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SAN FRANCISCO, CA – WEDNESDAY, NOVEMBER 9, 2011 – Non-adherence to antiplatelet therapy – which prevents blood clots following percutaneous coronary intervention (PCI) – was associated with higher rates of both ischemic and bleeding events at 30 days. Results of the PARIS registry were presented today at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation.

Dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine is the cornerstone of treatment for patients presenting with acute coronary syndromes and for patients undergoing percutaneous coronary intervention (PCI) with stents. Current guidelines recommend at least one year of DAPT for all patients following PCI with a drug-eluting stent (DES), and 30 days after a bare metal stent.

Premature discontinuation of DAPT (within the first six months after implantation of DES) has been associated with an increased risk of stent thrombosis, but the optimal duration of DAPT has not yet been precisely determined, especially with regard to second generation stents.

The PARIS Registry (Patterns of Non-Adherence to Anti-Platelet Regimens In Stented Patients: An Observational Single Arm Study) is a multicenter, multinational, observational study with an “all comers” design. The study will follow 5,033 subjects for approximately 24 months post stent implantation (bare metal and drug-eluting stents.)

The objectives of this study are to examine modes of non-adherence to DAPT in patients following stenting, and to evaluate subsequent clinical outcomes and their relation to non-adherence.

The incidence of non-adherence to DAPT in this “real world” international observational registry was 2.0% at 30-day follow-up.

In the non-adherent population at 30-days:

• 69% had disruption of therapy – mostly due to non-compliance (61%) and bleeding event (32%)
• 19% had interruption of DAPT – mostly due to surgery or medical procedures (67%)
• 12% had discontinuation of therapy (recommended by physician)

“Importantly, any non-adherence (aspirin or thienopyridine – non-adherence was equally distributed) was associated with higher rates of both ischemic and bleeding events at 30 days including death, myocardial infarction, definite and/or probable stent thrombosis, target vessel revascularization, and bleeding (BARC≥3),” said Roxana Mehran, MD, the co-principal investigator of the study. Dr. Mehran is Professor of Medicine at Mount Sinai School of Medicine and Director of Interventional Cardiovascular Research and Clinical Trials at the Zena and Michael A. Wiener Cardiovascular Institute. She also serves as Chief Scientific Officer of the CRF Clinical Trials Center.

“There was a six-fold increase in odds for definite or probable stent thrombosis associated with non-adherence compared to adherence to DAPT at 30 days. The two year data will be more definitive and should be able to link the patterns of non-adherence with important clinical events,” Dr. Mehran said.

The PARIS trial is sponsored by Mount Sinai School of Medicine with grant support from Sanofi-Aventis and Bristol-Myers Squibb. Dr. Mehran reported no other financial support from the companies except for the research grant.

Source: Eurekalert

SAN FRANCISCO, CA – NOVEMBER 9, 2011 – A clinical trial of patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and stable angina showed that a strategy of rapid genotyping followed by selective administration of prasugrel to carriers of a common genetic variant (CYP2C19*2) resulted in a decreased rate of high on-treatment platelet reactivity (platelet non-responder rate) compared to standard therapy.

The investigation also demonstrated that point-of-care genetic testing is clinically feasible and is capable of facilitating rapid personalization of antiplatelet therapy. Results from the RAPID GENE trial were presented today at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation.

The RAPID GENE (Reassessment of Anti-Platelet Therapy Using An Individualized Strategy Based on Genetic Evaluation) study utilized a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and evaluated a pharmacogenetic approach to dual antiplatelet therapy following PCI.

The CYP2C19*2 allele, a common genetic variant found in up to 25% of Caucasians and 40% of Asians, is associated with increased rates of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in individuals receiving clopidogrel. In March 2010, the US FDA issued a boxed warning indicating that patients carrying these genetic variants may not receive adequate protection from clopidogrel.

The RAPID GENE investigators hypothesized that a strategy of rapid genotyping followed by selective administration of prasugrel to CYP2C19*2 carriers would decrease the rate of high on-treatment platelet reactivity (platelet non-responders) compared to standard therapy. The primary objective of the study was to evaluate the first point-of-care genetic test in medicine for its accuracy and potential clinical utility.

Existing genetic testing methods are time-consuming, require laboratory expertise and cannot be performed at the clinical bedside. These limitations preclude timely identification of the CYP2C19*2 allele in patients undergoing PCI.

