Impact Of Platelet Reactivity Research Articles

Impact of Platelet Reactivity on 1-Year Clinical Outcomes After Endovascular Therapy for Femoropopliteal Lesions

Impact of Platelet Reactivity on 1-Year Clinical Outcomes After Endovascular Therapy for Femoropopliteal Lesions

Impact of platelet reactivity on subclinical valve thrombosis in patients treated with TAVR

Abstract Background and introduction High residual platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention with dual antiplatelet therapy (DAPT) is associated with an increased risk of thrombotic events. The relationship between HPR and the presence of subclinical valve thrombosis (SVT) following transcatheter aortic valve replacement (TAVR) is unknown. Purpose The aim of this study was to determine whether HPR is associated with the occurrence of SVT in patients undergoing TAVR treated with DAPT and to determine independent predictors of SVT. Methods This is a prospective, multicentre study. Patients with symptomatic aortic stenosis successfully treated with TAVR followed by DAPT (aspirin + clopidogrel) for 3 months were included. Patients with monotherapy, oral anticoagulation, or severe renal impairment were excluded. For the purpose of the study, platelet reactivity was measured either with Multiplate analyzer or VerifyNow point-of-care assay at baseline, at 1-2 days post, and 1-3 months post-TAVR. HPR was defined as ≥ 468AU, or ≥208PRU, respectively. The primary endpoint was the incidence of SVT measured by multi-slice CT at 3-months post TAVR in relation to HPR. Secondary objectives included the relationship between HPR following TAVR and the incidence of major adverse cardiac and cerebral clinical events (MACCE), to determine whether a pro-thrombotic inflammatory response is associated with the appearance of SVT and to evaluate factors associated with the occurrence of SVT. Results A total of 169 patients were included, the mean age was 81.5±5 and 51% were female. The overall rate of SVT was 22%. Patients with HPR demonstrated a similar incidence of SVT to those without (23,7% vs 33,6%: p=0,29). The overall bleeding rate was 4,9%. No differences in the rate of stroke at 1-year follow-up were observed (no SVT group 1.5% vs SVT group 2.6%: p=0.6). Independent predictors of SVT, were: dyslipemia OR 0,38 (0,15-0,96) p=0,039, creatinine clearance 0.98 (0.96.1.0, p=0.04), self-expandable valve OR 3,57 (1,40-9,06); p=0,006 and prosthesis size 0,78 (0,64-0,96): p=0,009. Patients with SVT expressed increased inflammatory parameters at 6 months compared to those without SVT CD14+ CD16-: 76,6±9,9 vs 70,7±13,9: p=0.02. Conclusion In contrast to coronary interventions, for the first time we have demonstrated that HPR does not appear to be associated with the development of SVT in TAVR patients treated with DAPT.

Impact of platelet reactivity on late lumen loss after primary percutaneous coronary intervention with second-generation drug-eluting stents in acute coronary syndrome

Impact of platelet reactivity on late lumen loss after primary percutaneous coronary intervention with second-generation drug-eluting stents in acute coronary syndrome

Impact of Platelet Reactivity in ACS Patients on Clinical Outcomes with Triple Antithrombotic Therapy.

Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients on oral anticoagulants (OAC) remains a clinical conundrum. In fact, combining an OAC with dual antiplatelet therapy (triple antithrombotic therapy, TAT) increases the risk of bleeding. Clopidogrel is the only thienopyridine recommended in TAT patients. Whether its response plays a relevant role in this setting remains uncertain. We aimed to evaluate the level of platelet reactivity inhibition (PRI) achieved by oral TAT in Acute Coronary Syndrome (ACS) patients undergoing PCI and its relationship with outcomes. We performed a multicenter prospective observational study and assessed PRI by vasodilator-stimulated phosphoprotein (VASP) index following a loading dose of clopidogrel. The primary endpoint was the incidence of major adverse cerebral or cardiovascular events (MACCE) at six months based on High on Treatment Platelet Reactivity (HTPR, VASP > 50%). The secondary endpoint was the incidence of bleeding at six months based on Low on Treatment Platelet Reactivity (LTPR, VASP < 16%). 491 patients were followed up for six months: 7.7% experienced MACCE and 17.3% experienced bleeding. There was no significant relationship between HTPR and MACCE, neither between LTPR and bleeding. Vitamin-K antagonist (VKA) treatment was associated with more MACCE and bleeding events, and the majority of events occurred within the first months. VASP index failed to predict outcomes in post-ACS patients with TAT. We confirm that direct acting OAC should be prioritized over VKA in TAT regimen.

Impact of platelet reactivity on long-term prognosis in Korean patients receiving percutaneous coronary intervention

Both high and low platelet responses to clopidogrel are highly associated with mortality. A therapeutic window for platelet reactivity was recently determined to be an important factor for improving clinical outcomes after percutaneous coronary intervention (PCI). We evaluated the impact of the antiplatelet activity of clopidogrel on long-term clinical outcomes in Korean patients receiving PCI. We analyzed the clinical outcomes of 814 Korean patients undergoing PCI for a median of 48 months. Platelet reactivity on clopidogrel was measured with the VerifyNow P2Y12 assay. The primary endpoint was all-cause death at 4 years. Patients were classified into three groups according to the P2Y12 reaction unit (PRU): low platelet reactivity (LPR; PRU < 85), normal platelet reactivity (NPR; 85 ≤ PRU < 208), and high platelet reactivity (HPR; PRU ≥ 208). The incidence of all-cause death was 7.0% in the LPR group, 1.5% in the NPR group, and 6.2% in the HPR group (log-rank p = 0.002). Based on multivariate analyses, all-cause death was significantly higher in both the LPR and HPR groups than in the NPR group (LPR, hazard ratio [HR]: 5.095; 95% confidence interval [95% CI]: 1.360–19.080, p = 0.016; HPR, HR: 3.315; 95% CI: 1.145–9.593, p = 0.027). Both LPR and HPR were significantly associated with long-term mortality in Korean patients receiving PCI, which suggests that the therapeutic concept of PRU may be an important prognostic factor.

Impact of platelet reactivity on 5-year clinical outcomes following percutaneous coronary intervention: a landmark analysis.

We investigated the impact of suboptimal platelet reactivity on clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients with stable coronary artery disease undergoing elective PCI. Platelet reactivity was measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the incidence of ischemic or bleeding events at 1month and 5years. Patients with high platelet reactivity (HPR) showed significantly higher rates of ischemic events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and beyond 1month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95). Conversely, compared with patients without low platelet reactivity (LPR), patients with LPR presented significantly higher rates of bleeding only during the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is associated with ischemic events even beyond the 1st month after PCI. The association of LPR with bleeding events seems to be confined to the periprocedural period.

TCTAP A-023 Clinical Impact of Platelet Reactivity and Gene Polymorphisms Tests in Patients with Interventional Procedures for Coronary Artery Disease

TCTAP A-023 Clinical Impact of Platelet Reactivity and Gene Polymorphisms Tests in Patients with Interventional Procedures for Coronary Artery Disease

TCT-496 Impact of platelet reactivity on clopidogrel after PCI with 2nd generation DES on late lumen loss

TCT-496 Impact of platelet reactivity on clopidogrel after PCI with 2nd generation DES on late lumen loss

Impact of Obesity and the Metabolic Syndrome on Response to Clopidogrel or Prasugrel and Bleeding Risk in Patients Treated After Coronary Stenting

This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.

First experience of a bioresorbable vascular scaffold implantation in left main stenosis

[1] Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505–16. [2] Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171–5. [3] Cuisset T, Frere C, Quilici J, et al. High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome. J Thromb Haemost 2006;4:542–9. [4] Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007;49:2312–7. [5] Cuisset T, Cayla G, Frere C, et al. Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment? EuroIntervention 2009;5:325–9. [6] Sibbing D, Schulz S, Braun S, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010;8:250–6. [7] Campo G, Parrinello G, Ferraresi P, et al. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011;57:2474–83. [8] Cuisset T, Quilici J, LoosveldM, et al. Comparison between initial and chronic response to clopidogrel therapy after coronary stenting for acute coronary syndrome and influence on clinical outcomes. Am Heart J 2012;164(3):327–33. [9] Alexopoulos D, Dimitropoulos G, Davlouros P, et al. Prasugrel overcomes high onclopidogrel platelet reactivity post-stentingmore effectively than high-dose (150-mg) clopidogrel: the importance of CYP2C19*2 genotyping. JACC Cardiovasc Interv 2011;4:403–10.

