Value Of Platelet Function Testing Research Articles

Abstract 13031: Real World Outcomes of Prognostic Value of Platelet Function Testing for Five-Year Ischemic Events in Patients Undergoing Percutaneous Coronary Intervention: A Large-Scale Cohort Study

Introduction: Individualized antithrombotic therapy guided by platelet function testing is a hot topic in current study. However, the prognostic value of platelet function testing for long-term ischemic events in percutaneous coronary intervention (PCI) population is still unknown. Objective: To investigate whether platelet function testing (reflected by adenosine diphosphate-induced platelet maximum amplitude [MA ADP ] based on thromboelastogram) is associated with five-year ischemic events in patients undergoing PCI. Methods: 10,724 consecutive patients undergoing PCI in 2013 were enrolled. The traditional cut-off point of MA ADP (47) and the optimal cut-off point of MA ADP (41.8) according to receiver operating curve were selected. The primary endpoint was cardiovascular death. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction, ischemic revascularization, and stroke. Results: A total of 6,290 patients (mean age, 58.27 ± 10.30; male, 77.5%) who had both MA ADP results and completed follow-up were finally included. After five-year follow-up, 143 (2.3%) cardiovascular death and 1,410 (22.4%) MACCE occurred. According to the traditional cut-off point, multivariate COX regression analysis (Figure 1) showed no prognostic value of MA ADP for both cardiovascular death and MACCE (all P >0.05). As for the optimal cut-off point, multivariate COX regression analysis (Figure 2) showed that MA ADP ≥ 41.8 was independently associated with cardiovascular death (HR=1.484, 95% CI: 1.043-2.111, P =0.028) and MACCE (HR=1.138, 95% CI: 1.018-1.272, P =0.023). Conclusions: Our study is the first to report that platelet function testing can help identify individuals at high risk of long-term ischemic events. We proposed a new cut-off point of MA ADP to assess the prognosis of ischemic events, and demonstrated that MA ADP ≥ 41.8 was associated with five-year cardiovascular death and MACCE.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock

While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock. The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock and with available on-treatment ADP-induced platelet aggregation measurements. Out of 233 patients, 74 suffered from a severe BARC3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (p < .001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU). An optimal cutoff value of <12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, the use of VA-ECMO (HR 1.972) or coaxial left ventricular pump (HR 2.593), first lactate (HR 1.093 per mmol/l) and thrombocyte count (HR 0.994 per G/l) were independent predictors of BARC≥3 bleedings. In conclusion, lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in cardiogenic shock warrants further investigation.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: None. Background While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock (CS). Methods The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and with available on-treatment ADP-induced platelet aggregation measurements. Results Out of 233 patients, 74 suffered from a severe BARC 3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (10 AU [IQR 3 - 13] vs. 15 AU [IQR 9 - 25], p &amp;lt; 0.001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU, 95% confidence interval (CI) 0.942-0.994). An optimal cut-off value of &amp;lt;12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, use of VA-ECMO (HR 1.972, 95% CI 1.003-3.879) or coaxial left ventricular pump (HR 2.593, 95% CI 1.509-4.455), first lactate (HR 1.093 per mmol/l, 95% CI 1.037-1.152) and thrombocyte count (HR 0.994 per G/l, 95% CI 0.990-0.998) were independent predictors of BARC≥3 bleedings. There was no significant difference in survival nor ischemic events between patients with low and high on-treatment platelet reactivity. Conclusion: Lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in CS warrants further investigation.

Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial.

