An update of the GEMINI-ACS-1 trial found that switching of P2Y12 inhibitors based on the results of pharmacogenomics testing and reporting for reduced or enhanced function alleles of CYP2C19 was not common. Clopidogrel carries a black-box warning recommending testing because patients with the reduced function alleles have higher platelet reactivity and a potentially higher risk of ischemic events, especially following PCI.
Results of the update to the P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes trial were presented Tuesday by E. Magnus Ohman, MD, professor of medicine and member of the Duke Clinical Research Institute in Durham, North Carolina.
“GEMINI looked at clinical outcomes for rivaroxaban versus aspirin with either clopidogrel and ticagrelor,” Ohman said. “The choice of therapy was at the discretion of the clinician. This update looks at switching between these two agents.”
In the trial, reporting of the CYP2C19 status was mandatory.
A central lab reported CYP2C19 metabolizer status for 99.9 percent of the 3,037 patients. A total of 34.4 percent were ultra-metabolizers (UM), 37.8 percent extensive metabolizers (EM), 24.5 percent intermediate metabolizers (IM) and 3.2 percent reduced metabolizers (RM). The trial protocol made no recommendations regarding P2Y12 inhibitors or switching agents based on CP2C19 status.
A total of 6.5 percent of patients switched agents, with 8.5 percent of the ticagrelor group switching to clopidogrel and 4 percent of clopidogrel patients switching to ticagrelor.
CP2C19 status played a small role in switch decisions, Ohman said. The vast majority of patients did not switch, irrespective of their metabolizer status. And while patients with RM status were five times more likely to switch compared to UM patients, only 43 percent of RM patients switched from clopidogrel to ticagrelor because of metabolizer status. The other 57 percent switched due to nonbleeding adverse events, recurrent ischemic events, or another reason.
Only one patient switched from ticagrelor to clopidogrel because of metabolizer status. Other switches were due to nonbleeding adverse events, recurrent ischemic events or other reasons.
“Our findings do not support the utility of mandatory pharmacogenomics testing for P2Y12 inhibitor use because clinicians do not act on it,” Ohman said. “And we saw no increased risk of ischemic events or increased bleeding with the RM phenotype, suggesting the information is of little clinical value.”
Rivaroxaban 2.5 mg bid plus aspirin has the potential to reduce direct care costs an average of $682 for every patient treated. The estimate comes from a trial update of COMPASS, which compared cardiovascular outcomes for patients treated with rivaroxaban plus aspirin versus aspirin alone.
The primary trial found a 24 percent reduction in the risk for cardiovascular death, stroke or MI, said Andre Lamy, MD, associate professor of surgery at McMaster University in Hamilton, Ontario. The trial update examined the potential cost impact in the United States, Canada, France and Germany based on direct medical and procedural costs for all cardiovascular events in the trial.
U.S. treatment costs ranged from $6,871 for severe limb ischemia to $48,859 for stroke. Costs in the other four countries were lower, particularly for procedures, Lamy said.
“We are looking only at direct-care costs for cardiovascular events and procedures,” he said. “And the 2.5 mg dose of rivaroxaban has not been approved anywhere, nor do we know the list price. But we saw that rivaroxaban decreases the direct costs of hospitalization, procedures and other treatments for major cardiovascular events.”
Clinicians should not expect any significant subgroup differences when using dabigatran dual-therapy for patients undergoing PCI. The results of a subgroup analysis of the RE-DUAL PCI trial found no differences between the primary outcome and subgroups with acute coronary syndrome as the index event, drug-eluting versus bare metal stents or ticagrelor versus clopidogrel.
The primary trial compared two dabigatran doses, 150 mg and 110 mg, plus a P2Y12 inhibitor versus warfarin triple-therapy with a P2y12 inhibitor plus aspirin. Both doses of dabigatran showed non-inferior outcomes vs. warfarin therapy. And while the trial was not powered to show superiority with 2,725 patients, both dabigatran doses showed better efficacy.
“There were no interactions in the subgroups based on ACS, the type of stent used or the antiplatelet agent,” said Jonas Oldgren, MD, professor of medicine at Uppsala University in Sweden. “The benefits of dabigatran dual therapy were entirely consistent with the main results.”
Patients with previous PCI who are taking aspirin probably do not need to interrupt aspirin for noncardiac surgery. For every 1,000 patients with prior PCI, perioperative aspirin will prevent 59 MIs and cause eight major bleeds, according to findings from a post-hoc analysis of a subgroup of the 10,010 patients in the POISE-2 study comparing aspirin to placebo in patients undergoing noncardiac surgery.
“This was not a prespecified analysis because the steering committee did not expect to randomize patients with prior PCI,” said Michelle M. Graham, MD, professor of cardiology at the University of Alberta and the Mazankowski Alberta Heart Institute in Edmonton. “But 470 patients with prior PCI were randomized, which give us the opportunity to look at any potential subgroup effect.”
The subgroup analysis found that in patients with prior PCI, those taking aspirin had a 50 percent risk reduction for death or MI compared to placebo.
“Among those with prior PCI undergoing noncardiac surgery, perioperative aspirin may be more likely to benefit patients than to harm them,” Graham said.
Patients who take prasugrel or ticagrelor following MI and then switch to clopidogrel are not at increased risk for ischemic events, according to findings from PRAGUE-18, an academic study that examined one-year outcomes comparing patients who did and did not switch to clopidogrel. Because there was no industry support, patients had to pay for antiplatelet agents after discharge.
“Patients commonly switch to clopidogrel after discharge for economic reasons,” said co-principal investigator Zuzana Motovska, PhD, professor and head of acute cardiology at Charles University Third Medical Faculty in Prague.
“Most patients who switched because of cost did so immediately after discharge. Whether they switched or not, we saw no difference in the key endpoint of cardiovascular death or nonfatal stroke or MI,” Motovska said.