High Ticagrelor Loading Dose in STEMI
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 5/5/2014 |
| Start Date: | September 2013 |
| End Date: | March 2015 |
| Contact: | Dominick Angiolillo, MD, PhD |
| Email: | dominick.angiolillo@jax.ufl.edu |
| Phone: | 904-244-3933 |
Pharmacodynamic Profiles of Ticagrelor in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Different Loading Dosage Regimens
Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to
clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is
considered a first line therapy to be administered as soon as possible in ACS patients.
However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are
delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose
regimens of ticagrelor has therefore been advocated. The proposed investigation will have a
prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will
be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360
mg). Pharmacodynamic testing will be performed at several time points to test our study
hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet
inhibitory effects.
clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is
considered a first line therapy to be administered as soon as possible in ACS patients.
However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are
delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose
regimens of ticagrelor has therefore been advocated. The proposed investigation will have a
prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will
be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360
mg). Pharmacodynamic testing will be performed at several time points to test our study
hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet
inhibitory effects.
Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the
cornerstone of treatment for prevention of thrombotic events in patients with acute coronary
syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown
to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic
events, including cardiovascular mortality. Ticagrelor was recently approved for clinical
use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose.
Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS
patients, including those presenting with ST-elevation myocardial infarction (STEMI)
undergoing primary percutaneous coronary intervention (PCI). However, there are discordant
data on the onset of its antiplatelet effects in this particular setting. In particular, the
pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in
patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of
ticagrelor has therefore been advocated. However, if the administration of a higher
ticagrelor loading dose may overcome this limitation is still unknown and represents the aim
of our study. The proposed investigation will have a prospective, randomized, parallel
design in which STEMI patients undergoing primary PCI will be randomized to receive three
different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing
will be performed at several time points to test our study hypothesis that a higher loading
dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study
will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and
will help clinicians choose the most appropriate treatment to avoid complications related to
inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary
PCI.
cornerstone of treatment for prevention of thrombotic events in patients with acute coronary
syndromes (ACS). Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown
to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic
events, including cardiovascular mortality. Ticagrelor was recently approved for clinical
use in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose.
Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS
patients, including those presenting with ST-elevation myocardial infarction (STEMI)
undergoing primary percutaneous coronary intervention (PCI). However, there are discordant
data on the onset of its antiplatelet effects in this particular setting. In particular, the
pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are delayed in
patients with STEMI undergoing primary PCI. The use of higher loading dose regimens of
ticagrelor has therefore been advocated. However, if the administration of a higher
ticagrelor loading dose may overcome this limitation is still unknown and represents the aim
of our study. The proposed investigation will have a prospective, randomized, parallel
design in which STEMI patients undergoing primary PCI will be randomized to receive three
different loading dose of ticagrelor (180 mg, 270 mg and 360 mg). Pharmacodynamic testing
will be performed at several time points to test our study hypothesis that a higher loading
dose regiment will achieve more promptly enhanced platelet inhibitory effects. This study
will provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and
will help clinicians choose the most appropriate treatment to avoid complications related to
inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary
PCI.
Inclusion Criteria:
- Patients with ST-elevation myocardial infarction undergoing primary PCI.
- Age between 18 and 80 years old.
Exclusion Criteria:
- History of prior intracranial bleeding.
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,
ticagrelor) in past 30 days.
- Known allergies to aspirin or ticagrelor.
- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran,
rivaroxaban).
- Treatment with IIb/IIIa glycoprotein inhibitors.
- Fibrinolytics within 24 hours
- Known blood dyscrasia or bleeding diathesis.
- Known platelet count <80x106/mL.
- Known hemoglobin <10 g/dL.
- Active bleeding.
- Hemodynamic instability.
- Known creatinine clearance <30 mL/minute.
- Known severe hepatic dysfunction.
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker
protection.
- Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction
with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin,
nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and
telithromizycin.
- Pregnant females*.
- Women of childbearing age must use reliable birth control (i.e. oral
contraceptives) while participating in the study.
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