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Aspirin is an antiplatelet drug widely used for the prevention of cardiovascular disease; however, it is known to increase bleeding events. A low response to aspirin was reported to correlate with poor prognosis in patients undergoing antiplatelet therapy with aspirin. The aim of this study was to evaluate the impact of the antiplatelet activity of aspirin on cardiovascular and bleeding events in Japanese patients. We analyzed the clinical course of 239 Japanese patients undergoing antiplatelet therapy with aspirin for a median of 64 months in this study. Their residual platelet reactivity was examined at enrollment and after 2 years. The co-primary endpoints were the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) and bleeding events. The annual incidence of MACCEs and major bleeding events was 3.7% and 0.48%, respectively. With defined criteria, 67 patients (28%) were classified as low responders based on the platelet aggregability measured at enrollment. Low response to aspirin was not associated with increased MACCEs, while it clearly increased MACCEs in patients less than 70 years old (low responders 36.9% vs. responders 14.8%, log rank p=0.008). Five major types of bleeding occurred in the responders, but not in low responders, although the difference was not statistically significant (p= 0.07). Low response to aspirin was not associated with the increase of long-term MACCEs, while it increased MACCEs in patients less than 70 years old; however, it tended to decrease major bleeding events in Japanese patients.

Impact of Platelet Reactivity on Clinical Outcomes After Percutaneous Coronary Intervention: A Collaborative Meta-Analysis of Individual Participant Data

The purpose of the study was to systematically evaluate the significance of platelet reactivity on clopidogrel treatment on adverse cardiovascular events using a collaborative meta-analysis using patient-level data for the VerifyNow P2Y12 assay (Accumetrics, San Diego, California). Clinical evidence has been controversial regarding the influence of clopidogrel on treatment platelet reactivity and ischemic outcomes. MEDLINE, Scopus, and the Cochrane library databases were searched through January 2010. A database containing individual patient-level time-to-event data was generated from identified studies. The primary outcome of interest was a composite of death, myocardial infarction (MI), or stent thrombosis. Secondary outcomes included the incidence of: 1) death; 2) MI; and 3) stent thrombosis. A total of 6 studies with 3,059 patients was included. In each study, clopidogrel responsiveness was assessed using the same point-of-care assay after percutaneous coronary intervention. The primary endpoint occurred more frequently in higher quartiles of P2Y(12) reaction unit (PRU) values: quartile I, 5.8%; quartile II, 6.9%; quartile III, 10.9%; quartile IV, 15.8% (p < 0.001). Taking quartile I as referent, the hazard ratios (HRs) for the primary endpoint were as follows: quartile II, HR: 1.13 (95% confidence interval [CI]: 0.72 to 1.78; p = 0.60); quartile III, HR: 1.82 (95% CI: 1.20 to 2.75; p = 0.005); quartile IV, HR: 2.62 (95% CI: 1.78 to 3.87; p < 0.001). On a continuous scale, every 10-U increase in PRU was associated with a significantly higher rate of the primary endpoint (HR: 1.04; 95% CI: 1.03 to 1.06; p < 0.0001). According to receiver-operating characteristic curve analysis, a PRU value of 230 appeared to best predict death, MI, or stent thrombosis (p < 0.001). A PRU value ≥230 was associated with a higher rate of the composite primary endpoint (HR: 2.10; 95% CI: 1.62 to 2.73; p < 0.0001), as well as the individual endpoints of death (HR: 1.66; 95% CI: 1.04 to 2.68; p = 0.04), MI (HR: 2.04; 95% CI: 1.51 to 2.76; p < 0.001), and stent thrombosis (HR: 3.11; 95% CI: 1.50 to 6.46; p = 0.002). In this collaborative meta-analysis, the level of on-treatment platelet reactivity according to the P2Y(12) assay is associated with long-term cardiovascular events after percutaneous coronary intervention, including death, MI, and stent thrombosis.

Usefulness of Mean Platelet Volume as a Biomarker for Long-Term Outcomes After Percutaneous Coronary Intervention