The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

Platelet function testing predicts bleeding complications in elderly patients admitted for an acute coronary syndrome: insights from the ANTARCTIC trial

Elderly patients are at high-risk of bleedings, particularly in the setting of acute coronary syndrome treated with an invasive strategy. Treatment adjustment by platelet function testing (PFT) failed to improve clinical outcomes in the randomized ANTARCTIC trial. This prespecified substudy aims at determining the predictive value of PFT on occurrence of bleedings. We analyzed the 877 patients over the age of 75 years included in the ANTARCTIC trial and randomized to a strategy of dose or drug antiplatelet therapy adjustment or a conventional “one size fits all” strategy without PFT. In the monitoring group, patients received prasugrel 5 mg daily after coronary stenting and PFT was done 14 days after randomization and repeated 14 days after treatment adjustment. Occurrence of bleedings was collected up to one year and correlated with PFT. Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n = 181 patients) with one third occurring in the first month. Cutaneous and gastro-intestinal bleedings were the two predominant complications. There was no significant difference in the final treatment between patients with or without clinically relevant bleedings (respectively, clopidogrel 75 mg: 19.9% and 19.6%, prasugrel 5 mg: 77.3% and 77.9%, prasugrel 10 mg: 2.6% and 2.8%; P = 0.91) The main predictive factors of major bleedings in multivariate model were age > 85 years [adj.HR(95% CI): 2.48(1.25;4.91); P = 0.0093] and hemoglobin level (per gram of decrease) [adj.HR(95% CI): 1.45(1.18;1.79); P = 0.0004]. The last PFT was an independent predictive factor of clinically relevant bleedings (adj.HR(95% CI): 0.95(0.90;0.99); P = 0.017). Clinically relevant bleedings were frequent in elderly patients in the setting of acute coronary syndrome. PFT did not improve clinical outcomes but identified the bleeding risk of these patients when the chronic treatment was installed.

Platelet Reactivity and Early Outcomes after Transfemoral Aortic Valve Implantation.

Beyond thromboembolic events, peri-procedural bleeding remains one of the most frequent complications after transcatheter aortic valve implantation (TAVI). The majority of TAVI patients receive a dual anti-platelet treatment (DAPT) regimen. This analysis from the EVERY-TAVI register database aimed to analyse whether the level of on-treatment adenosine diphosphate-induced platelet reactivity predicts early outcomes at 30 days after TAVI. A total of 146 consecutive TAVI patients on DAPT who underwent platelet function testing with the Multiplate analyser were included here. Definition of bleeding events was done according to the Valve Academic Research Consortium-2 (VARC-2) classification. In our cohort, a status of low platelet reactivity (LPR, ≤ 18 units) was observed in 79 patients (54%), while high platelet reactivity (HPR, ≥ 46 units) was present in 18 patients (12%). At 30-day follow-up, the incidence of VARC-2 bleeds was 45.6% (n = 36) in LPR patients and 23.9% (n = 16) in patients without LPR (hazard ratio [HR] 2.10, 95% confidence interval [CI], 1.17-3.79; p = 0.01). In age-adjusted multivariate analysis, a status of LPR was independently associated with VARC-2 bleeding events (HRadj, 2.06, 95% CI, 1.14-3.71; p = 0.02). HPR was not associated with the 30-day risk of death, stroke, or myocardial infarction (p ≥ 0.43). In summary, presence of LPR was associated with bleeding events in patients undergoing TAVI while presence of HPR was not associated with ischaemic outcomes at 30 days. The value of platelet function testing for bleeding risk prediction and for a possible guidance of anti-thrombotic treatment in the elderly TAVI population warrants further investigation.

Abstract 291: Platelet Function Monitoring After Percutaneous Coronary Intervention: Updated Meta-analysis of Randomized Trials.

