Role Of Platelet Function Testing Research Articles

Abstract Number: LBA4 Platelet Function Testing and Acute Thrombotic Events in Intracranial Aneurysm Patients Undergoing Flow Diversion

Introduction Introduction The role of platelet function testing in patients with intracranial aneurysms undergoing flow diversion remains controversial with limited evidence of its influence on thrombotic outcomes. We report an observational cohort analysis evaluating the association of P2Y12 assay testing with thrombotic events in patients undergoing flow diversion. Methods We performed a retrospective review of our prospectively maintained procedural database to identify patients who underwent flow diversion between January 2020 and July 2022. One physician within our practice never performs P2Y12 assay testing. All other physicians utilize P2Y12 assay testing as part of routine practice. These two different patient cohorts were compared. Acute thrombotic events were our primary outcome. Secondary outcomes included delayed intracerebral hemorrhage, intimal hyperplasia without clinical sequalae, and transient neurologic deficits. Results We identified 150 patients who underwent flow diversion at our institution between January 2020 and July 2022. Median age was 59 years old (Interquartile range (IQR) 49–67), with 113 females (82.5%) and 24 males (17.5%). Out of 150 patients, 93 (62.0%) patients were treated by physicians who performed routine pre and postoperative testing of aspirin and Plavix assays, with subsequent adjustment of antithrombotic dosing accordingly, while 57 patients (38.0%) were treated by the single physician who prescribes aspirin and clopidogrel pre‐operatively without testing. In all, seven out of 150 patients (4.7%) had an acute thrombotic event requiring intraarterial anti‐thrombotic infusion or urgent thrombectomy, or both. Of these, six where from the 93 patient testing cohort (6.5%), and one in 57 patients non‐testing cohort (1.8%) (p = 0.2). Patients who had a thrombotic event were more likely to have underlying atrial fibrillation (28.6% vs 4.9%, p = 0.01) but otherwise had similar demographics, vascular risk factors, maximal aneurysmal diameter, and parent vessel diameter (Table 1). In a multivariable analysis adjusting for age, maximal aneurysm diameter, ruptured aneurysms, and atrial fibrillation, P2Y12 sensitivity assay testing was not significantly associated with acute thrombotic events in aneurysm patients undergoing flow diversion (Odds Ratio (OR) = 0.15, 95% Confidence Interval (CI) = 0.01‐2.67), p = 0.2). Secondary outcomes were also comparable between both groups; transient neurologic deficits were noted in 4/93 in the testing group (4.3%), and 6/57 in the non‐testing group (10%) (p = 0.14), intracranial hemorrhage occurred in only 2 patients, both in the testing group (p = 0.3), and mild intimal hyperplasia was observed in 18.3% in the testing group versus 12.3% in the non‐testing group (p = 0.33). Conclusions Platelet function testing showed no significant correlation with thrombotic events or outcomes in our cohort. The role of platelet function testing remains controversial, albeit widely used in patients undergoing flow diversion of intracranial aneurysms.

Role of platelet function testing in acute coronary syndromes: a meta-analysis

ObjectiveThis meta-analysis aimed to evaluate whether using platelet function testing (PFT) in acute coronary syndromes (ACS) to personalise antiplatelet therapy including a P2Y12 antagonist offers any clinical benefits to indicate...

The Current Role of Platelet Function Testing in Clinical Practice.

Platelet dysfunction, whether hereditary or acquired, may increase an individual's risk of spontaneous, posttraumatic, or postoperative bleeding. Conversely, increased platelet reactivity on antiplatelet agents following vascular (in particular, coronary vascular) intervention may increase the risk of thrombosis and adverse vascular events. The aim of platelet function testing is to identify and characterize platelet dysfunction in these settings to inform bleeding/ thrombosis risk and guide perioperative prophylactic management strategies. A vast array of screening and diagnostic tests is available for this purpose. The successful clinical application of platelet function tests depends on the knowledge of their analytical strengths and limitations and the correct extrapolation of derived results to a particular clinical scenario. This review critically appraises traditional and contemporary platelet function testing focusing on their role in clinical practice.

