Factor (VWF) release in a model of systemic inflammation, and compared the pharmacodynamic effects of prasugrel versus placebo on agonist-induced platelet aggregation and shear-induced platelet plug formation. Subjects/Methods: Twenty healthy male volunteers were enrolled in a double-blind, placebo-controlled two-way cross-over trial. Each volunteer received either placebo or a 60 mg-loading dose of prasugrel two hours before endotoxin infusion. Platelet inhibition was measured with Multiple Electrode Aggregometry (MEA), the Platelet Function Analyzer-100 (PFA-100) and the Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, respectively. Results: Prasugrel reduced the platelet reactivity index in the VASP assay from 79% to 5–7%, and unequivocally prolonged the closure times of the Innovance cartridge to >300s, but also the CADP-CT to >300s in the majority of subjects. Prasugrel not only blunted platelet aggregation induced by ADP (−81%), but also other pathways including arachidonic acid (−60%), ristocetin (−75%; p<0.001 for all), and to a lesser degree collagen or thrombin receptor activating peptide (TRAP). Prasugrel decreased shear-induced platelet plug formation but VWF release during endotoxemia partly antagonized the inhibitory effect of prasugrel as measured with the PFA-100. Endotoxemia acutely decreased ristocetin and TRAP induced platelet aggregation, and enhanced ristocetin induced aggregation after 24h. Conclusions: These data for the first time demonstrate that strong in vivo blockade of P2Y12 by prasugrel inhibits a broad spectrum of platelet aggregation pathways. However, VWF release may reduce prasugrel's effects under high shear conditions. Disclosures: No relevant conflicts of interest to declare.

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Effects of prasugrel on platelet inhibition during systemic endotoxaemia: a randomized controlled trial

Clinical Science ◽

10.1042/cs20120194 ◽

2012 ◽

Vol 123 (10) ◽

pp. 591-600 ◽

Cited By ~ 21

Author(s):

Alexander O. Spiel ◽

Ulla Derhaschnig ◽

Michael Schwameis ◽

Johann Bartko ◽

Jolanta M. Siller-Matula ◽

...

Keyword(s):

Platelet Aggregation ◽

Controlled Trial ◽

Platelet Inhibition ◽

Inhibitory Effect ◽

Double Blind ◽

Multiple Electrode Aggregometry ◽

Von Willebrand ◽

Plug Formation ◽

Induced Aggregation

P2Y12 receptor antagonists have become a mainstay for the treatment of CVD (cardiovascular diseases). However, they have rarely been evaluated under pathophysiological conditions apart from arterial diseases. We hypothesized interactions between prasugrel and enhanced vWF (von Willebrand Factor) release in a model of systemic inflammation, and compared the pharmacodynamic effects of prasugrel against placebo on agonist-induced platelet aggregation and shear-induced platelet plug formation. A total of 20 healthy male volunteers were enrolled in a double-blind placebo-controlled two-way crossover trial. Each volunteer received either placebo or a 60 mg loading dose of prasugrel 2 h before endotoxin or placebo infusion. Platelet inhibition was measured with MEA (multiple electrode aggregometry), the PFA-100 system and the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay. Prasugrel blunted various platelet aggregation pathways, including those induced by ADP (−81%), AA (arachidonic acid) (−60%), ristocetin (−75%; P<0.001 for all) and, to a lesser degree, collagen or TRAP (thrombin-receptor-activating peptide). Prasugrel decreased shear-induced platelet plug formation, but vWF release during endotoxaemia partly antagonized the inhibitory effect of prasugrel as measured with the PFA-100 system. Endotoxaemia acutely decreased ristocetin and TRAP-induced platelet aggregation, and enhanced ristocetin-induced aggregation after 24 h. Strong in vivo blockade of P2Y12 inhibits a broad spectrum of platelet aggregation pathways. However, vWF release may reduce prasugrel's effects under high-shear conditions.

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A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry

Thrombosis and Haemostasis ◽

10.1160/th07-09-0555 ◽

2008 ◽

Vol 99 (01) ◽

pp. 215-222 ◽

Cited By ~ 58

Author(s):

Christopher D Payne ◽

Ying G Li ◽

Nagy A Farid ◽

John T Brandt ◽

David S Small ◽

...

