PINNACLE Patients: Inappropriate Prasugrel (Effient, Lilly/Daiichi Sankyo) Use in “One in Five”: Prior Stroke or TIA can increase the risk of Bleeding
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 7/4/2021
Prasugrel outperforms ticagrelor among PCI patients
Prasugrel is associated with better outcomes than ticagrelor when treating acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI), according to new findings published in JAMA Cardiology.
The study’s authors evaluated data from the ISAR-REACT 5 trial, focusing on more than 3,000 patients presenting with ACS and treated with PCI from September 2013 to February 2018. The primary endpoint was a composite of all-cause mortality, myocardial infarction and stroke after one full year. Its safety endpoint was Bleeding Academic Researching Consortium (BARC) type three to five bleeding.
“This analysis is, to our knowledge, the first study to directly compare outcomes between ticagrelor-based and prasugrel-based strategies in patients with ACS who are treated with PCI,” wrote lead author J. J. Coughlan, MB, BCh, a specialist at the Technical University of Munich in Germany, and colleagues. “The PCI procedure for these patients reflected contemporary practice with new-generation drug-eluting stents.”
While 1,676 patients with a mean age of 64.4 years old received ticagrelor, 1,701 patients with a mean age of 64.7 years old received prasugrel. Overall, the study’s primary endpoint occurred in 9.8% of patients from the ticagrelor group and 7.1% of the prasugrel group. Myocardial infarctions were observed in 5.3% of the ticagrelor group and 3.8% of the prasugrel group. The study’s safety endpoint occurred in 5.3% of patients from the ticagrelor group and 4.9% of the prasugrel group.
“Overall, these data support the preference for a prasugrel-based strategy vs a ticagrelor-based strategy in patients presenting with ACS who are treated with PCI,” the authors concluded. “Because these observations are based on a post-randomization subgroup, these findings should be regarded as hypothesis generating, and dedicated randomized clinical trials may be warranted to confirm these findings.”
Click here for the full analysis.
Results of Prior study are:
Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization
N Engl J Med 2012; 367:1297-1309 October 4, 2012DOI: 10.1056/NEJMoa1205512
-
BACKGROUND
The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated.
METHODS
In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel.
RESULTS
At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group.
CONCLUSIONS
Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number,NCT00699998.)
SOURCE
Inappropriate Prasugrel Use in One in Five PINNACLE Patients
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.
SOURCE
http://www.medscape.com/viewarticle/826397?nlid=58944_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
vaishnavee24
zraviv06
zs22
Leave a Reply