Considerations for Antiplatelet Management of Carotid Stenting in the Setting of Mechanical Thrombectomy: A Delphi Consensus Statement.

There are only few data and lack of consensus regarding antiplatelet management for carotid stent placement in the setting of endovascular stroke treatment. We aimed to develop a consensus-based algorithm for antiplatelet management in acute ischemic stroke patients undergoing endovascular treatment and simultaneous emergent carotid stent placement. We performed a literature search and a modified Delphi approach used Web-based questionnaires that were sent in several iterations to an international multidisciplinary panel of 19 neurointerventionalists from 7 countries. The first round included open-ended questions and formed the basis for subsequent rounds, in which closed-ended questions were used. Participants continuously received feedback on the results from previous rounds. Consensus was defined as agreement of ≥70% for binary questions and agreement of ≥50% for questions with >2 answer options. The results of the Delphi process were then summarized in a draft manuscript that was circulated among the panel members for feedback. A total of 5 Delphi rounds were performed. Panel members preferred a single intravenous aspirin bolus or, in jurisdictions in which intravenous aspirin is not available, a glycoprotein IIb/IIIa receptor inhibitor as intraprocedural antiplatelet regimen and a combination therapy of oral aspirin and a P2Y12 inhibitor in the postprocedural period. There was no consensus on the role of platelet function testing in the postprocedural period. More and better data on antiplatelet management for carotid stent placement in the setting of endovascular treatment are urgently needed. Panel members preferred intravenous aspirin or, alternatively, a glycoprotein IIb/IIIa receptor inhibitor as an intraprocedural antiplatelet agent, followed by a dual oral regimen of aspirin and a P2Y12 inhibitor in the postprocedural period.

Utility of P2Y12 Reactive Unit Assessment on Ticagrelor in Cerebral Aneurysms Treated with Intracranial Stenting and Flow Diversion: Cohort Study and Case Report From Two Neurovascular Centers

Dual antiplatelet therapy consisting of aspirin and clopidogrel is the standard of care for neurointerventional stenting and flow diversion. Platelet function testing has been increasingly performed to identify patients with a hypo- or hyper-response to clopidogrel. Ticagrelor has been a popular alternative antiplatelet agent for such patients. We assessed the role of platelet function testing in patients receiving ticagrelor and undergoing stenting or flow diversion. The data from patients who had undergone stent-assisted coiling or Pipeline flow diversion of a cerebral aneurysm with ticagrelor therapy at any point during their treatment course from May 2017 to August 2019 at a single academic institution in the United States were retrospectively reviewed. Platelet function testing was used to determine the P2Y12 reactive units (PRUs), and the results were correlated with the procedural complications. A total of 28 patients with 29 aneurysms were treated while receiving ticagrelor. Of the 29 aneurysms, 16 (55.2%) were treated with flow diversion and 13 (44.8%) with stent-assisted coiling. Four thromboembolic complications (13.8%) and no hemorrhagic complications developed. Of the 8 patients with ≥1 PRU value >100, 4 (50%) had experienced a thromboembolic complication. The patients without a PRU value >100 did not experience any complications. A risk of thromboembolic complications exists for patients receiving ticagrelor, which correlated with the PRUs in the present preliminary study. The findings from the present study suggest that the safe PRU range for patients receiving ticagrelor should be shifted to 0-100, which is lower than that of clopidogrel, thought to be 60-210. Further validation of the optimal PRU range for patients receiving ticagrelor is necessary.