Keyword(s):

Platelet Aggregation ◽

Light Transmission ◽

Platelet Reactivity ◽

Platelet Inhibition ◽

P2y12 Receptor ◽

Reactivity Index ◽

High Dose ◽

Receptor Blockade ◽

Vasp Phosphorylation ◽

Light Transmission Aggregometry

SummaryPlatelet inhibition as measured by vasodilator-stimulated phosphoprotein (VASP) and light transmission aggregometry (LTA) have shown concordance following dosing of clopidogrel. No reports have directly compared theVASP assay and LTA at the levels of P2Y12 blockade after loading doses (LDs) of prasugrel or high dose clopidogrel (600 and 900 mg).The aim was to compare theVASP assay and LTA during the loading dose phase of a comparative study of prasugrel and clopidogrel. Prasugrel 60 mg LD/10 mg maintenance dose (MD) and clopidogrel 300 mg/75 mg and 600 mg/75 mg LD/MD regimens were compared in a 3-way crossover study in 41 healthy, aspirin-free subjects. Each LD was followed by seven daily MDs and a 14-day washout period. P2Y12 receptor blockade was estimated using theVASP assay, expressed as platelet reactivity index (VASP-PRI). Platelet aggregation was assessed by light transmission aggregometry (20 and 5 μM ADP).Twenty-four hoursafter prasgurel 60 mg or clopidogrel 300 mg and 600 mg, respectively, VASP-PRI decreased from ∼80% to 8.9%, 54.7%, and 39.0 %, and maximal platelet aggregation (MPA) decreased from ∼79% to 10.8%, 42.7%, and 31.2%, with an overall VASP:MPA correlation of 0.88 (p<0.01). VASP assay responses after the clopidogrel LDs showed a wider range of values (300 mg: 0–93%; 600 mg: 0–80%) than prasugrel (0–13%); MPA responses followed a similar trend. Pearson’s correlation suggested a strong agreement between VASP and LTA (20 μM ADP) for MPA (r=0.86, p<0.0001).VASP and LTA demonstrated concordance across the response range of P2Y12 receptor blockade following thienopyridine LDs.

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Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel In Patients with Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

Blood ◽

10.1182/blood.v116.21.3322.3322 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3322-3322

Author(s):

In-Suk Kim ◽

Young-Hoon Jeong ◽

Arum Kim ◽

Gyeong-Won Lee

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Platelet Aggregation ◽

Maintenance Dose ◽

Conflicts Of Interest ◽

Platelet Reactivity ◽

Platelet Inhibition ◽

Cyp2c19 Genotype ◽

Loss Of Function

Abstract Abstract 3322 Objectives The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to CYP2C19 genotype. Background Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can overcome the loss-of-function effect of CYP2C19 variants. Methods We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150-mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow, platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (Aggmax). High post-treatment platelet reactivity (HPPR) was defined as 5 μmol/l ADP-induced Aggmax > 50%. Results In non-carriers, the two groups did not differ with respect to changes in platelet measures, and could achieve fewer rates of HPPR at 30-day follow-up (< 5%). In carriers, changes in 5 and 20 μmol/l ADP-induced Aggmax were significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple vs. high-MD group. Fewer patients in the triple group met the criteria of HPPR at 30-day follow-up compared with the high-MD group (2.6% vs. 21.1%, p = 0.014). Conclusions Among AMI patients with CYP2C19 variants, adjunctive cilostazol enhances platelet inhibition and reduces the rate of HPPR, as compared with high-MD clopidogrel. (Adjunctive Cilostazol Versus High-MD ClopidogrEL in Patients With Acute Myocardial Infarction According to CYP2C19 genotype [ACCEL-AMI-CYP2C19]; NCT00915733). Disclosures: No relevant conflicts of interest to declare.

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Head-to-Head Comparison of Consensus-Recommended Platelet Function Tests to Assess P2Y12 Inhibition—Insights for Multi-Center Trials

Journal of Clinical Medicine ◽

10.3390/jcm9020332 ◽

2020 ◽

Vol 9 (2) ◽

pp. 332

Author(s):

Jean-Christophe Bélanger ◽

Fabio Luiz Bandeira Ferreira ◽

Mélanie Welman ◽

Rahma Boulahya ◽

Jean-François Tanguay ◽

...

Keyword(s):

Flow Cytometry ◽

Platelet Aggregation ◽

Platelet Function ◽

Platelet Reactivity ◽

Receptor Activation ◽

P2y12 Receptor ◽

Reactivity Index ◽

Specific Method ◽

Vasp Phosphorylation ◽

Receptor Inhibitor

The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation level is a highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently, a simple ELISA kit has been commercialized. The primary objective of this study was to compare the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet aggregation testing by Multiplate® whole-blood aggregometry. Blood from 24 healthy volunteers was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR-C 66096). Platelet function testing was carried out simultaneously by Multiplate® aggregometry and by VASP assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12 receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor activation across the modalities. Platelet reactivity index values of both ELISA- and flow cytometry-based VASP assessment methods correlated strongly (r = 0.87, p < 0.0001) and showed minimal bias (1.05%). Correlation with Multiplate® was slightly higher for the flow cytometry-based VASP assay (r = 0.79, p < 0.0001) than for the ELISA-based assay (r = 0.69, p < 0.0001). Intraclass correlation (ICC) was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between 0.86 and 0.92). In conclusion, the consensus-recommended assays with their standardized cut-offs should not be used interchangeably in multi-center clinical studies but, rather, they should be standardized throughout sites.

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Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660138 ◽

1985 ◽

Vol 54 (04) ◽

pp. 808-812 ◽

Cited By ~ 7

Author(s):

Ulf Berglund ◽

Henning von Schenck ◽

Lars Wallentin

Keyword(s):

Platelet Aggregation ◽

Angina Pectoris ◽

Platelet Function ◽

Plasma Levels ◽

Platelet Reactivity ◽

Inhibitory Effect ◽

Controlled Study ◽

Double Blind ◽

Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

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Multiple electrode aggregometry: A new device to measure platelet aggregation in whole blood

Thrombosis and Haemostasis ◽

10.1160/th06-05-0242 ◽

2006 ◽

Vol 96 (12) ◽

pp. 781-788 ◽

Cited By ~ 288

Author(s):

Andreas Calatzis ◽

Sandra Penz ◽

Hajna Losonczy ◽

Wolfgang Siess ◽

Orsolya Tóth

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Blood Platelet ◽

Platelet Inhibition ◽

New Device ◽

Platelet Aggregometry ◽

Spontaneous Platelet Aggregation ◽

Induced Aggregation ◽

Blood Platelet Aggregation ◽

Multiple Electrode

SummarySeveral methods are used to analyse platelet function in whole blood. A new device to measure whole blood platelet aggregation has been developed, called multiple electrode platelet aggregometry (MEA). Our aim was to evaluate MEA in comparison with the single platelet counting (SPC) method for the measurement of platelet aggregation and platelet inhibition by aspirin or apyrase in diluted whole blood. Platelet aggregation induced by different concentrations of ADP, collagen and TRAP-6 and platelet inhibition by apyrase or aspirin were determined in citrateor hirudin-anticoagulated blood by MEA and SPC. MEA indicated that spontaneous platelet aggregation was lower, and stimulated platelet aggregation was higher in hirudin- than citrate-anticoagulated blood. In hirudin-anticoagulated, but not citrate-anticoagulated blood, spontaneous platelet aggregation measured by MEA was inhibited by apyrase. For MEA compared with SPC the dose response-curves of agonist-induced platelet aggregation in citrate- and hirudin-blood showed similar EC50 values for TRAP, and higher EC50 values for ADP (non-significant) and collagen (p<0.05). MEA and the SPC method gave similar results concerning platelet-inhibition by apyrase and aspirin. MEA was more sensitive than SPC to the inhibitory effect of aspirin in collagen-induced aggregation. In conclusion, MEA is an easy, reproducible and sensitive method for measuring spontaneous and stimulated platelet aggregation, and evaluating antiplatelet drugs in diluted whole blood. The use of hirudin as an anticoagulant is preferable to the use of citrate. MEA is a promising technique for experimental and clinical applications.

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Comparison of VASP-phosphorylation assay to light-transmission aggregometry in assessing inhibition of the platelet ADP P2Y12 receptor

Thrombosis and Haemostasis ◽

10.1160/th06-09-0491 ◽

2006 ◽

Vol 96 (12) ◽

pp. 767-773 ◽

Cited By ~ 29

Author(s):

Agnieszka Pampuch ◽

Giovanni de Gaetano ◽

Chiara Cerletti

Keyword(s):