In the RAPID GENE study, which was conducted by a team of investigators at the University of Ottawa Heart Institute, 200 patients undergoing PCI for ACS or stable angina were randomized to a strategy of rapid point-of-care genotyping with selective administration of 10 mg of prasugrel to CYP2C19*2 carriers or to standard therapy with 75 mg of clopidogrel daily.

The study utilized the first point-of-care genetic test in medicine, which overcame many of the previous obstacles that had prevented routine clinical genetic testing. The test featured: • A saliva (buccal) swab performed by clinical nurses with no prior training in genetic laboratory techniques • A one step insertion of the swab into testing machine • Sixty minutes to identify whether individuals carried the at-risk genetic variant.

The primary endpoint was the proportion of CYP2C19*2 carriers with impaired anti-platelet therapy response (high on-treatment platelet reactivity) in the rapid genotyping arm compared to those in the standard therapy arm after seven days. Secondary endpoints included sensitivity and specificity of the point-of-care test compared to conventional genetic testing, other measures of platelet function among CYP2C19*2 carriers and the whole cohort by randomization, MACE, and bleeding risk measured by the TIMI scale.

Enrollment of the study was completed in July 2011. In total, 187 patients completed follow-up with 91 patients in the rapid genotyping group and 96 patients in the standard therapy group.

The primary endpoint showed that the proportion of CYP219*2 carriers with high on-treatment platelet reactivity (PRU> 234) was 0% in the rapid genotyping group compared with 30.4% in the standard therapy group.

Secondary clinical outcomes showed there were no major adverse cardiovascular events in either group at seven and 30 days. There was no significant difference in TIMI major bleeding between the groups with 2.2% in the rapid genotyping group versus 1.0% in the standard therapy group.

The RAPID GENE trial demonstrated that point-of-care genetic testing following PCI performed at the bedside by clinical nurses permits accurate identification of CYP2C19*2 carriers. It further showed that point-of-care genetic testing is clinically feasible and facilitates rapid personalization of antiplatelet therapy.

“RAPID GENE is the first study to report the use of a point-of-care genetic test in medicine,” said lead researcher, Derek So, MD. Dr. So is a Staff Cardiologist at the University of Ottawa Heart Institute and an Assistant Professor in the Department of Medicine at the University of Ottawa.

“These results will be integral for the application of future pharmacogenetic strategies in antiplatelet therapy in the context of percutaneous coronary intervention for acute coronary syndrome and stable angina. This represents the validation of the first point-of-care genetic test in clinical medicine. This proof-of-concept study will be applicable to all areas of medicine and will lead to larger scale trials evaluating the role pharmacogenomic treatment strategies,” Dr. So said.

The RAPID GENE trial is funded by Spartan Biosciences Inc. Dr. So reported no financial relationship with the company.

Source: Eurekalert

SAN FRANCISCO, CA – NOVEMBER 9, 2011 – A clinical trial comparing prasugrel to clopidogrel for patients with high on-clopidogrel platelet reactivity (HCPR) following percutaneous coronary intervention (PCI) was ended early due to relatively few occurrences of cardiac death or myocardial infarction – the primary endpoint – at six month follow up.

Results of the TRIGGER-PCI (Testing platelet Reactivity In patients underGoing elective stent placement on clopidogrel to Guide alternative thErapy with pRasugrel) trial were presented today at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation.

The risk of ischemic events after percutaneous coronary intervention (PCI) is elevated in patients with high on-clopidogrel platelet reactivity (HCPR). Novel P2Y12-receptor antagonists, such as prasugrel, are more potent than clopidogrel and may, thus, improve outcome with respect to ischemic events, but may also increase bleeding risk.

The trial was a multi-center, double-blind, randomized controlled trial. Platelet reactivity was assessed two to seven hours after the first maintenance dose of clopidogrel 75 mg on the day after PCI following loading with clopidogrel 600 mg and randomized to either prasugrel or clopidogrel. TRIGGER-PCI aimed to randomize 2,150 patients to have a 93% power for detecting a 50% relative risk reduction on prasugrel in the primary study endpoint (cardiovascular death or myocardial infarction within six months).

The study was terminated prematurely for futility at March 18, 2011 at which 236 patients completed the six-month follow up. Only one clinical endpoint, a peri-procedural myocardial infarction, was observed.

“High on-clopidogrel platelet reactivity (>208 PRU by VerifyNow P2Y12 test) was observed less frequently than expected,” said Dietmar Trenk PhD. Dr. Trenk is Professor and Head of Clinical Pharmacology at Herz-Zentrum Bad Krozingen in Germany.