Antiplatelet strategies in elderly people: still a long way to go

Outcomes of patients with acute coronary syndrome undergoing percutaneous coronary intervention have been significantly improved with the potent P2Y12 receptor inhibitors prasugrel and ticagrelor. 1 Wiviott SD Braunwald E McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357: 2001-2015 Crossref PubMed Scopus (5562) Google Scholar , 2 Wallentin L Becker RC Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361: 1045-1057 Crossref PubMed Scopus (5545) Google Scholar Elderly patients comprise a growing subset of the acute coronary syndrome population. This subset is characterised by multiple organ changes and various comorbidities, which altogether culminate in an increased risk of both ischaemic and bleeding complications after percutaneous coronary intervention. Platelet function testing has been established and validated to predict ischaemic and bleeding events in patients treated with percutaneous coronary intervention. 3 Aradi D Kirtane A Bonello L et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J. 2015; 36: 1762-1771 Crossref PubMed Scopus (268) Google Scholar , 4 Tantry US Bonello L Aradi D et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013; 62: 2261-2273 Summary Full Text Full Text PDF PubMed Scopus (756) Google Scholar However, previous studies, 5 Collet JP Cuisset T Range G et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012; 367: 2100-2109 Crossref PubMed Scopus (759) Google Scholar , 6 Aradi D Storey RF Komocsi A et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2014; 35: 209-215 Crossref PubMed Scopus (213) Google Scholar enrolling mostly low-risk patients with little use of potent antiplatelet drugs, have been unable to show clinical superiority of strategies that implemented platelet function testing for treatment guidance. Nevertheless, elderly patients undergoing percutaneous coronary intervention represent a high-risk cohort that might derive clinical benefit from platelet function testing to monitor and adjust the level of platelet inhibition. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trialPlatelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Full-Text PDF

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.

From Arctic to Antarctic: Is There any Remaining Role for Platelet Function Testing to Tailor Therapy after Coronary Stent Implantation?

From Arctic to Antarctic: Is There any Remaining Role for Platelet Function Testing to Tailor Therapy after Coronary Stent Implantation?

Clopidogrel Response Variability

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is standard therapy following acute coronary syndrome and percutaneous coronary intervention. Despite the use of potent antiplatelet agents, vascular events continue to occur. Lack of response to clopidogrel therapy has been widely investigated using various methods of platelet function testing. These studies have consistently found an association between poor clopidogrel response and an increased risk of vascular events. Strategies to overcome this problem include higher clopidogrel doses or the use of an alternative P2Y12 agent. To date, the majority of studies investigating tailored antiplatelet therapy have failed to show any reduction in clinical events likely due to the low-risk population studied. Despite this lack of benefit from altering therapy, platelet function testing may be done in certain patient populations. Patients at high risk of deleterious outcomes from stent thrombosis may be an appropriate patient population for platelet function testing to ensure adequate response to therapy. In addition, emerging data suggests a potential role for platelet function testing to assess for bleeding risk. The purpose of this article is to review the key studies demonstrating response variability to clopidogrel therapy, strategies to overcome variability, and practical considerations for the clinician.

Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding?

The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.

Personalized Antiplatelet Therapy

It is well established that high on-treatment platelet reactivity to adenosine diphosphate during clopidogrel therapy is an independent risk factor for ischemic event occurrences in a postpercutaneous coronary intervention patients. However, the precise role of platelet function testing remains debated. Platelet function testing to ensure optimal platelet inhibition has been recommended by some authorities to improve outcomes in patients treated with clopidogrel. Recent prospective, randomized trials of personalized antiplatelet therapy have failed to demonstrate a benefit of platelet function testing in improving outcomes. In this review article, we discuss the mechanisms responsible for clopidogrel nonreponsiveness, recent trials of platelet function testing, and other new developments in the field of personalized antiplatelet therapy.

Tratamiento antiagregante plaquetario personalizado

It is well established that high on-treatment platelet reactivity to adenosine diphosphate during clopidogrel therapy is an independent risk factor for ischemic event occurrences in a postpercutaneous coronary intervention patients. However, the precise role of platelet function testing remains debated. Platelet function testing to ensure optimal platelet inhibition has been recommended by some authorities to improve outcomes in patients treated with clopidogrel. Recent prospective, randomized trials of personalized antiplatelet therapy have failed to demonstrate a benefit of platelet function testing in improving outcomes. In this review article, we discuss the mechanisms responsible for clopidogrel nonreponsiveness, recent trials of platelet function testing, and other new developments in the field of personalized antiplatelet therapy.Full English text available from:www.revespcardiol.org/en

