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Developed in Canada and conducted by researchers from the University of Ottawa Heart Institute, in partnership with Spartan Bioscience, the world’s first bedside genetic test has received acknowledgment by The Lancet, the world’s leading general medical journal.

The article Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial, reports on the use of a simple cheek swab test, the Spartan RX CYP2C19, performed by nurses at the patient’s bedside. This revolutionary technology allows doctors to rapidly identify patients with a genetic variant known as CYP2C19*2. Cardiac stent patients with this variant are at risk of reacting poorly to standard anti-platelet therapy with Plavix® (clopidogrel).

The study demonstrated that tailored drug treatment therapy made possible by the genetic testing successfully protected all of the patients with the at-risk genetic variant from subsequent adverse events, while 30 per cent of patients treated with standard therapy did not receive adequate protection.

“For the first time in medicine, nurses were able to perform DNA testing at the patient’s bedside. This is a significant step towards the vision of personalized medicine,” said Dr. Derek So, Interventional Cardiologist at the University of Ottawa Heart Institute (UOHI), and principal investigator of the RAPID GENE study.

Study Details

The RAPID GENE study enrolled 200 patients who were being treated with cardiac stenting for an acute coronary syndrome or stable angina. Patients were randomized to a treatment strategy of rapid point-of-care genotyping and Effient® (prasugrel) for CYP2C19*2 carriers, or to standard therapy with Plavix® (clopidogrel). The Spartan RX CYP2C19 bedside DNA test was performed by nurses who received a 30-minute training session, but had no prior laboratory training. The test had a sensitivity of 100% and a specificity of 99.4% compared with DNA sequencing. For CYP2C19*2 carriers, treatment with prasugrel completely eliminated High on-treatment Platelet Reactivity (HPR). HPR is a marker for patients at risk of complications after stenting. In contrast, 30.4% of carriers receiving clopidogrel had HPR at 1 week.

New research finds ongoing treatment with ticagrelor safe and effective in patients with acute coronary syndrome.

Ticagrelor, a potent anti-platelet medication, was approved by the Food and Drug Administration in the summer of 2011 and is known to significantly reduce the risk of stroke, heart attack, vascular death and death overall in patients with acute coronary syndromes (ACS), which are characterized by symptoms related to obstruction in coronary arteries, which supply blood to the heart.  Now, new research from Brigham and Women’s Hospital (BWH) shows that the use of ticagrelor not only reduces the time to a first cardiovascular event (the metric used in most trials) but also significantly reduces the time to a second cardiovascular event or death, and reduces total events including cardiovascular death, heart attack, stroke, ischemic events and urgent revascularization.  These findings will be presented at the American College of Cardiology Scientific Sessions on March 25, 2012.

“These data help show both clinicians and patients that if a patient is on ticagrelor and experiences a cardiac event, continued use of this anti-platelet is both safe and effective, and may prevent even more cardiac events than we previously thought” said Payal Kohli, MD a cardiology fellow and BWH researcher in the TIMI Study Group, who is the lead author on this study.

Researchers analyzed data from the PLATO study, where 18,624 patients with ACS were randomly allocated to receive aspirin plus either ticagrelor or clopidogrel. In this cohort of patients, 318 experienced multiple cardiac events during the follow up period. In addition to observing a reduction in the average number of events per patient, and a reduction in total vents, researchers also note that there was no difference in bleeding in patients taking ticagrelor compared to those taking clopidogrel, although the number of bleeding events may have been too small to detect a difference.

“Interestingly, we also found that that those patients who had more cardiac events tended to be older, have a lower body weight and have a higher number of cardiovascular risk factors.  There were also a higher proportion of females in this group.” Kohli said.

Urban legend warns shoveling snow causes heart attacks, and the legend seems all too accurate, especially for male wintery excavators with a family history of premature cardiovascular disease. However, until recently this warning was based on anecdotal reports.

Two of the most important cardiology associations in the US include snow -shoveling on their websites as a high risk physical activity, but all the citation references indicate that this warning was based one or two incidents.

“We thought that this evidence should not be enough to convince us that snow -shoveling is potentially dangerous, ” says Adrian Baranchuk, a professor in Queen’s School of Medicine and a cardiologist at Kingston General Hospital.

