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Three Part Question

In patients [undergoing percutaneous coronary intervention] is [Prasugrel better than Clopidogrel] in [preventing stent thrombosis.]

Clinical Scenario

A 50 yrs old man presents to the emergency department with central crushing chest pain, sweating and pain radiating to the left shoulder. ECG shows ST elevation in anterior leads. Your hospital is on take for PCI. You have referred him to the cardiology registrar informing that you have initiated the treatment with Aspirin, Clopidogrel and Fragmin. He tells you that he is taking this patient to the angiography suite in the next hour. He enquires if the department has Prasugrel, a new drug and tells you that Prasugrel is better than Clopidogrel for PCI with stent insertion. You wonder what this drug is and how this fares in comparison with Clopidogrel.

Search Strategy

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations April 30, 2010
Ovid MEDLINE(R), 1950 to April Week 3, 2010
Ovid OLDMEDLINE(R) 1947 to 1965

Exp Angioplasty, Transluminal, Percutaneous Coronary/ or percutaneous coronary angioplasty.mp. OR exp Angioplasty, Transluminal, Percutaneous Coronary/ or pci.mp
AND
prasugrel.mp.
AND
clopidogrel.mp.
limit to (English language and humans)

Search Outcome

Search Outcome – 68 papers.
1 relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Stephen D Wiviott 2009 USA	13,608 patients (10,074 with NSTEMI & unstable angina and 3534 with STEMI), who were all scheduled for PCI, were involved in the study across 707 sites and 30 countries between November 2004 and January 2007. Exclusion Criteria – Increased risk of bleeding, Anemia, Thrombocytopenia, History of intracranial pathology and any use of Thienopyridine within 5 days before enrolment. 60mg of Prasugrel or 300mg of Clopidogrel were administered in a double blind manner any time between randomization and up to one hour after PCI as a loading dose. After PCI patients received either 10mg of Prasugrel or 75mg of Clopidogrel with Aspirin. Efficacy comparison was performed on the basis of the time to the first event according to intention to treat principle. Patients were followed up for 15 months.	Randomised controlled trial	Primary Death from Cardiovascular causesnon fatal myocardial infarction or non fatal stroke.Key safety end point was major bleeding.	Death from Cardiovascular causes: Prasugrel-9.9% Clopidogrel-12.1%.Urgent target-vessel revascularization Prasugrel-2.5%Clopidogrel-3.7%.Odd’s Ratio-0.66 CI 0.54-0.81Stent Thrombosis:Prasugrel-1.1%Clopidogrel-2.4%Odd’s Ratio -0.48 CI 0.36-0.64 Major or minor TIMI bleeding-Prasugrel- 5% 3.8%.Odd’s Ratio -1.31Life threatening bleed-Prasugrel-1.45 Clopidogrel-0.9%Odd’s Ratio-1.52 CI 1.08-2.13	The study included patients with moderate to high risk coronary syndromes who were due for PCI on elective basis only. Patients with unstable angina or NSTEMI with symptoms lasting ten minutes or more but within 72 hours were also include in this study which is not the usual practice in the U.K. Study sponsored by Daiichi Sankyo and Eli Lilly who are marketing the drug.

Comment(s)

Prasugrel, an oral inhibhitor of platelet activation and aggregation is relatively a new drug which is being used in patients undergoing percutaneous coronary intervention. The major trial, TRITON-TIMI 38 showed that Prasugrel is better than Clopidogrel in preventing ischaemic events after PCI. Prasugrel also has increased risk of life threatening bleeding when compared to Clopidogrel. According to National Institute of Health and Clinical Excellence Prasugrel in combination with Aspirin is recommended as an option for preventing ischaemic events in people with acute coronary syndromes having Percutaneous Coronary Intervention only when 1. Immediate primary PCI for STEMI is necessary or 2. Stent thrombosis has occurred during Clopidogrel treatment or 3. The patient has diabetes mellitus. However further clinical trials are needed to confirm the efficacy and complications of Prasugrel.

Clinical Bottom Line

The combination of Prasugrel and Aspirin is more effective than a combination of Clopidogrel with Aspirin in the prevention of stent thrombosis after PCI

References

1. Stephen D. Wiviott et al for the TRITON–TIMI 38 Investigators new england journal of medicine November 2007 357;20