PLAVIX with Aspirin
Proven Efficacy with Aspirin Up to 1 Year1
CURE*–12,562 UA/NSTEMI patients1
- Reduced risk of MI, stroke, or CV death was demonstrated early and maintained long term, up to 1 year4
*The CURE trial (Clopidogrel in Unstable angina to prevent Recurrent Events) was a randomized, double-blind, placebo-controlled, multicenter study of 12,562 men and women from 482 centers in 28 countries presenting within 24 hours of acute chest pain or symptoms consistent with ischemia. Patients diagnosed with acute coronary syndrome (ACS) were randomized to PLAVIX 300 mg oral loading dose followed by PLAVIX 75 mg once daily or to placebo for up to 1 year (mean: 9 months). All patients received aspirin (75 mg–325 mg).
The primary outcome occurred in 9.3% of patients in the clopidigrel group and 11.4% in the placebo group.
In the co-primary combined end point of MI, stroke, CV death, or refractory ischemia, RRR was 14% (P=0.0005).
Only first events after randomization were counted in the composite end point.
PLAVIX with Aspirin Treatment Results
CV Risk Reduction in Patients With or Without a Stent
1,5
If a patient is to undergo surgery and an antiplatelet effect is not desired, discontinue PLAVIX 5 days prior to surgery.
- †With Intervention
- In the co-primary combined end point of nonfatal MI, stroke, CV death, or refractory ischemia, RRR was 15% (CI 0.76-0.96).5
- ‡No Intervention
- In the co-primary combined end point of nonfatal MI, stroke, CV death, or refractory ischemia RRR was 12% (CI 0.78-0.90).5
In the CURE Trial of 12,562 UA/NSTEMI patients, the rates of major and minor bleeding were higher in patients treated with PLAVIX + aspirin compared with placebo + aspirin1
| PLAVIX + aspirin in UA/NSTEMI |
% Incidence |
| CURE–up to 1 year1 |
PLAVIX + aspirin
n=6,259 |
Placebo + aspirin
n=6,303 |
P-value |
| Major bleeding* |
3.7 |
2.7 |
0.001 |
| Life-threatening |
2.2 |
1.8 |
0.13 |
| Fatal |
0.2 |
0.2 |
|
| 5 g/dL hemoglobin drop |
0.9 |
0.9 |
|
| Requiring surgical intervention |
0.7 |
0.7 |
|
| Hemorrhagic strokes |
0.1 |
0.1 |
|
| Requiring inotropes |
0.5 |
0.5 |
|
| Requiring transfusion (≥4 units) |
1.2 |
1.0 |
|
| Other major bleeding |
1.6 |
1.0 |
0.005 |
| Significantly disabling |
0.4 |
0.3 |
|
Intraocular bleeding with significant
loss of vision |
0.05 |
0.03 |
|
| Requiring 2-3 units of blood |
1.3 |
0.9 |
|
| Minor bleeding |
5.1 |
2.4 |
<0.001 |
*Major bleeding and other life-threatening bleeding.
Major bleeding rates were DOSE DEPENDENT on aspirin1
| Major bleeding by aspirin dose |
% Incidence |
| Aspirin dose1 |
PLAVIX + aspirin |
Placebo + aspirin |
| <100 mg |
2.6 |
2.0 |
| 100-200 mg |
3.5 |
2.3 |
| >200 mg |
4.9 |
4.0 |
View the CURE Trial — Full Reprint
PLAVIX is contraindicated in patients with active pathologic bleeding such as peptic ulcer or intracranial hemorrhage. Co-administering warfarin with PLAVIX increases the risk of bleeding. Co-administration of PLAVIX and NSAIDs increases the risk of gastrointestinal bleeding.1
The effectiveness of PLAVIX is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 (See WARNINGS and PRECAUTIONS: Drug Interactions.*). PLAVIX at recommended doses forms less of that metabolite and has a smaller effect on platelet function in patients who are CYP2C19 poor metabolizers. Poor metabolizers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with PLAVIX at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Tests are available to identify a patient's CYP2C19 genotype; these tests can be used as an aid in determining therapeutic strategy (See Clinical Pharmacology.*). Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers (See Dosage and Administration.*).
Important Safety Information
PLAVIX is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
PLAVIX is contraindicated in patients with hypersensitivity (eg, anaphylaxis) to clopidogrel or any component of the product. (See Adverse Reactions.*)
Avoid concomitant use of PLAVIX and drugs that inhibit CYP2C19 activity. Co-administration of PLAVIX with omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of PLAVIX if given concomitantly or if given 12 hours apart. (See Drug Interactions.*)
Thienopyridines, including PLAVIX, increase the risk of bleeding. If a patient is to undergo surgery and an antiplatelet effect is not desired, discontinue PLAVIX 5 days prior to surgery.
Avoid lapses in therapy, and if PLAVIX must be temporarily discontinued, restart as soon as possible. Premature discontinuation of PLAVIX may increase the risk of cardiovascular events.
In patients with recent TIA or stroke who are at high risk for recurrent ischemic events, the combination of aspirin and PLAVIX has not been shown to be more effective than PLAVIX alone, but the combination has been shown to increase major bleeding.
TTP, sometimes fatal, has been reported following use of PLAVIX, sometimes after a short exposure (<2 weeks). TTP is a serious condition that requires urgent treatment including plasmapheresis (plasma exchange).
Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction.
Co-administering warfarin with PLAVIX increases the risk of bleeding.
Co-administration of PLAVIX and NSAIDs increases the risk of gastrointestinal bleeding.
Nursing mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother.
*Please See the Full PLAVIX Prescribing Information, Including BOXED WARNING
Indications
For patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)] including patients who are to be managed medically and those who are to be managed with coronary revascularization, PLAVIX has been shown to decrease the rate of a combined end point of cardiovascular death, myocardial infarction (MI), or stroke as well as the rate of a combined end point of cardiovascular death, MI, stroke, or refractory ischemia.
For patients with ST-elevation myocardial infarction (STEMI), PLAVIX has been shown to reduce the rate of death from any cause and the rate of a combined end point of death, reinfarction, or stroke. The benefit for patients who undergo primary percutaneous coronary intervention is unknown.
The optimal duration of PLAVIX therapy in ACS is unknown.
For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, PLAVIX has been shown to reduce the rate of a combined end point of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.