Light Transmission ◽

Platelet Reactivity ◽

Flow Cytometric Analysis ◽

Individual Variability ◽

P2y12 Receptor ◽

Reactivity Index ◽

Drug Induced ◽

Light Transmission Aggregometry ◽

Adp Receptor

SummaryThere is need to improve platelet function testing to monitor the response to antiplatelet drugs. We compared flow-cytometric analysis of intraplatelet vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) to light-transmission aggregometry for the detection of drug-induced in-vitro inhibition of the platelet P2Y12 ADP receptor on 22 healthy subjects (10 males, 12 females, 28.5 ± 6.6 years). The platelet reactivity index (PRI) of VASP was calculated both from mean fluorescence intensity (MFI) and percent of fluorescence-positive platelets in the presence of PGE1 with or without ADP (10 µM). Platelet aggregation was induced by ADP (1.25, 2.5 and 5 µM). Cangrelor, a competitive inhibitor of the P2Y12 receptor, preincubated 5 minutes, induced a concentration-dependent inhibition of platelet ADP-receptor function in both tests. Indeed PRI (%) based on either MFI or percent platelets gated were highly correlated with each other (r = 0.97, p<0.0001) and with aggregation in- duced by ADP. The IC50 of cangrelor against each of the three ADP concentrations used in aggregometry increased from 5.8 ± 3.4 nM to 23.1 ± 4.0 nM and to 98 ± 25 nM, respectively. The IC50 of cangrelor based on VASP-P was within the same range (25.5 ± 7.7 nM). No correlation was observed between IC50 values of cangrelor and ADP concentrations giving 50% effect (EC50) in the absence of the drug. However, at 10 nM cangrelor seven subjects could be identified by the VASP-P assay as “low responders” to the drug (PRI> 50%), and six of them also had an aggregation response to 5 µM ADP > 50%. These six subjects showed the lowest ADP EC50 values in the absence of the drug, possibly reflecting high sensitivity of their platelet P2Y12 receptors to ADP. In conclusion, both the VASP-P assay and light-transmission aggregometry detect in a comparable way in-vitro pharmacological inhibition of the platelet P2Y12 ADP receptor and its individual variability.

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INITIAL STUDIES IN MAN WITH A NOVEL THROMBOXANE RECEPTOR BLOCKING DRUG GR32191

10.1055/s-0038-1643467 ◽

1987 ◽

Author(s):

M Thomas ◽

P Lumley ◽

P Ballard ◽

J R O'Brien

Keyword(s):

Platelet Aggregation ◽

Bleeding Time ◽

Ex Vivo ◽

Plasma Concentrations ◽

Blocking Drug ◽

Double Blind ◽

Receptor Blocking ◽

Thromboxane Receptor ◽

Pre Treatment ◽

Induced Aggregation

In-vitro GR32191 is a potent and specific thromboxane receptor blocking drug on platelets, and vascular and airways smooth muscle (Lumley et al this meeting). We have undertaken studies in healthy male subjects (n) to examine the effects of oral GR32191 upon platelet aggregation ex-vivo and template bleeding time. Platelet aggregation was monitored in whole blood by counting platelets electronically. Concentration-effect curves to U-46619 and ADP were constructed prior to and following drug or placebo. The degree of rightward displacement of a curve due to treatment was expressed as a concentration-ratio (CR) which was calculated at the 50% aggregation level (ECso post-treatment ECso pre-treatment). Plasma concentrations of GR32191 were determined by h.p.l.c. After single doses of GR32191 mean peak CR's of 8 and 80 were achieved with 0.125 and 0.25mg/kg (n=4) and values of 74 and 234 with 0.5 and lmg/kg (n=4). Peak effects were seen within 2 hours of dosing while activity was still present between 8 and 24 hours. ADP-induced aggregation was unaffected by drug (CR<2) and placebo was without significant effect upon the sensitivity to either aggregating agent (CR<2). GR32191 was rapidly absorbed and the plasma elimination half-life was about 2 hours. GR32191 17.5mg 12-hourly for 10 days (n=6) produced a progressive antagonism of U-46619 induced aggregation which resulted in a large continuous blockade in all subjects (range of 12htrough CR's 85 to 287). However, plasma concentrations of GR32191 did not accumulate on repeated administration. In a double-blind, placebo-controlled, cross-over study (n=16), a statistically significant (p= 0.002) increase in bleeding time was seen following treatment with GR32191 40mg twice daily for 7 days (pre-treatment mean 3.79 min, post-placebo mean 3.47 min, post-GR32191 mean 5.42 min). Rectal bleeding (n=l) has occurred with GR32191 but otherwise tolerability has been good. No drug related changes have been seen in routine laboratory safety screens. Clinical studies are in progress.