Dr. Trenk noted that the trial demonstrated that compared with standard-dose clopidogrel 75 mg, prasugrel 10 mg substantially decreased platelet reactivity in patients with high on-clopidogrel platelet reactivity after elective PCI.

“Given the low event rate in elective PCI patients without peri-procedural complications, it was not possible to assess the risk/benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility,” Dr. Trenk said.

The trial is sponsored by Eli Lilly and Company and Daiichi Sankyo Co., Ltd. Dr. Trenk reported consulting fees/honoraria and speaker honoraria from both companies, AstraZeneca and Sanofi-Aventis.

Source: Eurekalert

Platelet Function Testing May Be Used to Aid Patient Management

SAN DIEGO, March 31, 2011 /PRNewswire/ — Accumetrics, Inc., developer of the VerifyNow® System, the first rapid and easy-to-use point-of-care system for measuring platelet reactivity to multiple antiplatelet agents, announced today that a new recommendation for platelet reactivity testing has been incorporated into the updated 2011 ACCF/AHA Guidelines for the Management of UA/NSTEMI Patients.

The Guidelines, published online in the Journal of the American College of Cardiology(1), signify the growing focus and importance of platelet reactivity testing in a variety of patient populations, including UA/NSTEMI and ACS/PCI. The IIb (B) recommendation suggests that an approach of assessing platelet reactivity in combination with other procedural and patient characteristics may be considered to aid in patient management decisions.

“The addition of platelet reactivity testing to the Guidelines captures what we have already implemented at Scripps,” said Matthew J. Price, MD, of the Scripps Translational Science Institute and Scripps Clinic in La Jolla, CA. “We believe that when considering alternative approaches for the management of patients that require antiplatelet therapy, an individualized approach that incorporates platelet reactivity testing is warranted in an attempt to minimize further ischemic events.”

The Update also provides guidance on the rapidly expanding treatment options for patients requiring antiplatelet medications. “With the availability of newer antiplatelet agents, it has become challenging for a physician to determine how to manage individual patients,” stated Kevin Croce, MD, PhD, Interventional Cardiologist at Brigham and Women’s Hospital. “By utilizing platelet reactivity testing as recommended in this new Guideline, we feel we have a clearer picture on how to optimally manage our patients at the Brigham in this increasingly complex clinical setting.”

The release of these Guidelines further elevates awareness of platelet reactivity testing as an important topic, and sets the stage for additional data and discussions at the 2011 ACC Scientific Sessions. New data from a patient-level meta-analysis will be presented by Dr. Somjot Brar on April 3rd, and Dr. Paul Gurbel and Dr. Matthew Price will discuss “The Application of Available Data in Clinical Practice” during the Accumetrics Industry Expert Theater Program on April 4th.

“The ACCF/AHA UA/NSTEMI Guidelines follow the STS/SCA Blood Conservation Guidelines released earlier this month, reinforcing the clinical importance of point-of-care platelet reactivity testing,” said Timothy I. Still, President and CEO of Accumetrics. “With the VerifyNow System, Accumetrics is proud to be the leader in providing this critically important information to aid in the management of patients.”

The VerifyNow System is widely used in various clinical settings where antiplatelet medications are prescribed to reduce the occurrence of future thrombotic events such as heart attack and stroke.

About Accumetrics

Accumetrics is committed to advancing medical understanding of platelet function and enhancing quality of care for patients receiving antiplatelet therapies by providing industry-leading and widely accessible diagnostic tests for rapid platelet function assessment.

Accumetrics’ VerifyNow System is the first rapid and easy-to-use platform to help physicians determine an individual’s response to multiple antiplatelet agents. Addressing every major antiplatelet drug, including FDA-cleared products for aspirin, P2Y12 inhibitors (e.g. prasugrel (Effient®) and clopidogrel (Plavix®)), and GP IIb/IIIa inhibitors (e.g. ReoPro® and Integrilin®), the VerifyNow System provides valuable information to help physicians make informed treatment decisions. For more information about the Company and its products, visit www.accumetrics.com.

The Accumetrics logo and VerifyNow are registered trademarks of Accumetrics, Inc. ReoPro is a registered trademark of Centocor, Inc. Integrilin is a registered trademark of Millennium Pharmaceuticals. Plavix is a registered trademark of sanofi-aventis. Effient is a registered trademark of Eli Lilly and Company.

(1) Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. Published online Mar 28, 2011; doi:10.1016/j.jacc.2011.02.009.