Background: The need to balance bleeding and clotting risks after percutaneous coronary intervention (PCI) has led to interest in platelet function monitoring as a strategy to improve post-PCI outcomes. The prognostic value of platelet function testing in monitoring response to antiplatelet therapy after PCI remains unclear. Prior studies have been inconclusive. We sought to conduct an updated meta-analysis to address this gap in knowledge. Methods: We conducted a systematic search of EMBASE, PUBMED and the Cochrane libraries for studies since inception to December 2016 on platelet function monitoring. Our search yielded 203 studies, out of which 83 were extracted for full-text review. Only 3 studies met inclusion criteria. We pooled odds ratios using random-effects statistics, Mantel-Haenszel method. I2 and Chi- squared statistic was used to evaluate for heterogeneity. Publication bias was assessed using the funnel plot. Primary outcome was major adverse cardiovascular events (MACE). This was defined in the studies as a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and bleeding complications. Results: The 3 randomized controlled trials that were analyzed involved 3701 patients. There were 550 MACE (29.76%) in the platelet function monitored group compared with 514 (27.74%) in the control. MACE (Figure 1) was not significantly higher for the platelet function monitored group during follow-up compared with control (pooled Odds Ratio:1.11 [95% CI: 0.96-1.28], p = 0.15). Tests for heterogeneity were not significant, with I2 of 0%, Chi2 = 1.52 (p = 0.47); and small study bias was absent on visual inspection of the funnel plot. Conclusions: Platelet function monitoring continues to be used in practice. Results from this meta-analysis show no benefit of platelet function monitoring compared with conventional strategy with regards to MACE after PCI. Future research is needed to further evaluate this finding.

Platelet function testing as a biomarker for efficacy of antiplatelet drugs.

Despite the overwhelming evidence in support of the efficacy of dual antiplatelet therapy with aspirin and clopidogrel, it is also obvious that not all patients benefit from these drugs to the same extent. This interindividual variability in platelet responses may underlie clinical differences in drug efficacy, with potential for optimization of antiplatelet therapy to prevent ischemic events without excessively increasing bleeding risk. This review presents the current evidence regarding platelet function testing for monitoring of antiplatelet therapy, with emphasis on the prognostic value of platelet function testing to predict ischemic and bleeding events. The potential of platelet function testing to provide personalized antiplatelet therapy is also discussed, with an outlook toward the future of platelet function testing in high-risk individuals.

Platelet Function Testing in Patients on Antiplatelet Medications.

Guidelines provide a Class IA recommendation for the use of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI). However, there is interindividual variability in the pharmacodynamic response to antiplatelet medications. Some patients present with a status of high on-treatment platelet reactivity (HPR) during platelet function testing after standard doses of antiplatelet drugs, reflecting a failure to achieve adequate platelet inhibition. As an example, patients with HPR on clopidogrel are at increased risk for thrombotic events, particularly for stent thrombosis and myocardial infarction, but cardiovascular mortality is also elevated. On the contrary, low on-treatment platelet reactivity or an enhanced response to antiplatelet medications has been linked to a higher risk for bleeding. Although both thrombotic and bleeding events are multifactorial in origin, there is supportive evidence for the prognostic value of platelet function testing for risk prediction of both sides of the coin. However, although small studies have provided evidence that treatment adjustments based on platelet function testing results may improve clinical outcomes, the available randomized controlled trials showed no benefit of modifying antiplatelet treatment based on platelet function testing. This review presents the current evidence regarding platelet function testing in patients undergoing PCI. The prognostic value of platelet function testing regarding ischemic and bleeding events is highlighted. Furthermore, the value of platelet function testing for guiding treatment and possible explanations for the so-far negative trial results are presented. The possible future role of platelet function testing for individualized antiplatelet treatment regimens in high-risk patients will be also discussed.

Platelet function testing in clinical diagnostics

Although the utility of platelet function testing is still under debate, the necessity to inhibit platelets in patients suffering from cardiovascular and cerebrovascular disease is undoubted and well proven. The wide variety of available platelet function tests often using different methodologies, the apparent lack of standardization, and finally the emerging evidence on the clinical value of platelet function testing are resulting in a considerable uncertainty in the clinical practice, how to deal with the issue of platelet function testing. Platelet function testing might not only yield clinical benefits for the patients but also economical advantages by identifying the right drug at the right dose for the right patient. This article intends to provide an overview of the current platelet function tests such as light transmittance aggregometry, whole blood impedance aggregometry, the PFA-1001 system, the VerifyNow2 system, flow cytometry, as well as other promising technologies like Plateletworks3, IMPACT-R4, PADA, thromboelastography, and the mean platelet component (MPC), briefly addressing strengths, weaknesses and clinical utility of these tests.