NICE approves prasugrel with limitation

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The United Kingdom’s National Institute for Health and Clinical Excellence (NICE) approved the anticlotting agent prasugrel a few days ago.

However, they recommended it only for limited use in certain higher-risk percutaneous coronary intervention patients on the UK’s National Health Service.

NICE determined that prasugrel be used only  in an emergency when there is no time for a loading dose of clopidogrel and in patients with diabetes or those who had a stent thrombosis while using clopidogrel.

NICE made the recommendation based on the risk of excessive bleeding with prasugrel. NICE also had reservations about the design of the TRITON trial submitted in support of the new drug.

The committee’s analysis states, “[I]n most aspects the design of the trial favored prasugrel.”  Patients in the clopidogrel group received half the dose generally used in the UK and did not get a pre-procedure loading dose.

The committee agreed that "there was considerable uncertainty about whether prasugrel was clinically superior to clopidogrel (Plavix) in terms of net clinical benefit.”

In a piece in the September 3 New England Journal of Medicine that coincided with NICE’s decision, Ellis F. Unger, MD, explained the US Food and Drug Administration’s (FDA) July decision to approve prasugrel with a warning. Dr Unger is from the FDA’s Office of New Drugs, Center for Drug Evaluation and Research.

He noted that the FDA review team believed “components of the primary end point represented irreversible tissue damage and concluded that the benefit of preventing such events is generally worth the risk of bleeding events that have no irreversible consequences.”

Dr Unger said that for each 1000 patients given prasugrel instead of clopidogrel, 24 end-point events—21 nonfatal myocardial infarctions and 3 cardiovascular deaths—were prevented.

The FDA required a boxed warning be included with prasugrel underscoring the increased risk for patients 75 years of age or older and for patients undergoing coronary artery bypass graft.

The FDA also required the manufacturer to perform a postmarketing study to investigate whether a platelet transfusion can reverse prasugrel-induced platelet inhibition. And the agency required the sponsors to collect baseline and subsequent data on cancer and prasugrel use in a large, ongoing clinical trial.

The FDA also concluded that the salt-to-base conversion experienced by prasugrel when it encounters a high-pH gastric environment, such as when the drug is administered with proton pump inhibitors, did not affect prasugrel’s performance.

Prasugrel is sold as Efient in Europe and Effient in the United States. Clopidogrel is sold as Plavix.

NICE is an independent organization that among other roles provides guidance on appropriate treatments and care within the UK’s National Health Service.

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