Platelet Function Testing in Contemporary Clinical and Interventional Practice

Dual antiplatelet therapy with a combination of aspirin and an inhibitor of the ADP P2Y12 receptor is the recommended treatment for patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention (PCI). However, patients may continue to have ischemic recurrences, including stent thrombosis, which have been linked with the well-known variability in individual response to antiplatelet therapy, and clopidogrel in particular. There are currently several assays available to measure platelet reactivity, and platelet function testing has been shown to be a valuable tool to assess the pharmacodynamic efficacy of antiplatelet drugs. Moreover, platelet reactivity has important prognostic implications, as several studies have shown an association with thrombotic and bleeding events in patients with high and low platelet reactivity, respectively. Consequently, over the past years there has been a plethora of studies investigating the optimal range of platelet reactivity associated with the highest protection against ischemic complications and the lowest risk of bleeding. Given the correlation between on-treatment platelet reactivity and outcomes, the use of platelet function testing has also been advocated to create personalized antiplatelet therapy. Several studies have been conducted in this field, but major clinical trials have failed to demonstrate a benefit of such a strategy in improving clinical outcomes. Indeed, inherent limitations of these trials may have contributed to their failure. The present manuscript provides an overview on the role of platelet function testing in contemporary clinical and interventional practice.

Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention

Optimizing outcomes after percutaneous coronary intervention (PCI) requires balancing between the risks of thrombotic and bleeding events in individual patients.1–3 However, finding the optimal balance is not always straightforward since the risks of thrombotic and bleeding complications may differ extremely between individuals. In addition, the individual effects of anticoagulant and antiplatelet drugs are not uniform in patients.4 Recent European guidelines1,3 recommend the use of prasugrel or ticagrelor instead of clopidogrel in all PCI-treated acute coronary syndrome (ACS) patients without contraindication, acknowledging that laboratory assessment of P2Y12-receptor inhibition may be considered only in selected cases when clopidogrel is used.1 However, there is no guidance with respect to the appropriate methodology and the suggested interpretation of results. The Working Group on Thrombosis of the European Society of Cardiology aimed to review the available evidence and the clinical relevance of platelet function testing in order to reach a consensus regarding the methodology, evaluation, and clinical interpretation of platelet function in patients undergoing PCI. Regarding the choice between available P2Y12-inhibitors, the 2011 ESC guidelines on non-ST segment elevation acute coronary syndromes (NSTE-ACS)1 and the 2012 guidelines on ST-segment elevation myocardial infarction3 recommend prasugrel and ticagrelor for all ACS patients without contraindication, and clopidogrel is only recommended if these agents are not available. Despite the restrictive recommendations for clopidogrel, it still holds a class I indication in ACS due to the large differences in the availability of the new-generation P2Y12-inhibitors among European countries. According to the 2011 ACCF/AHA/SCAI guidelines for PCI,5 a P2Y12-inhibitor should be given for ACS patients without preferring novel P2Y12-inhibitors over clopidogrel. Similarly, the 2012 ACCF/AHA unstable angina/non-ST-segment elevation myocardial infarction guidelines6 and the 2013 ACCF/AHA ST-elevation myocardial infarction guidelines …

HeartWare left ventricular assist device thrombosis in aspirin non-responder

Patient characteristics that increase the risk of continuous-flow left ventricular assist device thrombosis have not been well established. We report a case of HeartWare thrombosis in a patient with aspirin hyporesponsiveness, and discuss the role of platelet function testing in preventing this severe complication. There is a need for clinical trials determining optimal antiplatelet therapy in patients supported with left ventricular assist devices, and consensus regarding modification of antiplatelet therapy after device thrombosis.

