The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes

2018 ◽  
Vol 33 (3) ◽  
pp. 109-118 ◽  
Author(s):  
Karin B. Mirzaev ◽  
Eric Rytkin ◽  
Kristina A. Ryzhikova ◽  
Elena A. Grishina ◽  
Zhannet A. Sozaeva ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Antiplatelet Therapy ◽  
Early Phase ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Categorical Variables ◽  
P Value ◽  
Coronary Syndrome ◽  
Significant Difference

Abstract Background The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Methods Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Results Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19*2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19*1/*1 than those in CYP2C19*1/*2+CYP2C19*2/*2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19*2 (OR: 4.365, CI: 1.25–17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002–0.229, p=0.049). The remaining polymorphisms had no influence. Conclusions The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.

scholarly journals Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

2021 ◽  
Author(s):  
Suvro Sankha Datta ◽  
Dibyendu De ◽  
Nadeem Afroz Muslim
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P Value ◽  
Platelet Response ◽  
Percutaneous Coronary ◽  
The Individual ◽  
Platelet Functions

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine disdiphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

scholarly journals Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

2021 ◽  
Vol 5 (02) ◽  
pp. 108-113
Author(s):  
Suvro Sankha Datta ◽  
Dibyendu De ◽  
Nadeem Afroz Muslim
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P Value ◽  
Platelet Response ◽  
Percutaneous Coronary ◽  
The Individual

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine diphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

2013 ◽  
Vol 110 (12) ◽  
pp. 1223-1231 ◽  
Author(s):  
Dominick J. Angiolillo ◽  
Jose L. Ferreiro ◽  
Joseph A. Jakubowski ◽  
Kenneth J. Winters ◽  
Mark B. Effron ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Active Metabolite ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Coronary Syndrome ◽  
Metabolite Generation ◽  
Artery Disease ◽  
The Impact

SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

scholarly journals Modern Antiplatelet Therapy for Percutaneous Coronary Intervention. How to Make the Right Choice?

2020 ◽  
Vol 16 (6) ◽  
pp. 1017-1023
Author(s):  
T. M. Uskach ◽  
A. S. Tereshchenko
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Invasive Treatment ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment ◽  
Percutaneous Coronary

Dual antiplatelet therapy is the most important step in acute coronary syndrome (ACS) treatment. The new generation of inhibitors of P2Y12 platelet receptors (prasugrel and ticagrelor) provide more pronounced platelet inhibition than clopidogrel. The drugs differ in pharmacodynamics and platelet reactivity tests due to different mechanisms of binding to P2Y12 receptors. The antiplatelet effect of prasugrel and ticagrelor provides clinical benefit and better prognosis in patients with various forms of ACS. In patients with ST-segment elevation ACS prasugrel and ticagrelor are preferred over clopi-dogrel due to their higher efficacy and better clinical outcomes, and currently have preferential positions in guidelines compared to clopidogrel. The comparison of prasugrel versus ticagrelor (ISAR-REACT 5 trial) demonstrated superiority of prasugrel over ticagrelor in patients with ST-segment elevation ACS, for whom an invasive evaluation is planned and in early invasive treatment non-ST-segment elevation ACS. The choice of a drug for dual antiplatelet therapy in various clinical situations remains controversial. The latest ESC guidelines on non-ST elevation ACS (2020) [1] demonstrate the possible preference for prasugrel in patients with ACS without ST-segment elevation undergoing percutaneous coronary intervention. Current article demonstrates the results of recent clinical studies and the real clinical data regarding antiplatelet therapy in patients with coronary interventions. The indications for the use of P2Y12 platelet inhibitors in certain groups of patients are outlined. Treatment selection of the most effective and safe drugs in patients with ACS is highlighted according to the updated European guidelines.

Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome

2013 ◽  
Vol 33 (01) ◽  
pp. 9-15 ◽  
Author(s):  
M. Orban ◽  
S. Massberg ◽  
D. Sibbing
Keyword(s):  
Acute Coronary Syndrome ◽  
Large Scale ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Onset Of Action ◽  
Thrombotic Risk ◽  
Coronary Syndrome

SummaryBlood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent anti platelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new anti platelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study

2019 ◽  
Vol 119 (04) ◽  
pp. 660-667 ◽  
Author(s):  
Matthias Freynhofer ◽  
Ralph Hein-Rothweiler ◽  
Paul Haller ◽  
Daniel Aradi ◽  
Döme Dézsi ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Early Morning ◽  
Platelet Inhibition ◽  
Control Group ◽  
Diurnal Variability ◽  
Coronary Syndrome ◽  
Adp Receptor

AbstractLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

scholarly journals Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

2017 ◽  
Vol 24 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Peng Ding ◽  
Yujie Wei ◽  
Nana Chen ◽  
Huiliang Liu
Keyword(s):  
Acute Coronary Syndrome ◽  
Healthy Volunteers ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

scholarly journals Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients Presenting with Acute Coronary Syndrome and Cardiogenic Shock – a Case Series

2017 ◽  
Vol 42 (4) ◽  
pp. 1336-1341 ◽  
Author(s):  
Michal Droppa ◽  
Oliver Borst ◽  
Dominik Rath ◽  
Karin Müller ◽  
Meinrad Gawaz ◽  
...  
Keyword(s):  
Cardiogenic Shock ◽  
Platelet Reactivity ◽  
Case Series ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Cardiac Events ◽  
Coronary Syndrome ◽  
Multiple Electrode Aggregometry ◽  
Single Center Experience

Background/Aims: Patients with acute coronary syndromes (ACS) presenting with cardiogenic shock (CS) are at particular risk for death and adverse cardiac events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to decreased organ hypoperfusion or hypothermia and challenges regarding oral administration contribute to this risk. We report a single center experience regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients with CS treated with percutaneous coronary intervention (PCI). Methods: Twelve patients with ACS and CS undergoing PCI, not pretreated with oral P2Y12-receptor inhibitors, were treated with cangrelor. Platelet inhibition was assessed by multiple electrode aggregometry (MEA) before and after PCI, immediately and 2 hours after stopping the cangrelor infusion. Results: Nine patients recovered from their cardiogenic shock, 3 patients died. Platelet reactivity decreased from 65.9 (SD 41.0) U before PCI to 15.8 (SD 10.8) U after PCI, 13.4 (SD 7.7) U at the end of infusion and 33.8 (SD 19.9) 2 hours after stopping the cangrelor infusion. There was no non-responder under cangrelor infusion (MEA < 46 U). Conclusions: Due to its favorable PK/PD profile, cangrelor overcomes problems with reduced absorption and effects of oral P2Y12-receptor inhibitors and should be considered for periprocedural treatment of patients with CS.

Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events

2014 ◽  
Vol 112 (09) ◽  
pp. 551-557 ◽  
Author(s):  
Katerina Stavrou ◽  
Ioanna Koniari ◽  
Vassilios Gkizas ◽  
Angelos Perperis ◽  
Kosmas Kontoprias ◽  
...  
Keyword(s):  
Propensity Score ◽  
Platelet Reactivity ◽  
Academic Research ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Bleeding Events ◽  
Clinical Trial Registration ◽  
Propensity Score Model ◽  
Coronary Syndrome

SummaryPlatelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58–0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3–37.3 vs 84.6, 95% CI 73.6–95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01774955.

Abstract 13003: Efficacy of Cilostazol on Platelet Reactivity and Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention: Insights From a Meta-Analysis of Randomized Trials

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Bora Toklu ◽  
Amita Singh ◽  
Frederick Feit ◽  
Sripal Bangalore
Keyword(s):  
Antiplatelet Therapy ◽  
Stent Thrombosis ◽  
Randomized Trials ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Percutaneous Coronary ◽  
Drug Eluting ◽  
Secondary Outcomes

Introduction: Cilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduce adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined. Methods: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and target vessel revascularization (TVR) as well as safety outcomes of bleeding and drug discontinuations. Results: In 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73units lower with TAPT vs. DAPT (95% CI -61.41 to -34.04, P <0.0001; mean PRU 182.90 vs. 232.65). TAPT also reduced platelet inhibition by 12.71% (95% CI 10.76-14.67, P <0.0001), and led to a 60% reduction in the risk of HTPR (RR=0.40; 95% CI 0.30-0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (IRR=0.68; 95% CI 0.60-0.78), TLR (IRR=0.57; 95% CI 0.44-0.73), TVR (IRR=0.69; 95% CI 0.59-0.81) and stent thrombosis (IRR=0.63; 95% CI 0.40-0.98) with no difference for other outcomes including bleeding, even in trials using drug eluting stents. Drug discontinuation due to adverse effects was however higher with TAPT vs. DAPT (IRR=1.59; 95% CI 1.32-1.91). Conclusions: In patients undergoing PCI, addition of cilostazol to dual antiplatelet therapy results in decreased platelet reactivity and a significant reduction in CV outcomes including stent thrombosis, even in the drug eluting stent era.

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