Dr. Baranchuk and his team retrospectively reviewed KGH patient records from the two previous winter seasons and discovered that of the 500 patients who came to the hospital with heart problems during this period, 7 per cent (35 patients) had started experiencing symptoms while shoveling snow.

“That is a huge number,” says Dr. Baranchuk. “7 per cent of anything in medicine is a significant proportion. Also, if we take into account that we may have missed some patients who did not mention that they were shoveling snow around the time that the episode occurred, that number could easily double.”

The team also identified three main factors that put individuals at a high risk when shoveling snow. The number one factor was gender (31 of the 35 patients were male), the second was a family history of premature coronary artery disease (20 of the 35 patients), and the third was smoking (16 out of 35 patients). The second two factors may carry much more weight than the first, however, since the team could not correct for high rate of snow shoveling among men in their sample.

A history of regularly taking four or more cardiac medications was found to be preventative.

Dr. Baranchuk collaborated on this study with Wilma Hopman (Department of Community Health and Epidemiology, KGH Clinical Research Centre), William McIntyre, (Queen’s medical resident), and Salina Chan and David Schogstad-Stubbs (Queen’s medical students).

These findings were recently published in Clinical Research in Cardiology.

From Eurekalert November 23 2011

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

(Media-Newswire.com) – HOUSTON — ( April 5, 2011 ) — New guidelines for the management of patients with unstable angina and non-ST-elevation myocardial infarction ( termed acute coronary syndromes ) have been released by the American College of Cardiology and the American Heart Association. The guidelines were created by a consortium of national experts including a cardiologist from Baylor College of Medicine.

“This important document is an update of the 2007 ACC/AHA guidelines. We examined past recommendations, reviewed the clinical data that accrued since then, and created the most updated set of recommendations that can provide guidance for physician in their patient care,” said Dr. Hani Jneid, assistant professor of medicine and interventional cardiologist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center. Dr. Jneid was part of the 15-member writing group, led by Dr. R. Scott Wright, professor of medicine at the Mayo Clinic.

Leading cause of death
Unstable angina occurs when the heart doesn’t get enough blood flow and oxygen, as a result of blockage in one or more of the coronary arteries. This results in chest discomfort, and when prolonged beyond a 20-30 minute period, may progress into myocardial infarction ( or a heart attack ) with death of heart muscle cells. Those guidelines therefore address one of the most commonly encountered clinical conditions and a leading cause of death and morbidity in the United States and the Western World.

Jneid indicated that the guidelines have been updated with a plethora of new recommendations. These include, but are not limited to, recommendations pertinent to early hospital care, such as the timing of cardiac catheterization after an acute coronary syndrome, the use of intravenous anti-platelet and anticoagulant medications, and especially the clinical application of prasugrel, a novel oral anti-platelet drug. New recommendations pertinent to patients with diabetes and chronic kidney disease, as well as recommendations for quality of care and outcome monitoring after an acute coronary syndrome have also been proposed.

Clinically relevant changes
“Our multifaceted group worked tirelessly to review the literature and dissect clinical studies and experimental evidence to come up with the meticulous and clinically relevant changes,” Jneid said. “This process of periodically updating Guidelines is very important to patient care, especially in the dynamic and rapidly evolving field of cardiovascular medicine. The careful revisions and scrutiny of the document and the choice of unbiased and balanced team of experts are all a testimony of the high standards set by the ACC and AHA in constructing these guidelines, as supported by report of the Institutes of Medicine last month.”

In addition to Drs. Scott and Jneid, the national expert panel is made up of Drs. Jeffrey Anderson, Cynthia Adams, Charles Bridges, A. Michael Lincoff, Donald Casey, Eric Peterson, Steven Ettinger, George Philippides, Francis M Fesmire, Pierre Theroux, Theodore Ganiats, Nanette Wenger and James Zidar. Of note, this guidelines update was created in collaboration with prominent medical organizations, including the American Academy of Family Physicians, the American College of Emergency Physicians, the Society for Cardiac Angiography and Interventions, and the Society of Thoracic Surgeons.

The 2011 focused update will be published in the Journal of the American College of Cardiology and Circulation: Journal of the American Heart Association. It has been released online ahead of print on the ACC and AHA web sites.