The role of clopidogrel in the management of ischemic heart disease

Placebo-controlled randomized trials have demonstrated the efficacy of clopidogrel in combination with aspirin across a broad range of clinical presentations. Recent trials have addressed several remaining issues regarding clopidogrel therapy. Three randomized trials examined the role of platelet function testing (PFT) in clopidogrel-treated patients. The results do not support the use of PFT to adjust clopidogrel dose after percutaneous coronary intervention (PCI), particularly in patients with stable angina or ischemia, in whom event rates are low irrespective of on-treatment reactivity. Doses greater than clopidogrel 150 mg daily are required to sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele carriers. Clopidogrel response variability also influences the time to platelet recovery after drug discontinuation, and a proof-of-principle study supports the concept of using PFT for surgical timing. Unlike its efficacy in the setting of acute coronary syndrome (ACS) and PCI, prasugrel was not superior to clopidogrel in medically treated patients recovering from ACS. Current data do not support routine PFT to guide antiplatelet therapy in patients undergoing nonurgent PCI. The role of PFT to optimize therapy in ACS patients remains unaddressed, and further study is needed to confirm its promise in guiding surgical timing in patients who have discontinued therapy. Clopidogrel remains an important therapeutic option for patients presenting after an ACS who did not undergo initial revascularization.

Modern antiplatelet management of coronary artery bypass patients: a role of platelet function testing in decision making

We read with great interest the recently published study by Williams et al. [1]. The authors sought to determine the relationship between postoperative clopidogrel and clinical and angiographic outcomes following coronary artery bypass grafting (CABG) [1]. Although clopidogrel is now recommended as postoperative antiplatelet therapy in patients with recent acute coronary syndromes, some other circumstances such as off-pump CABG, performed endarterectomy, and extensive severe coronary artery disease with small target vessels, warrant the use of both clopidogrel and aspirin following surgical revascularization [2]. In present study by Williams et al. [1], postoperative antiplatelet therapy was left to physician discretion, thus creating patient selection bias since above mentioned circumstances requiring dual antiplatelet therapy (dAPT) could influence angiographic as well as clinical outcomes. Aortocoronary vein graft disease is composed of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia, and atherosclerosis [3]. Early thrombosis is a major cause of vein graft attrition during the first month after CABG [3]. Since the present study assessed clinical outcome [1] it would be interesting if authors included in analysis patients who died prior to 30 days postoperatively. It would be interesting to elucidate how many patients of those who died prior to 30 days postoperatively were on dAPT versus mono antiplatelet therapy early after CABG? In our opinion, the lack of data concerning objective quantification of the antiplatelet effect of aspirin and clopidogrel constitutes a major drawback of the study. Expected inhibition of platelet function is not always achieved after aspirin and/or clopidogrel administration. The frequency of low responsiveness for the 2 drugs has been reported to range from 1 to 45 % [4, 5] and such a phenomenon could certainly explain in some degree ischemic events after CABG. When assessing relationship between postoperative dAPT and both clinical and angiographic outcomes following CABG, the role of aspirin should inextricably be included into considerations. Within dAPT the possible impact of each antiplatelet agent (aspirin and clopidogrel) on clinical and angiographic outcomes should separately be assessed by drug specific platelet function tests, facilitating individual therapeutic approach for each antiplatelet agent postoperatively. Such an approach could distinguish patients with high residual platelet activity, thus proclivity to ischemic events, from those with enhanced platelet inhibition, thus proclivity to bleeding events (notably, not captured in present trial). In our recent study [5], we analyzed the proportion of patients with aspirin resistance, both preand postoperatively. Considering all CABG patients, we observed 31/99 (31.3 %) patients with aspirin resistance preoperatively [5]. Postoperatively, we registered 46/99 (46.5 %) CABG patients with aspirin resistance, suggesting platelet hyperactivity [5]. A postoperatively registered increase of 15.2 % in the proportion of patients with aspirin resistance was found to be significant (p = 0.04) as well as higher prevalence of aspirin resistance within diabetic subpopulation (58.5 vs 38 %, p = 0.04). Postoperatively, we observed significant increase in values of platelet function M. Petricevic (&) B. Biocina I. Safradin Department of Cardiac Surgery, University Hospital Center Zagreb, University of Zagreb School of Medicine, Kispaticeva 12, 10000 Zagreb, Croatia e-mail: petricevic.mate@gmail.com

