September 26, 2013 — Lead study investigators from Icahn School of Medicine at Mount Sinai presented their Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients (PARIS) study findings at the ESC Congress 2013 in Amsterdam organized by the European Society of Cardiology. Their new study results show among patients undergoing percutaneous coronary intervention (PCI) with stents, the risk of cardiovascular complications after stopping dual antiplatelet therapy (DAPT) is highly variable depending on the context, and some patients experience no complications at all.
“Our findings challenge existing paradigms for prolonging antiplatelet therapy in otherwise stable patients after PCI, and show that in a real-world setting physicians are making appropriate decisions in selecting low-risk patients for discontinuation,” said lead investigator Roxana Mehran, M.D., professor of Medicine in Cardiology and director of Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai.
“Conversely, when patients simply don’t comply or are forced off antiplatelet therapy because they are bleeding, their risk is significantly elevated,” she adds.
The PARIS study, a prospective, international, multicenter, observational registry trial led by Icahn School of Medicine at Mount Sinai, enrolled more than 5,000 patients with coronary artery disease undergoing PCI with stent implantation at 15 clinical sites in five countries between July 2009 and December 2010.
Follow-up at 30 days, six months, one, and two years determined whether patients had discontinued, interrupted, or disrupted antiplatelet therapy and whether this resulted in any major adverse cardiovascular events (MACE).
“Discontinuation” was defined as a physician-recommended cessation of medication for subjects believed to no longer need it, while “interruption” was defined as temporary (up to 14 days) due to surgical necessity, and “disruption” was due to bleeding or non-compliance.
In a final analysis of 5,018 patients at two years, the study showed a cumulative incidence of discontinuation, interruption, and disruption of 40.8 percent, 10.5 percent, and 14.4 percent, respectively, while the cumulative incidence of MACE was 11.5 percent.
At one-year, which is the duration currently recommended for antiplatelet therapy, the cumulative incidence of discontinuation, interruption, and disruption was 11.5 percent, 4.6 percent, and 9.8 percent respectively, with a 7.4 percent cumulative incidence of MACE.
The majority of MACE (74 percent) occurred in patients who had remained on their recommended antiplatelet therapy, but among those who had not, there was a 50 percent increased risk of MACE associated with disrupting compared to staying on medication, and a 37 percent decreased risk associated with discontinuation compared to staying on. In contrast, brief interruptions did not increase risk for thrombotic events such as stent thrombosis or myocardial infarction.
“The findings show that when physicians recommend discontinuation presumably because patients are stable, there is no risk of adverse events, but when patients simply don’t comply or are forced off antiplatelet therapy because they are bleeding, their risk is significantly elevated,” said Mehran.
For the latter group, a novel finding was that the risk of MACE was highest in the first seven days of disruption (when there was a seven-fold increase), after which it decreased.
Importantly, the study also showed that sustained antiplatelet therapy was not associated with reduced thrombotic risk compared to recommended discontinuation — a finding that goes against common assumption.
“In fact, there was a slight, though statistically non-significant reduction in risk associated with recommended discontinuation, which contrasts with some previous studies that have suggested a potential protective effect with prolonged antiplatelet therapy,” she said.
The PARIS study results show that the effect of antiplatelet cessation on cardiovascular risk is “modest” offering insight on this interaction in the modern era of post-PCI therapy.
Previous studies have not included such a broad range of subjects and did not account for the context around antiplatelet cessation, according to Mehran.
“We hope that these novel findings will spur initiatives to standardize and harmonize criteria for DAPT cessation, analogous to previous efforts used for myocardial infarction and bleeding.”
The PARIS study was supported by a Mount Sinai investigator-initiated grant from Bristol Myers Squib/Sanofi-Aventis. Representatives of the funding agency were not directly involved in the collection, management, analysis or interpretation of the data.
For more information www.mountsinai.org