By Turna Ray
Medco Health Solutions said last week that preliminary data from a study conducted in collaboration with Quest Diagnostics indicates that patients taking statins are more likely to take their medications if they have been genetically tested for the KIF6 marker.
According to Medco, the Additional KIF6 Risk Offers Better Adherence to Statins, or AKROBATS, trial is the first "real-world" study to prospectively evaluate the impact of KIF6 gene testing on patient adherence to cholesterol-lowering drugs. Quest subsidiary Celera markets the KIF6 Genotyping Assay, which tests for variants in the KIF6 gene that have been associated with response to some statins.
The full results of the AKROBATS trail will be reported next spring.
Independent of the influence of genetics, taking statins as prescribed has been shown to improve patient outcomes and reduce adverse events that may occur as a result of not following doctors' orders. A Medco study published in the American Journal of Cardiology in June reported that patients who took statins as prescribed more than 90 percent of the time reduced total healthcare costs by $944 per patient over 18 months and significantly lowered their risk of hospitalization due to heart complications.
However, Medco and Celera note in their description of the AKROBATS trial that the discontinuation of statins is "quite substantial," with two-year adherence rates ranging from 25 percent to 40 percent. Since KIF6 carriers receiving statins have been shown in some studies to have a greater cardiovascular risk reduction compared to non-carriers using statins, the AKROBATS investigators set out to determine whether knowledge of KIF6 status would encourage patients to remain on their medication.
While the trial is not intended to demonstrate the effectiveness of KIF6 as a marker for cardiovascular risk or as a PGx marker for statins, it is taking place amid several unresolved questions for the test.
Celera filed a premarket approval application for the KIF6 test with the US Food and Drug Administration earlier this year, submitting data from several large retrospective studies. However, the agency sent the firm a notice in April asking it to conduct a prospective, randomized trial showing that the test can identify which patients at risk for coronary heart disease would benefit from taking statins (PGx Reporter 4/27/2011).
Celera claims that it has validated KIF6 in 55,000 people across nine studies showing the link between the KIF6 Trp719Arg allele and coronary heart disease risk, and the association between KIF6 and statin benefit. The data, according to Celera, suggest that KIF6 carriers have between 22 percent and 55 percent greater risk for cardiac events than non-carriers, and that people with this genetic polymorphism also benefit more from statin therapy than those who are KIF6 non-carriers.
Counter to this, a body of evidence has been emerging that sheds doubt on whether KIF6 should be used to determine which patients are at risk of cardiac events and should be treated with statins. A large meta-analysis, led by Themistocles Assimes of Stanford University and published in the Journal of the American College of Cardiology last year, found that more than 17,000 patients and 39,000 controls in 19 studies failed to demonstrate that carriers of the KIF6 Trp719Arg allele had an increased risk of coronary artery disease compared with non-carriers. Furthermore, this same analysis also suggested that the KIF6 marker may not be predictive of statin benefit in patients (PGx Reporter 10/13/2010).
Medco stressed that AKROBATS is not trying to prove the predictive or the prognostic value of KIF6 testing, but is gauging whether genetic testing inspires people to stick more closely to their prescriptions.
"AKROBATS addresses a completely different question," the Medco spokesperson said, noting that the aim of the trial is to show the value of a personalized medicine intervention in improving outcomes and lowering costs. Furthermore, the "relationship between statin adherence and cardiovascular risk reduction and healthcare costs is well established," the spokesperson added.
However, some have questioned whether Medco should be studying the impact of a personalized medicine strategy using a gene marker with unproven clinical value. Following the publication of the KIF6 meta-analysis in the JACC, Assimes told PGx Reporter that he thought the Medco statin adherence study "should be stopped given the new evidence provided by our study, as well as … [by other] studies."
In conducting the AKROBATS study, "the information communicated to the patient was based on contemporary published scientific information, and all was extensively reviewed internally and approved for study subject use by the institutional review board," a Medco spokesperson said. The specific information communicated to the patient about the clinical utility of KIF6 testing, which may have influenced his or her decision to stick to their statin prescription, will be revealed when full results of the study are published.
Medco conducted AKROBATS after assessing the current body of evidence on the association between the KIF6 variant and cardiac outcomes and concluded that "the plurality of these [data] indicate a greater risk reduction with statin therapy among patients who are KIF6 variant carriers compared to non-carriers," the Medco spokesperson said. Furthermore, all clinical evaluations of the variant have been retrospective studies, Medco noted.
"In contrast, the AKROBATS trial is the first prospective evaluation of the potential clinical utility of KIF6 testing … on patient adherence to statin therapy, and the top-line results clearly confirm that it does have clinical utility, measured by statin adherence, when testing is applied in a real-world practice setting," the spokesperson said.
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