Optimal Switching Antiplatelet Regimen in Patients with Ticagrelor to a Thienopyridine in Korean Patients (SWAPT-K Study).

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Background East Asians treated with potent P2Y12 inhibitors, prasugrel or ticagrelor exhibit more potent platelet inhibition than clopidogrel. Whether half-dose de-escalation strategy would improve optimal platelet reactivity at maintenance in East Asian patients with acute coronary syndrome (ACS) remains uncertain. Method In de-escalation strategy single center study, eligible Korean ACS patients (n=96) were assigned to receive standard-dose ticagrelor (n=33), prasugrel (n=28), followed by half-dose reduction at 1 month for maintenance, and clopidogrel (n=35) as control. Platelet reactivity was measured by VerifyNow, light transmittance aggregometry (LTA) and multiple electrode aggregometry (MEA). The investigators aim to compare optimal platelet reactivity status (OPR, defined as 85–208 P2Y12 reaction unit [PRU] for VerifyNow (VN), 16%–47% for LTA and 19–46 U for MEA) among 3 different platelet function tests at 3 months post PCI. Results At 3 months, ticagrelor achieved significantly lower PRU (17 [6–51] vs. 95 [61–151] vs. 172 [111–204]) than prasugrel and clopidogrel, resulting OPR rate 10% vs. 57.7% vs. 60.0%, respectively. Similar results were observed at LTA method (2% [0–12] in ticagrelor vs. 18% [13–22] in prasugrel vs. 18% [11–30] in clopidogrel), with OPR rate 11.8% vs. 69.2% vs. 50.0%, respectively. However, platelet reactivity was similar by MEA method (16 [13–20] in ticagrelor vs. 17 [13–22] in prasugrel vs. 19 [14–28] in clopidogrel), with OPR rate 33.3% vs. 40.0% vs. 42.0%, respectively (all p>0.005). Among the three tests, resulting higher correlation between VN and LTA (r=0.745), MEA and LTA vs. MEA and VN showed lower correlations (r=0.412 and r=0.303). (Fig.) Conclusion In Korean ACS patients with half-dose de-escalation strategy after 1 month, OPR rate in ticagrelor is still rare during 3-month treatment by VN and LTA methods, however, prasugrel appears comparable to clopidogrel. VN/LTA might overestimate platelet function than MEA or MEA underestimate OPR rate than VN/LTA. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): National Research Foundation of Korea

Current guidelines recommend dual antiplatelet therapy (DAPT) that includes aspirin and the platelet P2Y12 ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin.1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI.2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity.2,3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel and …

