Testing platelet Reactivity In patients underGoing elective stent placement on clopidogrel to Guide alternative thErapy with pRasugrel - TRIGGER-PCI


The TRIGGER-PCI trial sought to study whether treatment with prasugrel in nonresponders to clopidogrel would be associated with an improvement in platelet reactivity testing on follow-up.


Prasugrel would be superior to clopidogrel in patients who were noted to be nonresponders to clopidogrel on day 1 following uneventful percutaneous coronary intervention (PCI) (defined as P2Y12 reaction units [PRU] >208 units on the VerifyNow assay).

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Successful DES-PCI in patients with stable coronary artery disease and clinical indication for PCI
  • Clopidogrel 600 mg loading dose between 24 hours before, and the time of PCI + 75 mg maintenance dose in the morning after PCI

    Number of screened applicants: 3,525
    Number of enrollees: 423
    Duration of follow-up: 6 months


  • Patients with ST-elevation myocardial infarction (STEMI)/non-STEMI within 14 days
  • Body weight <60 kg
  • Glycoprotein IIb/IIIa inhibitors eptifibatide or tirofiban within 24 hours before or during PCI, or abciximab within 10 days before or during PCI
  • Daily nonsteroidal anti-inflammatory drug use
  • Contraindication to aspirin or any of the study drugs
  • Patients with known major complications after PCI

Primary Endpoints:

  • Cardiovascular death or myocardial infarction at 6 months

Secondary Endpoints:

  • PRU testing at days 90 and 180
  • Non-CABG TIMI major bleeding

Drug/Procedures Used:

All patients received a loading dose (LD) of clopidogrel 600 mg along with aspirin, at least 250 mg (intravenous or oral), between 24 hours before and at the time of PCI. Patients randomized to prasugrel received a 60 mg LD, followed by 10 mg daily as maintenance dose (MD). Patients in the clopidogrel arm received 75 mg daily of clopidogrel.

Concomitant Medications:

Statin (78%), proton pump inhibitor (21%), beta-blockers (72%)

Principal Findings:

Of all patients tested, 19% had PRU >208 and were eligible for enrollment in this trial. The trial randomized 423 patients, 212 to prasugrel and 211 to clopidogrel, but only 236 patients had completed 6-month follow-up, when the study was terminated early due to futility. Baseline characteristics were fairly similar between the two arms. Baseline PRUs were similar between the prasugrel and clopidogrel arms (245 vs. 249). About 15% were smokers, 42% were diabetic, 27% had prior myocardial infarction, and 21% were on proton pump inhibitors.

Mean number of drug-eluting stents (DES) was 1.9, with a total stent length of about 19 mm. About 51% of the stents were Xience V/Promus (everolimus-eluting stent), 28% were Cypher (sirolimus-eluting stent), and 9% were Endeavor (zotarolimus-eluting stent). Baseline PRUs were similar between the prasugrel and clopidogrel arms. At days 90 and 180, there was a significant improvement in PRUs in the prasugrel arm as compared with the clopidogrel arm (p < 0.001 for both time points). The proportion of patients with PRUs >208 was significantly lower in the prasugrel arm at both 90 days (5.9% vs. 70.4%, p < 0.001) and 180 days (5.8% vs. 70.8%, p < 0.001).

The primary composite efficacy endpoint of cardiovascular death or myocardial infarction was similar between the two arms (0% vs. 0.5%, p > 0.05). Rehospitalization for cardiac ischemia (0.9% vs. 1.9%) and strokes (0% vs. 0.5) (p > 0.05 for both) were similar. There were no episodes of stent thrombosis in either arm. Noncoronary artery bypass grafting (CABG) Thrombolysis in Myocardial Infarction (TIMI) major bleeding was numerically higher in the prasugrel arm (1.4% vs. 0.5%, p = 0.52).


The results of this small trial confirm that prasugrel results in improvements in platelet reactivity as compared with continuation clopidogrel in patients with defined high on-clopidogrel platelet reactivity (>208 PRU by VerifyNow P2Y12 test). No differences in clinical outcomes were seen, although the trial was grossly underpowered to study such differences. The overall yield for the trial may have been higher if patients with acute myocardial infarction were also included. 

Although appealing, platelet reactivity testing-guided antiplatelet management has so far not been shown to improve clinical outcomes. The large GRAVITAS trial had demonstrated no improvement in clinical outcomes with high-dose clopidogrel (150 mg/day) when compared with standard-dose clopidogrel (75 mg/day) despite an improvement in hypo-responsiveness.


Trenk D, Stone GW, Gawaz M, et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study. J Am Coll Cardiol 2012;Apr 18:[Epub ahead of print].

Presented by Dr. Dietmar Trenk at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2011), San Francisco, CA, November 9, 2011.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Follow-Up Studies, Drug-Eluting Stents, Thiophenes, Ticlopidine, Blood Platelets, Piperazines, Sirolimus, Proton Pump Inhibitors, Percutaneous Coronary Intervention, Thrombosis, Medical Futility, Diabetes Mellitus

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