Table 1

Studies Linking High On-Treatment Platelet Reactivity to ADP and Clopidogrel Nonresponsiveness to Post-PCI Adverse Clinical Event Occurrence

Study (Ref. #)Patients (n)TreatmentMethodsDefinitionClinical Relevance
Barragan et al. (58)PCI (46)250 mg qd TLP or CLP 75 mg qdVASP-PRI>50% VASP-PRI↑ ST
Gurbel et al. (55)Elective PCI (192)300-mg LD + 75 mg qd CLP +/– EPT5-μmol/l ADP-LTAHPR = 75th percentile post-PCI aggregation↑ 6-month post-PCI events, OR: 2.7
Matetzky et al. (59)PCI/STEMI (60)300-mg LD + 75 mg qd CLP +/– EPT5-μmol/l ADP-LTAReduction in platelet aggregation Upper quartile↑ 6-month cardiac events
Gurbel et al. (60)Elective PCI (120)300-mg LD CLP +/– EPT5-μmol/l ADP-LTAMean periprocedural platelet aggregation >50%↑ Periprocedural myonecrosis
Gurbel et al. (61)Elective PCI (200)300-/600-mg LD CLP +/– EPT5-μmol/l ADP-LTAMean periprocedural platelet aggregation >40%↑ Periprocedural myonecrosis
Bliden et al. (54)Elective PCI (100)75 mg qd CLP5-μmol/l ADP-LTA>50% platelet aggregation↑ 1-yr post-PCI events
Lev et al. (43)Elective PCI (150)300-mg CLP LD5- and 20-μmol/l ADP-LTABaseline—post-treatment aggregation ≤10%↑ Periprocedural myonecrosis
Blindt et al. (62)High risk for ST/PCI (99)75 mg qd for 6 monthsVASP-PRI (72–96 h after stenting)>48% PRI (ROC)↑ 6-month ST
Cuisset et al. (63)NSTEMI/ACS/PCI (190)600-mg CLP LD >6 h before PCI10-μmol/l ADP-LTA VASP-PRIHPR >70% post-treatment LTA↑ Periprocedural myonecrosis
Frere et al. (64)NSTEMI/ACS/PCI (195)600-mg CLP LD >6 h before PCI10-μmol/l ADP-LTAHPR (ROC) >70% post-treatment LTA >53% VASP-PRI↑ 30-day post-PCI events MACE + stroke
Geisler et al. (65)CAD/PCI (379)600-mg CLP LD >6 h before PCI20-μmol/l ADP-LTAClopidogrel low responders = <30% platelet inhibition↑ 3-month MACE and death OR: 4.9
Geisler et al. (66)CAD/PCI (1,092)600-mg CLP LD >6 h before PCI + 75 mg qd
  • 20-μmol/l ADP-LTA

  • Residual aggregation measured after 5 min

Upper quartile↑ 30-day MACE
Hochholzer et al. (67)Elective PCI (802)600-mg CLP LD >2 h before PCI + 75 mg qd5-μmol/l ADP-LTA Residual aggregation measured after 5 minPlatelet aggregation above median↑ 30-day MACE OR: 6.7
Price et al. (68)PCI (380)600-mg CLP LD >12 h before PCI or 75 mg qd >5 daysVerifyNow P2Y12 assayHPR = post-treatment ≥235 PRU (ROC)↑ 6-month post-PCI events including ST
Gurbel et al. (69)Elective PCI (297)300-/600-mg LD/75 mg qd CLP +/– EPT5- and 20-μmol/l ADP-LTA
  • HPR = post-procedural (ROC)

  • >46% 5-μmol/l ADP

  • >59% 20-μmol/l ADP

  • ↑ 2-yr ischemic events

  • 5-μmol/l ADP OR: 3.9

  • 20-μmol/l ADP OR: 3.8

Gurbel et al. (70)Stenting (120)75-mg qd CLP >5 days5- and 20-μmol/l ADP-LTA
  • HPR >75th percentile of platelet reactivity

