TRITON-TIMI 38 CLINICAL TRIAL DESIGN
Effient® (prasugrel) was studied in TRITON-TIMI 38, a head-to-head trial vs clopidogrel
The objective of the TRITON-TIMI 38 clinical trial was to evaluate the efficacy and safety of Effient® (prasugrel) plus aspirin (ASA) compared with clopidogrel plus ASA in patients with moderate- to high-risk ACS who were to be managed with PCI.1,2
ACS (UA/NSTEMI or STEMI) and planned PCI1,2
Median duration of follow-up: 14.5 months
Effient + ASA
60-mg LD/10-mg MD
Clopidogrel + ASA
300-mg LD/75-mg MD
Primary efficacy endpoint: Composite of CV death, nonfatal MI, or nonfatal stroke
Bleeding-related safety endpoints: TIMI major* or minor† bleeding
*Intracranial hemorrhage or clinically overt bleeding associated with a fall in hemoglobin ≥5 g/dL. †Clinically overt bleeding associated with a fall in hemoglobin of ≥3 g/dL but <5 g/dL.
- 74% were UA/NSTEMI patients (n=10,074) and approximately one-fourth (26%) were STEMI patients (n=3534)1,2
- In TRITON-TIMI 38, the LD of clopidogrel was delayed relative to the placebo-controlled trials that supported its approval for ACS2
- Aspirin was administered upon presentation. Effient or clopidogrel was not administered until coronary anatomy was established in UA/NSTEMI patients and in STEMI patients presenting more than 12 hours after symptom onset. In STEMI patients presenting within 12 hours of symptom onset, the loading dose of Effient or clopidogrel was administered at the time of diagnosis, although most received Effient at the time of PCI. In TRITON-TIMI 38, 29% of STEMI-PCI patients were given the loading dose of Effient prior to PCI3
- For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial2
SELECTED SAFETY: EFFIENT INCREASED THE RISK OF TIMI MAJOR OR MINOR BLEEDING VS CLOPIDOGREL
Effient can cause significant, sometimes fatal, bleeding. Overall rates of non-CABG TIMI major or minor bleeding were significantly higher with Effient plus ASA (4.5%) compared with clopidogrel plus ASA (3.4%). The rates of fatal bleeding were 0.3% with Effient plus ASA and 0.1% with clopidogrel plus ASA. In patients who underwent CABG (N=437), the rates of CABG-related TIMI major or minor bleeding were 14.1% with Effient plus ASA and 4.5% with clopidogrel plus ASA.
References: 1. Wiviott SD, Braunwald E, McCabe CH, et al; for the TRITON-TIMI 38 Investigators. N Engl J Med. 2007;357:2001-2015. 2. Effient® (prasugrel) prescribing information. Daiichi Sankyo, Inc. and Eli Lilly and Company. 3. Data on file: #EFF20150721a: DSI/Lilly.
Effient® (prasugrel) is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows:
- Patients with unstable angina (UA) or non–ST-elevation myocardial infarction (NSTEMI)
- Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI
The loading dose (LD) of Effient is 60 mg and the maintenance dose (MD) is 10 mg once daily. Effient is available in 5-mg and 10-mg tablets.
IMPORTANT SAFETY INFORMATION
WARNING: BLEEDING RISK
Effient® (prasugrel) can cause significant, sometimes fatal, bleeding.
Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke.
In patients ≥75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction [MI]) where its effect appears to be greater and its use may be considered.
Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery.
Additional risk factors for bleeding include:
- body weight <60 kg
- propensity to bleed
- concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs])
Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient.
If possible, manage bleeding without discontinuing Effient. Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events.
- Effient is contraindicated in patients with active pathological bleeding, such as from a peptic ulcer or intracranial hemorrhage (ICH), or a history of transient ischemic attack (TIA) or stroke, and in patients with hypersensitivity to prasugrel or any component of the product
WARNINGS AND PRECAUTIONS
- Patients who experience a stroke or TIA while on Effient generally should have therapy discontinued. Effient should also be discontinued for active bleeding and elective surgery
- Premature discontinuation of Effient increases risk of stent thrombosis, MI, and death
- Thrombotic thrombocytopenic purpura (TTP), a rare but serious condition that can be fatal, has been reported with Effient, sometimes after a brief exposure (<2 weeks), and requires urgent treatment, including plasmapheresis
- Hypersensitivity, including angioedema, has been reported in patients receiving Effient, including patients with a history of hypersensitivity reaction to other thienopyridines
- Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction