As reported in The Pipeline, researchers from the Medco Research Institute in conjunction with the Mayo Clinic reported findings today from the first national, prospective comparative effectiveness study that used genetic testing to determine warfarin dose levels. One of the most common anticoagulants used in high-risk patients, warfarin exhibits a large inter-individual dosing requirement because of the wide variety of sensitivities to the drug. Decisions about dosing requirements can have a serious clinical impact--patients with high-sensitivity to Warfarin are at a high risk of bleeding while patients with a low-sensitivity are at risk of thromboembolism. Genetic testing provides a potential proactive solution to determine appropriate dose.
Using a known genetic expression of Warfarin sensitivity, the Medco-Mayo Warfarin Effectiveness Study (MM-WES) recruited patients across the country that were about to start on the drug. Patients underwent testing and were classified according to their sensitivity to warfarin based on their genotype. Based on this genetic expression, physicians were advised to adjust the dose levels of their patients. After six months, the trial results showed a substantial reduction in all-cause hospitalization (31 percent) and in hospitalization for bleeding or thromboembolism (29 percent) for those patients that had undergone genetic testing.
While the findings are indeed impressive, Dr. Mandeep Mehra, who commented on the study expressed concern that the trial design had some troublesome flaws. His largest concern stemmed from a perceived Hawthorne effect, in which subjects improve behavior as a reaction to being studied. In this case, the physicians of the patients being studied were believed to have provided additional care and oversight to their patients simply because they were under investigation. Dr. Mehra believed that this extra layer of protection, realized through a more aggressive management of warfarin therapy may have made the impact less emblematic of true 'real world' warfarin patients. If this is the case, the improved results seen in the study may be less about the response to the genotypic expression and more about an uncommon increase in vigilance among the physicians caring for these patients.
A striking aspect of the study was the physician interest in participation. Physicians had a 75 percent response rate when contacted by the trial investigators. Despite a lack of familiarity with the genetic test for warfarin, physicians were willing to send genetic samples for analysis and to respond to recommendations based on the genotypic expression. This may be evidential of the dawning age of personalized medicine, though operational imepediments still exist. The cost of the test, at $200-$400, can quickly add up considering the volume of patients being treated with Warfarin--approximately 2 million individuals start on the drug each year. However, with expanded availability and lower cost, widespread use of genetic testing prior to the start of drug therapy may grow quickly.
At the ACC Scientific Sessions yesterday, the results of the Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP-AF) trial were presented by Dr. Douglas Packer and colleagues from the Mayo Clinic. According to researchers, the cryoablation technology--Medtronic's Arctic Front CryoAblation Catheter System--uses extreme cold to cryoablate the tissue of the pulmonary vein, requiring only one or two "freezes" rather than having to move the catheter to multiple locations, as is traditionally done in RF ablation after pulmonary vein isolation.
In the STOP-AF trial, 245 patients with paroxysmal AF were enrolled at 26 centers; patients were randomized in a 2:1 manner to either PVI with the cryoballoon, or treatment with antiarrhythmic drug therapy. Results from the trial demonstrated that after one year, 70% of patients treated with the cryoablation technology were free from AF, as compared with 7% of patients treated with antiarrhythmic drug therapy.
According to Dr. Parker, the cryoablation is a "relatively new technology in the hands of the investigators using them." And, though the average procedure time is six hours and the procedure has a fairly steep learning curve, Dr. Parker anticipates a reduction in length with additional experience. As for the continuation of warfarin in patients having undergone the procedure, researchers believe it is largely dependent on their risk of thromboembolic events. (theheart.org, 3/15; Cardiosource, 3/15).
Results from a proof of concept study suggest that a non-invasive fingertip stress test can identify patients who have significant coronary artery disease (CAD), defined as coronary lesions with diameter stenosis of greater than 50 percent and requiring revascularization. The test has been developed by an Israeli company called Spirocor and measures the blood flow in the finger in response to paced breathing for 70 seconds. Researchers believe the test works by measuring modifications in fluctuations in the peripheral pulse which occurs when patients have significant CAD.
The proof of concept study involved 97 patients who were referred for cardiac catheterization to exclude significant CAD. All patients were tested prior to cardiac catheterization and patients undergoing revascularization were also tested after the procedure. The results showed that the test successfully identified patients with significant CAD and also tracked marked improvements once patients that had undergone revascularization.
Given these positive results, a phase 3 pivotal trial of the test, called SPIROCOR Coronary Outcome by Respiratory Stress Examination (Score) is being conducted in the US. The trial plans to enroll 1,000 patients and will be compared against an ECG stress test. For more information, please see www.spirocor.com and the following www.theheart.org.
Results from a recent pilot study, the Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients (HOMEOSTASIS), published in the February 22nd online edition of Circulation, demonstrated the potential of a left atrial (LA) pressure sensor--St. Jude Medical's HeartPOD--to guide daily diuretic dosage adjustments in heart failure patients.
According to Dr. William Abraham, the senior author of the study, patients receive a "tailored algorithm" from their physician that adjusts diuretic dosage based on LA pressure. The HeartPOD generates such pressure readings in a handheld "patient advisor module" using a lead that advances transvenously from the right atrium and whose sensor tip is anchored in the left atrium.
Results from the pilot study--which followed 40 patients, NYHA Class III or ambulatory in Class IV for an average of 25 months--consisted of guideline-based treatment for the first three months, followed by optimized treatment based on LA pressure data using a personalized dosing plan to achieve optimal pressure. At one year, survival free of decompensation was 72%, with 69% at two years and 61% at three years. The ultimate goal of this device--which improved LV function and improved survival free of acute decompensation without affecting renal function--is to optimize patients' therapy outside the hospital by keeping LA pressure within the preferred range, thereby avoiding decompensation. Using LA pressure information, non-diuretic medications too can be optimized.
Please follow this link to access the study [subscription required] (Ritzema J, et al. Physician-directed patient self-management of left atrial pressure in advanced chronic heart failure. Circulation 2010; 121:1086-1095).