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

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

HomeCirculationVol. 141, No. 14Response by Park and Park to Letter Regarding Article, “Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Park and Park to Letter Regarding Article, “Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial” Duk-Woo Park, MD and Seung-Jung Park, MD Duk-Woo ParkDuk-Woo Park Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Search for more papers by this author and Seung-Jung ParkSeung-Jung Park https://orcid.org/0000-0002-9187-5405 Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Search for more papers by this author Originally published6 Apr 2020https://doi.org/10.1161/CIRCULATIONAHA.120.045963Circulation. 2020;141:e741–e742In Response:The TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management) trial is an open-label, multiple-center, randomized, controlled trial with blinded event adjudication in patients with acute coronary syndromes intended for early invasive management. A total of 800 patients presenting with acute coronary syndromes randomly received either ticagrelor (180 mg, followed by 90 mg twice daily) or clopidogrel (600 mg, followed by 75 mg daily).1 The primary end point was PLATO (Platelet Inhibition and Patient Outcomes) clinically significant bleeding at 12 months. There were significantly higher bleeding rates as assessed by PLATO and several other bleeding scores and clinically significant, major, and fatal bleeding in patients receiving ticagrelor. The differences between treatment groups were driven by nonprocedure or noncoronary artery bypass grafting-related bleeding. The ischemic end point of cardiovascular death, myocardial infarction, and stroke trended toward higher events in ticagrelor-treated patients than in clopidogrel-treated patients. A majority of events occurred early; however, an analysis censored at 30 days revealed similar results. This finding of increased bleeding without a suggestion of efficacy is dissimilar to PLATO and, if real, could be important in Korean patients and potentially others of Asian descent.Regarding this issue, Chen et al raised several important issues. A post hoc analysis of the PLATO trial suggest that the high dose of aspirin, 300–325 mg (53.6%), in the United States compared with the rest of the world (1.7%) was the only factor to explain the regional interaction that ticagrelor was less effective and potentially more harmful than clopidogrel. However, in the TICAKOREA, low-dose aspirin (100 mg daily) has been recommended on the basis of the current guideline recommendations. Although ticagrelor monotherapy with short duration of aspirin was tested in high-risk or all-comer patients in the recent trials,3,4 further studies are required to assess the safety and efficacy of this tailored therapy with aspirin omission in the East Asian population with differential bleeding and ischemic propensity compared with the Western population. Second, we did not find any violations of proportional assumption in several analyses in the entire population and in major subgroup analyses as shown in Figure 4.1 Overall findings were mostly consistent in key subgroup analyses including age category and important clinical covariates. Third, in sensitivity analysis (supplemental Table I in the article), hazard ratios were consistent with the primary results, further adjusting hypertension and chronic lung disease, which were statistically different between 2 groups at baseline.1Kim et al also suggested several interesting issues regarding our trial. Current guidelines recommend that inhibitors of the adenosine diphosphate receptor P2Y12 should be administered as soon as possible for patients with acute coronary syndromes; this strategy was also applied in our trial. Although concerns regarding increased access site bleeding with pretreatment of P2Y12 inhibitors was raised, the hazard ratio with ticagrelor compared with clopidogrel was much higher with respect to nonprocedure/coronary artery bypass grafting–related bleeding than procedure-related bleeding in our trial. Current European guidelines, but not US guidelines, recommend all-comer use of proton-pump inhibitors with dual antiplatelet therapy (Class 1 and Level of Evidence B).5 However, compelling evidence supporting the routine use of proton-pump inhibitors for all-comer patients receiving dual antiplatelet therapy is still limited,6 and also such strategy is not permitted in our practice because of the reimbursement policy in Korea. Last, although observational studies provided important insights about real-world clinical effectiveness and safety, overall findings were less consistent and were substantially variable7; therefore, it should be confirmed or refuted through randomized, controlled trials. As such, reduced dosing and tailored therapy with an escalation/deescalation strategy of potent P2Y12 inhibitors in the East Asian population should be supported by large randomized controlled trials.DisclosuresNone.Footnoteshttps://www.ahajournals.org/journal/circ

HomeCirculationVol. 141, No. 14Letter by Kim et al Regarding Article, “Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Kim et al Regarding Article, “Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial” Yongcheol Kim, MD, Thomas W. Johnson, MBBS, MD and Myung Ho Jeong, MD, PhD Yongcheol KimYongcheol Kim https://orcid.org/0000-0001-5568-4161 Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine and Cardiovascular Center, Yongin Severance Hospital, Korea (Y.K.). Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea (Y.K., M.H.J.). Search for more papers by this author , Thomas W. JohnsonThomas W. Johnson Department of Cardiology, Bristol Heart Institute, United Kingdom (T.W.J.). Search for more papers by this author and Myung Ho JeongMyung Ho Jeong Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea (Y.K., M.H.J.). Search for more papers by this author Originally published6 Apr 2020https://doi.org/10.1161/CIRCULATIONAHA.119.044256Circulation. 2020;141:e737–e738To the Editor:We read with interest the recently published article by Park et al1 evaluating the comparison of clinical safety and efficacy between ticagrelor and clopidogrel in Korean patients with acute coronary syndrome. It is evident that the use of standard-dose ticagrelor is associated with a higher incidence of clinically significant bleeding complications, without a reduction in the incidence of ischemic events, in comparison with clopidogrel use at a 12-month end point. After reading this article carefully, we have some comments for the kind consideration of the authors.The authors acknowledge that preloading with antiplatelet therapy is supported by guidelines; however, it has been shown that this can be associated with an increased risk of bleeding, most commonly related to access site.2 Femoral access was frequently adopted (47.5% of the cohort), so it is not surprising that procedure-related bleeding contributed to 27.3% (18/66) of all clinically significant bleeds. Furthermore, contemporary guidance provides a class 1 level B recommendation for the use of proton pump inhibitors, but the use of proton pump inhibitors was very limited in the current study (2.5%). It is likely that the risk of gastrointestinal bleeding could have been minimized by the combined use of proton pump inhibitors with dual antiplatelet therapy.Enrollment of 800 patients from 10 major centers over 3 years suggests significant selection bias that was not addressed in the discussion. Application of these results to an unselected population must be undertaken with caution. The efficacy and safety of P2Y12 inhibitors in Korean patients presenting with acute myocardial infarction have been tested previously with the use of standard-dose ticagrelor (180 mg loading dose, 90 mg twice daily) and prasugrel (60 mg loading dose, 10 mg/d). Consistent with the findings in this contemporary study, use of potent P2Y12 inhibitors was associated with a significantly higher incidence of bleeding events without a reduction of ischemic events in comparison with clopidogrel.3 In a European population, downtitration of potent P2Y12 inhibition at one month resulted in an important reduction in bleeding.4 However, a landmark analysis of the current cohort at 30 days highlights that the difference in bleeding is observed early. Recent data from Japan5 have highlighted the effective use of reduced-dose potent P2Y12 inhibitors (3.75 mg prasugrel once daily) in a heterogeneous population of stable patients and patients with acute coronary syndrome. Large-scale studies in East Asian populations clearly are required to establish the appropriate dosing, duration of treatment, and possible deescalation of potent P2Y12 inhibition.DisclosuresNone.Footnoteshttps://www.ahajournals.org/journal/circ