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Early determination of clopidogrel responsiveness by platelet reactivity index identifies patients at risk for cardiovascular events after myocardial infarction

Thrombosis and Haemostasis ◽

10.1160/th11-01-0022 ◽

2011 ◽

Vol 106 (07) ◽

pp. 141-148 ◽

Cited By ~ 10

Author(s):

Andreas Schäfer ◽

Ulrike Flierl ◽

Jürgen Kössler ◽

Nora Seydelmann ◽

Anna Kobsar ◽

...

Keyword(s):

Myocardial Infarction ◽

Platelet Reactivity ◽

Density Lipoprotein ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Systematic Evaluation ◽

Reactivity Index ◽

Operating Characteristics ◽

Patients At Risk ◽

Acute Mi

SummaryWhile acute myocardial infarction (MI) is associated with impaired clopidogrel responsiveness, systematic evaluation is lacking due to the inability of functional aggregation-based assays to analyse clopidogrel responsiveness in the presence of glycoprotein IIb/IIIa inhibitors. Using the P2Y12-specific, non-aggregation-based platelet-reactivity-index (PRI) we assessed clopidogrel responsiveness in patients with acute MI. Clopidogrel responsiveness was determined 24 hours (h) after loading with 600 mg clopidogrel in 54 patients with acute MI admitted for coronary intervention. A PRI > 50% was considered as suboptimal inhibition. Overall response in MI patients was suboptimal with a median PRI of 58%. Diabetes, low high-density lipoprotein and pre-hospital clopidogrel loading were associated with impaired clopidogrel responsiveness. Patients loaded at first medical contact had a significantly weaker platelet inhibition by clopidogrel after 24 h (PRI 63%) compared to those loaded peri-interventionally (PRI 54%, p=0.014). Clinical outcome was assessed as a combination of cardiac death, non-fatal MI, stent thrombosis, ischaemic stroke, and urgent target vessel revascularisation after 12 months. The pre-selected cut-off of PRI ≤ 50% yielded a sensitivity of 87% at a specificity of 26%, whereas a PRI ≤ 57% determined by receiver-operating characteristics (ROC)-analysis yielded a sensitivity of 80% at a specificity of 56% (event rate: PRI ≤ 57%: 12.0%; PRI > 57%: 41.4%, p=0.0136). In conclusion, PRI detects clopidogrel responsiveness in acute MI patients requiring glycoprotein IIb/IIIa antagonism; and impaired clopidogrel responsiveness predisposes to clinical events. Pre-hospital clopidogrel loading was associated with impaired response and more adverse events challenging the concept of earliest oral clopidogrel loading in MI patients.

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Antiplatelet effects of citalopram in patients with ischaemic stroke: A randomized, placebo-controlled, double-blind study

Scientific Reports ◽

10.1038/s41598-019-56487-8 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Kristian Lundsgaard Kraglund ◽

Janne Kaergaard Mortensen ◽

Søren Paaske Johnsen ◽

Grethe Andersen ◽

Erik Lerkevang Grove

Keyword(s):

Platelet Aggregation ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Platelet Reactivity ◽

Significant Inhibition ◽

Controlled Study ◽

Double Blind Study ◽

Stroke Patients ◽

Double Blind ◽

Ssri Treatment

AbstractWe evaluated the effect of SSRI treatment on platelet aggregation in patients with ischaemic stroke and included patients from the randomized double-blind controlled study of citalopram in acute ischaemic stroke (TALOS). Patients on clopidogrel were included 6 months after acute ischaemic stroke. Platelet parameters, including P2Y12 platelet reactivity using the VerifyNow System, were measured at the last day of study treatment and repeated after a 14-day wash-out period. A total of 60 patients were included (n = 32 randomized to citalopram). Platelet aggregation levels did not differ between the citalopram group (mean 116, 95% CI 89 to 143) and the placebo group (mean 136, 95% CI 109 to 163) (On-treatment, p = 0.14). Similarly, there was no significant change in platelet aggregation in the citalopram group from on-treatment to post-treatment (mean difference 2.0; 95% CI −18 to 14). Platelet count, size and turnover were not affected by SSRI treatment. In conclusion, SSRI therapy did not lead to statistically significant inhibition of platelet aggregation in ischaemic stroke patients treated with clopidogrel.

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