  • 5-μmol/l ADP = 50%

  • 20-μmol/l ADP = 65%

↑ ST
Buonamici et al. (71)PCI/DES (804)600-mg LD + 75 mg qd for 6 months10-μmol/l ADP-LTAHPR ≥70% aggregation↑ ST HR: 3.08
Bonello et al. (72)PCI/stenting (144)300-mg LD >24 hVASP-PRI>50% PRI (ROC)↑ 6-month post-PCI MACE
Cuisset et al. (73)PCI/SA (120)600-mg LD ≥12 h before PCIVerifyNow P2Y12 assay↑ Platelet reactivity↑ Post-PCI myonecrosis
Migliorini et al. (74)PCI/DES/ULMD (215)600-mg LD + 75 mg qd for 12 months10-μmol/l ADP-LTAHPR ≥70% aggregation
  • ↑ 3-yr cardiac death and ST

  • HR CV death: 3.82

  • HR ST: 3.69

Marcucci et al. (75)PCI/ACS (683)600-mg LD + 75 mg qdVerifyNow P2Y12 assayHPR ≥240 PRU
  • 12-month ischemic event

  • HR CV death: 2.55

  • HR nonfatal MI: 3.36

Bonello et al. (76)PCI/stenting (162)600 mg repeated dose until PRI <50%VASP-PRI<50% VASP-PRI↓ 1-month ischemic event
Bonello et al (77)PCI/stenting (214)600-mg repeated dose until PRI <50%VASP-PRI<50% VASP-PRI↓ Early ST and MACE (OR: 9.4)
Valgimigli et al. (78)Elective PCI (1,277)600-mg LD before PCIVerifyNow aspirin and P2Y12 assay>235 PRU >550 ARU↑ Post-PCI myonecrosis
Patti et al. (79)PCI (160)600-mg LD or 75 mg qd >5 daysVerifyNow P2Y12 assayHPR ≥240 PRU (Pre-PCI)↑ 1-month major cardiovascular event occurrence
Sibbing et al. (80)PCI/DES (1,608)600-mg LD before PCI6.4-μmol/l ADP Multiplate analyzerUpper quintile (>416 AU/min) (ROC)↑ 1-month definite ST (OR: 9.4)
Cuisset et al. (81)NSTEMI/stenting (598)600-mg LD ≥12 h before PCI10-μmol/l ADP-LTA VASP-PRI>67% aggregation (ROC)↑ ST
Breet et al. (82)Elective PCI (1,069)
  • 75-mg qd >5 days

  • 300-mg LD >1 day

  • 600-mg LD

  • 20-μmol/l ADP-LTA

  • VerifyNow P2Y12

  • 20-μmol/l ADP Plateletworks

  • Before PCI

  • >42.9% 5-μmol/l ADP (ROC)

  • >64.5% 20-μmol/l ADP

  • >236 PRU

  • 80.5% Plateletworks

  • OR for 1-yr death, MI, ST, and stroke 5-μmol/l ADP: 2.09 20-μmol/l ADP: 2.05

  • VerifyNow: 2.53

  • Plateletworks: 2.22

ACS = acute coronary syndromes; ADP = adenosine diphosphate; ARU = aspirin resistance units; AU = arbitrary aggregation units; CAD = coronary artery disease; CLP = clopidogrel; CV = cardiovascular; DES = drug-eluting stent; EPT = eptifibatide; HPR = high on-treatment platelet reactivity; HR = hazard ratio; LD = loading dose; LTA = light transmittance aggregometry; MACE = major adverse cardiac events; MI = myocardial infarction; NSTEMI = non–ST-segment elevated myocardial infarction; OR = odds ratio; PCI = percutaneous intervention; PRU = P2Y12reaction units; qd = once daily; ROC = receiver-operator characteristic curve; SA = stable angina; ST = stent thrombosis; STEMI = ST-segment elevated myocardial infarction; TLP = ticlopidine; ULMD =unprotected left main disease; VASP-PRI = vasodilator stimulated phosphoprotein—platelet reactivity index.