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.

Background: The optimal dosing of novel oral P2Y₁₂ receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y₁₂ flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y₁₂ receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

BackgroundClopidogrel nonresponsiveness is a prognostic marker after percutaneous coronary intervention. Prasugrel and ticagrelor provide a better platelet inhibition and represent the first‐line antiplatelet treatment in acute coronary syndrome. We sought to assess the prognostic impact of high platelet reactivity (HPR) and the potential clinical benefit of a “tailored” escalated or changed antiplatelet therapy in patients with chronic total occlusion.Methods and ResultsFrom Florence CTO‐PCI (chronic total occlusion‐percutaneous coronary intervention) registry, platelet function assessed by light transmission aggregometry, was available for 1101 patients. HPR was defined by adenosine diphosphate test ≥70% and optimal platelet reactivity by adenosine diphosphate test <70%. The endpoint of the study was long‐term cardiac survival. Patients were stratified according to light transmission aggregometry results: optimal platelet reactivity (82%) and HPR (18%). Means for the adenosine diphosphate test were 44±16% versus 77±6%, respectively. Three‐year survival was significantly higher in the optimal platelet reactivity group compared with HPR patients (95.3±0.8% versus 86.2±2.8%; P<0.001). With the availability of new P2Y12 inhibitors, a deeper platelet inhibition (46±17%) and similar survival to the optimal platelet reactivity group were achieved in patients with HPR on clopidogrel therapy after escalation. Conversely, HPR on clopidogrel therapy “not switched” was associated with cardiac mortality (hazard ratio 2.37; P=0.003) after multivariable adjustment.ConclusionsHPR on treatment could be a modifiable prognostic marker by new antiaggregants providing a deeper platelet inhibition associated with clinical outcome improvement in complex chronic total occlusion patients. A “tailored” antiplatelet therapy, also driven by the entity of platelet inhibition, could be useful in these high risk setting patients.

