CV Events, Bleeding Drop When Antiplatelet Drugs Are Picked With Genetic Tests, PHARMCLO Finds

Patients with acute coronary syndrome (ACS) who used a genetic test to select an antiplatelet drug were 42% less likely to have a cardiovascular (CV) event or major bleeding, according to a study presented Sunday at the 67th Scientific Session of the American College of Cardiology, taking place in Orlando, Florida.

ACS, which includes heart attacks and chest pains known as unstable angina, puts a patient at future risk of ischemic events, including a stroke. This is caused when a clot blocks a blood vessel; to prevent this, patients take aspirin and an antiplatelet therapy, a P2Y12 receptor antagonist. The study, PHARMCLO, is the first to combine clinical data with genetic information, giving patients a personalized approach to the selection of 1 of 3 therapies: clopidogrel, ticagrelor, or prasugrel. Ticagrelor (Brilinta) is available only as a branded product.

With the genetic test, patients were less likely to experience a heart attack, stroke, or death from CV causes or major bleeding, which was the study’s primary endpoint, compared with patients who did not use a test.

“Selecting treatment on the basis of genetic data in addition to considerations concerning the patients’ clinical characteristics may lead to a more personalized, and therefore more efficient, antiplatelet therapy, thus reducing both ischemic and bleeding risk,” Diego Ardissino, MD, cardiologist at Azienda Ospedaliero-Universitaria di Parma, Italy, and the study’s lead author, said in a statement. “PHARMCLO is the first step of a new approach that will see a shift in emphasis away from trying to discover ever more potent antithrombotic drugs and toward ensuring that the right therapy is given to each individual patient.”

Researchers in Italy randomized 888 patients who were hospitalized for ACS; half received standard care, in which doctors prescribed 1 of the 3 P2Y12 receptor antagonists based on the patient’s clinical characteristics. The other half received a genetic test, which doctors evaluated alongside clinical data. After a year, the composite primary endpoint had been reached in 25.9% of patients in standard care and only 15.8% of those who took the genetic test.

Testing caused more frequent prescribing of ticagrelor, a more powerful drug that does not have a generic, and less frequent prescribing of clopidogrel (Plavix), which is available as a generic.

Researchers developed a specialized genetic screening tool for the study. Lack of certification for the screening tool caused Italian regulators to halt recruitment of additional patients, but the original patients are being followed.

The study was published online in the Journal of the American College of Cardiology.

Patients Given Drug Vouchers, but Many Don’t Use Them

A study being presented Sunday at the 67th Scientific Session of the American College of Cardiology showed that giving patients vouchers for antiplatelet therapy produced a modest improvement on adherence, but the study’s bigger lesson was that even when patients have drug vouchers, some patients don’t take the drugs.

The vexing problem of adherence—long seen as a major challenge in healthcare—showed up in ARTEMIS, a study that compared 2 groups of patients who had just had heart attacks. One group was given usual care, and the other was given a voucher to cover the co-payment for anti-platelet therapy. The study found the vouchers brought a modest improvement in adherence—randomly selected blood draws showed 8.23% of the intervention group was not adherent, compared with 12.35% of the usual care group. But the study also showed that 28% of the intervention group never used their vouchers, and this group had some of the worse adherence rates and highest rates of major adverse cardiac events.

Adherence is such a problem that most healthcare economists consider 80% adherence an acceptable figure. Like others, this study led by Tracy Wang, MD, MHS, MSc, associate professor of Medicine at Duke University School of Medicine, used records of pharmacy refills as one measure of adherence. But Wang and fellow researchers were puzzled why adherence rates in the random blood draws of 966 patient did not align with the pharmacy records of 8360 patients, or patients’ personal estimates of their adherence. Pharmacy records suggested adherence among the intervention group was only 44.8%, and 53% in the usual care group.

“The study met its primary endpoint of improving adherence to guideline-recommended therapy at one year,” Wang, said in a statement. “When affordability was not an issue, physicians felt less restrained in their ability to choose medications, and patients were 16% less likely to prematurely stop taking the medication.”

ARTEMIS enrolled 11,001 patients treated for a heart attack 301 US hospitals. All patients had health insurance; 64% had commercial coverage, 42% had Medicare, and 9% had Medicaid. Of the study participants, 17% said they had not filled a prescription due to cost. Of the 3 P2Y12 receptor antagonists, clopidogrel (Plavix), is available in generic form, and the more powerful ticagrelor ticagrelor (Brilinta) is available only as a branded product Prasugrel was prescribed less frequently in the study.

“While we know that patients often overestimate their own adherence, I was surprised by the size of the discrepancy between patient reports and pharmacy fill records,” Wang said. “I suspect the ‘true’ answer is somewhere in between patient reports and pharmacy records, but both indicate that ensuring treatment adherence is still a huge problem.”

In her presentation, Wang said that when cost was removed as a consideration, physicians felt free to prescribe the therapy most appropriate with the guidelines. Yet there was no difference in outcomes between the group that received vouchers and the usual care group.

The study may have ended up with insufficient statistical power to identify a between-group difference for the co-primary endpoint, she said.

AstraZeneca funded the study.