Platelet Function Measurement–Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery

Aspirin and clopidogrel therapy is associated with a variable bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the role of platelet function testing in clopidogrel-treated patients undergoing CABG. One hundred eighty patients on background aspirin with/without clopidogrel therapy undergoing elective first time isolated on-pump CABG were enrolled in a prospective single-center, nonrandomized, unblinded investigation (Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG] study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP-induced platelet-fibrin clot strength [MA(ADP)]) was determined by thrombelastography; CABG was done within 1 day, 3-5 days, and >5 days in patients with an MA(ADP) >50 mm, 35-50 mm, and <35 mm, respectively. The primary end point was 24-hour chest tube drainage and key secondary end point was total number of transfused red blood cells. Equivalence was defined as ≤25% difference between groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81-107%) of the amount observed in clopidogrel-naive patients, and the total amount of red blood cells transfused did not differ between groups (1.80 U versus 2.08 U, respectively, P=0.540). The total waiting period in clopidogrel-treated patients was 233 days (mean, 2.7 days per patient). A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and ≈50% shorter waiting time than recommended in the current guidelines. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00857155.

Evolving role of platelet function testing in coronary artery interventions

The substantial reduction in ischemic events provided by the dual antiplatelet regimen with aspirin and clopidogrel is well documented in patients with acute coronary syndrome and patients undergoing percutaneous coronary intervention. Recently the variable response to the antiplatelet agents has received considerable attention after several “boxed warnings” on clopidogrel. This led to intense controversy on pharmacokinetic, pharmacodynamic, and pharmacogenomic issues of antiplatelet drugs, especially clopidogrel. Research use of platelet function testing has been successfully validated in identifying new antiplatelet drugs like prasugrel and ticagrelor. These platelet function assays are no longer regarded just as a laboratory phenomenon but rather as tools that have been shown to predict mortality in several clinical trials. It is believed that suboptimal response to an antiplatelet regimen (pharmacodynamic effect) may be associated with cardiovascular, cerebrovascular, and peripheral arterial events. There has been intense controversy about this variable response of antiplatelet drugs and the role of platelet function testing to guide antiplatelet therapy. While the importance of routine platelet function testing may be uncertain, it may be useful in high-risk patients such as those with diabetes mellitus, diffuse three vessels coronary artery disease, left main stenosis, diffuse atherosclerotic disease, and those with chronic renal failure undergoing percutaneous coronary intervention. It could also be useful in patients with suspected pharmacodynamic interaction with other drugs to assure the adequacy of platelet inhibition. While we wait for definitive trials, a predictive prognostic algorithm is necessary to individualize antiplatelet therapy with P2Y12 inhibitors based on platelet function assays and genetic testing.

Translational platelet research in patients with coronary artery disease: What are the major knowledge gaps?

Translational platelet function investigations performed in the percutaneous coronary intervention (PCI)-treated population receiving clopidogrel have identified high platelet reactivity to ADP (HPR) as a major risk factor for both acute as well as long-term ischaemic event occurrence, including stent thrombosis. Recent studies have highlighted the relation of single nucleotide polymorphisms of genes involved in clopidogrel absorption and metabolism to reduced pharmacokinetic and pharmacodynamic responses to clopidogrel. CYP 2C19 loss-of-function (LoF) allele carriage has been associated with increased thrombotic risk in the PCI population. However, there is no information regarding the utility of platelet function testing to predict outcomes in patients with stable coronary artery disease and in medically managed patients with acute coronary syndromes. Additionally, few studies have included longitudinal assessment of platelet function to assess a potential time-dependent relation to ischaemic event occurrence and no phase-III antiplatelet-therapy trial has included a large enough platelet function sub-study to examine the relation between on-treatment platelet reactivity, bleeding, and ischaemic event occurrence. Therefore, futher studies are needed to delineate the role of platelet function testing across the spectrum of symptomatic coronary artery disease.