Background Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after percutaneous coronary intervention (PCI) to reduce the risk of adverse cardiovascular events. Currently, an increasing number of PCIs are performed in patients with complex anatomic features, which is associated with a higher risk of ischemic events. Potent P2Y12 inhibitors such as prasugrel and ticagrelor provide more rapid, uniform and potent platelet inhibition than clopidogrel. However, the balance between enhanced antithrombotic efficacy and the potential increase in bleeding risk with potent P2Y12 inhibitors in the setting of complex PCI remains uncertain. Purpose This systematic review and meta-analysis aimed to assess the effectiveness and safety of DAPT strategies using potent P2Y12 inhibitors (prasugrel or ticagrelor) versus clopidogrel in patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) undergoing complex PCI. Methods PubMed, Scopus and Cochrane databases were searched for randomized controlled trials (RCTs) and observational studies comparing ticagrelor or prasugrel versus clopidogrel in patients undergoing complex PCI. Complex PCI was defined according to criteria commonly used in the literature, including coronary bifurcations, chronic total occlusions, severe calcifications requiring atherectomy and left main disease. All outcomes were assessed at the 1-year follow-up. We pooled risk ratios (RR) with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed using the I² statistic. Results We included one randomized controlled trial and nine observational studies, encompassing a total of 37,365 patients undergoing complex PCI. Among these, 11,078 received dual antiplatelet therapy with potent P2Y12 inhibitors (8,450 with ticagrelor and 2,628 with prasugrel), while 26,287 patients were treated with clopidogrel-based DAPT. Treatment with potent P2Y12 inhibitors was associated with significantly lower all-cause mortality (RR 0.52; 95% CI 0.36–0.76; p=0.0007) and cardiovascular death (RR 0.61; 95% CI 0.48–0.78; p&amp;lt;0.0001) compared to clopidogrel. No significant differences were observed between groups in the incidence of myocardial infarction (RR 0.80; 95% CI 0.58–1.10; p=0.17), stroke (RR 0.71; 95% CI 0.33–1.53; p=0.38), target vessel revascularization (RR 0.86; 95% CI 0.58–1.26; p=0.44) and stent thrombosis (RR 0.70; 95% CI 0.43–1.15; p=0.16). The risk of major bleeding did not differ significantly between the treatment groups (RR 0.93; 95% CI 0.71–1.20; p=0.57). Conclusion In patients undergoing complex PCI, DAPT with potent P2Y12 inhibitors was associated with a significant reduction in all-cause mortality and cardiovascular death, without an increased risk of major bleeding.ALL- CAUSE MORTALITY AND C.V. DEATH MYOCARDIAL INFARCTION AND MAJOR BLEEDING

Efficacy and safety of potent platelet P2Y12 receptor inhibitors in elderly versus nonelderly patients with acute coronary syndrome: A systematic review and meta-analysis

CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome

The only reason P2Y12 inhibitors are administered in addition to aspirin is to improve the prevention of thrombosis. The clinical efficacy of adding clopidogrel to aspirin as a secondary prevention strategy in patients with high-risk coronary artery disease is well established.1 There are no effects of clopidogrel on any receptor other than P2Y12 to explain the magnitude of the clinical benefit. All of the established clinical effects are attributed to reduced platelet responsiveness to ADP.2 Therefore, the patient with inadequate P2Y12 inhibition determined by ex vivo testing logically has an increased risk for thrombosis. Persistent ischemic event occurrence and the irrefutable demonstration of clopidogrel antiplatelet response variability are 2 potent arguments against the widely practiced nonselective or one-size-fits-all strategy of administering clopidogrel therapy. Observational studies conducted in thousands of patients have led to an international consensus that high on-treatment platelet reactivity (HPR) to ADP is a major risk factor for post–percutaneous coronary intervention (PCI) ischemic event occurrence.3,4 Moreover, the recent 2011 American and European guidelines have given a Class IIb recommendation for platelet function testing or genotyping if the results of testing may alter management.5–7 Furthermore, the Society of Thoracic Surgeons gave a Class IIb recommendation for platelet function testing to determine the timing of surgery in patients on clopidogrel therapy (Level of Evidence C).8 These recommendations for personalizing antiplatelet therapy are unprecedented and acknowledge that a large body of data has accrued demonstrating the relation of HPR to ischemic risk in the PCI-treated patient. Finally, the evidence of diminished effectiveness of clopidogrel in poor metabolizers (those having 2 loss-of-function [LoF] cytochrome P450 [ CYP ] 2C19 alleles) has been recognized by the Food and Drug Administration (FDA) boxed warning about treatment with clopidogrel.9 Response by Krishna …

PHARMACODYNAMIC EVALUATION OF THE PLATELET ANTIAGGREGANT EFFECT OF SWALLOWED TICAGRELOR AGAINST CHEWED TICAGRELOR IN PATIENTS WITH ACUTE CORONARY SYNDROME. TICA-MASTICA-SICA TRIAL