Leaders in Pharmaceutical Business Intelligence (LPBI) Group

HOUSTON, TX — Nearly one in five patients treated withprasugrel (Effient, Lilly/Daiichi Sankyo) in the PINNACLEregistry is receiving the drug inappropriately or for a nonrecommended indication, according to a new analysis^[1].

Among more than 27 500 patients treated with prasugrel at 123 US practices, almost 14% had a documented prior history of stroke or transient ischemic attack (TIA): two conditions singled out in a boxed warning in the drug packaging. According to that labeling, prior stroke or TIA can increase the risk of bleeding.

An additional 4.4% of patients in the analysis were taking prasugrel despite being 75 years of age or older with no diabetes or prior MI, the analysis suggests. Dr Ravi Hira(Baylor College of Medicine, Houston, TX) and colleagues published their findings last month in an online research letter in the Journal of the American College of Cardiology.

Current ACC/AHA guidelines for STEMI and unstable angina/NSTEMI give prasugrel a class I recommendation for use at the time of PCI but advise against its use (class III) in patients with a prior TIA or stroke. In TRILOGY ACS , prasugrel was no better than clopidogrel in reducing CV events in patients with ACS who were not treated invasively, and as such, the drug is not approved for medically managed patients.

In an interview with heartwire , Hira said he and his coinvestigators had their interest piqued after seeing a number of non-ACS patients or patients with a history of stroke/TIA referred to their practices. “That got us thinking, let’s see if we can assess the rate of inappropriate or off-label use” in a larger population, he said.

Practice patterns in inappropriate prasugrel use varied significantly between hospitals across the sample, Hira et al note, although there were no differences seen according to patient age or gender. Inappropriate or off-label prasugrel use was more common in patients with comorbidities, including diabetes, hypertension, dyslipidemia, atrial fibrillation, heart failure, peripheral artery disease (PAD), and CABG, they note.

That hints at the possibility that physicians are opting to use a more potent antiplatelet drug in patients whom they fear are at higher risk of ischemic events, Hira commented.

But clearly not all practitioners have the same concerns with inappropriate use, ranging from 0% to 90% within individual practices. Differences at the practice level mean that two “identical” patients treated at two randomly chosen practices would receive radically different care, with the risk of inappropriate prasugrel treatment being as much as 189% increased at one facility vs another.

A further problem identified by the investigators was use of triple therapy—aspirin, warfarin, and prasugrel. In PINNACLE, triple therapy was seen in 15.4% of the sample, despite the fact that the use of prasugrel on top of warfarin and aspirin has not been studied.

“It’s possible that triple therapy with prasugrel in this group, even when appropriate, may lead to increased rates of major bleeding and offset any anti-ischemic benefit of prasugrel,” the authors write.

PINNACLE is an outpatient registry, so one possibility is that patients are being placed on prasugrel during hospital admission, not by the cardiology practices enrolled in PINNACLE, suggesting “there may be a disconnect between inpatient and outpatient care,” Hira said. He and his colleagues also could not review the reasons underlying a physician’s decision to put a patient on prasugrel instead of clopidogrel or the other newer antiplatelet drug, ticagrelor (Brilinta, AstraZeneca). Moreover, stroke and TIA were self-reported in the study.

Hira points out that there are no warnings against the use of ticagrelor in patients with prior TIA or stroke (although it is contraindicated in patients with a history of intracranial hemorrhage). PINNACLE is now collecting information on ticagrelor use. He and his colleagues hope to analyze this newer data to also assess inappropriate use of ticagrelor as well as the drivers of any decision to use prasugrel over ticagrelor and vice versa.

Hira had no conflicts of interest. Disclosures for the coauthors are listed in the article.