Larger size platelets have enhanced reactivity. The mean platelet volume (MPV) is a marker of platelet activation and is usually measured as part of blood testing. The aim of the present study was to investigate the utility of the MPV as a biomarker in prognosticating the long-term outcomes after percutaneous coronary intervention (PCI). The baseline MPV values from consecutive patients undergoing PCI were screened. Of the 1,432 patients, the composite primary end point of mortality or myocardial infarction at 1 year occurred in 80 (5.6%). The patients in the highest tertile (MPV >9.1 fL) had an increased frequency of the primary end point compared to those in the mid (8.1 to 9.1 fL) and lowest (<8.1 fL) tertiles (9.0%, 4.5%, and 3.5%, respectively; p <0.01). Logistic regression analysis demonstrated diabetes (odds ratio 2.44, 95% confidence interval 1.48 to 4.00) and highest tertile of MPV (odds ratio 2.42, 95% confidence interval 1.47 to 3.99) as the best predictors of adverse outcomes. In patients with acute coronary syndrome, the preprocedural MPV and troponin levels demonstrated a comparable predictive relation to the primary end point (receiver operator characteristics curve analysis, area under the curve 0.64, p = 0.01; and 0.63, p = 0.01, respectively). In conclusion, an elevated MPV was a strong independent predictor of long-term outcomes after PCI. The preprocedural MPV had prognostic value similar to that of troponin in patients with acute coronary syndrome. These findings could be of importance in the clinical evaluation of patients before PCI and the design of future studies assessing antiplatelet therapies.

Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement.

In patients undergoing percutaneous coronary intervention (PCI), a link between bleeding and excess mortality has been demonstrated. A potential association of platelet response to clopidogrel and bleeding has not been well established yet. The aim of the present study was to assess the impact of clopidogrel responsiveness on the risk of bleeding in clopidogrel-treated patients undergoing PCI. Patients (n=2533) undergoing PCI after pretreatment with 600 mg of clopidogrel were enrolled in this study. Blood was obtained directly before PCI. Adenosine-diphosphate (ADP)-induced platelet aggregation was assessed on a Multiplate analyzer. The primary endpoint was the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major bleeding and the secondary endpoint was in-hospital TIMI minor bleeding. Receiver-operator curve (ROC) analysis was used to derive the optimal platelet aggregation value defining enhanced clopidogrel responders for the association of measurements with major bleeding. Thirty-four (1.3%) major bleeding events and 137 (5.4%) minor bleeding events were observed. The risk of a major bleeding was significantly higher in patients (n=975) with an enhanced response to clopidogrel as compared with the remaining patients (n=1558) (2.2 vs. 0.8%, unadjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3-5.2, P=0.005; adjusted OR 3.5, 95% CI 1.6-7.3, P=0.001). No significant differences between both groups were observed for the occurrence of minor bleeding events (P=0.68). Enhanced clopidogrel responsiveness is associated with a higher risk of major bleeding. Whether guidance of antiplatelet treatment based on platelet function testing proves useful for avoiding bleeding events warrants further investigation.

Impact of Platelet Reactivity on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

This study sought to determine the prognostic implications of high platelet reactivity (HPR) assessed in type 2 diabetes mellitus (T2DM) patients while in their steady-state phase of dual antiplatelet therapy. Type 2 diabetes mellitus patients have increased platelet reactivity compared with nondiabetic patients. Whether HPR assessed in T2DM while in their steady-state phase of dual antiplatelet therapy is associated with an increased risk of major adverse cardiovascular events (MACE) is unknown. Platelet function analyses, which included measures of platelet aggregation and activation, were performed in 173 T2DM patients with coronary artery disease on chronic treatment with aspirin and clopidogrel. The HPR was defined as the upper quartile of maximal platelet aggregation (Agg(max)) after 20 micromol/l adenosine diphosphate stimuli. Patients were followed up for 2 years and MACE were recorded. A total of 41 MACE occurred in 34 patients (19.7%) during the 2-year follow-up. The MACE occurred in 15.2%, 12.2%, 12.2%, and 37.7% of patients from the lowest to upper quartile, respectively (p = 0.005). The HPR was the strongest independent predictor of MACE (hazard ratio 3.35, 95% confidence interval [CI] 1.68 to 6.66, p = 0.001). Receiver-operating characteristic analysis indicated that a cutoff value of 62% Agg(max) best predicted MACE (37.8% vs. 13.2%, odds ratio 3.96, 95% CI 1.8 to 8.7, p < 0.001). Patients with HPR had up-regulation of multiple platelet signaling pathways (p < 0.0001 for all assays), indicative of a global hyperreactive platelet status. High platelet reactivity determined in T2DM patients with coronary artery disease while on chronic dual antiplatelet therapy is associated with a higher risk of long-term adverse cardiovascular events, suggesting the need for tailored antithrombotic drug regimens in these high-risk patients.

Impact of Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent Thrombosis

We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis. No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis. We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mumol adenosine 5'-diphosphate > or =70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up. The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041). Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.