ADAPT-DES Substudy: Practice Changes May Decrease Already Low Stent Thrombosis Rates Even Further
After successful DES implantation, stent thrombosis occurs in about 1 in 100 patients within 2 years, according to a substudy of the ADAPT-DES trial published online September 28, 2015, ahead of print in Circulation: Cardiovascular Interventions. However, the strong association between risk and modifiable factors suggests the potential to further decrease the prevalence of stent thrombosis.
ADAPT-DES included more than 8,000 patients presenting with stable CAD (48.3%) or ACS (51.7%) treated with DES and routine platelet reactivity testing (VerifyNow; Accriva Diagnostics) between 2008 and 2010. It found that early stent thrombosis in this population can be effectively predicted by absolute and relative levels of platelet inhibition and that the risk of late stent thrombosis increases with time.
For the substudy, Bruce R. Brodie, MD, of LeBauer Cardiovascular Research Foundation/Cone Health (Greensboro, NC), and colleagues looked deeper into potential risk factors for stent thrombosis. They observed stent thrombosis within 2 years in 92 patients (1.1%), including 72 definite and 20 probable cases. Among those cases, 42.4% were early (≤ 30 days), 35.9% were late (> 30 days to 1 year), and 21.7% were very late (> 1 year through 2 years).
Independent baseline predictors of stent thrombosis were ACS presentation, insulin-treated diabetes, previous MI, and PAD. Risk factors related to treatment were use of early-generation DES, no procedural IVUS, and premature discontinuation of dual antiplatelet therapy (DAPT). There was a trend toward increased risk of stent thrombosis in patients with high platelet reactivity on clopidogrel (table 1).
Patients who developed stent thrombosis had high rates of both cardiovascular death (30.0%) and nonperiprocedural MI (87.2%) at 2 years. These rates were similar regardless of ACS status.
The risk of developing stent thrombosis within 2 years ranged from 0.3% to 10.0% depending on whether patients had 0 or 3 risk factors—this impact was greater in ACS patients.
Breaking Down What’s Modifiable
“The fixed correlates of 2-year [stent thrombosis] in our study were consistent with the findings from… prior studies, which primarily evaluated early-generation DES,” the investigators write.
Dr. Brodie told TCTMD in a telephone interview that what makes this analysis “unique” is its insight into modifiable risk factors. “Those are something that we can do something about,” he stressed.
“The implication is if they can control all of these modifiable risk factors, they can dramatically reduce the risk of stent thrombosis,” Dr. Brodie said, adding that the use of early-generation stents is no longer an issue because new-generation DES have become standard of care.
“The good news is that the frequency of stent thrombosis has decreased” even more since the advent of new-generation DES, Dr. Brodie said. Even so, there is room for improvement, he noted. “IVUS guidance has not been used routinely, and I think this study hopefully will give increased incentive for people to use more IVUS in stent implantation [especially in high-risk patients].”
Whether or not patients comply with DAPT, he commented, is related to healthcare on a system-wide level. For example, a patient without insurance may not be able to afford his or her prescriptions, which often leads to early discontinuation. That being said, patient education should also be more of a priority, Dr. Brodie suggested. “We’re not doing as well as we can, but I think that we’re making progress.”
A slightly more difficult challenge relates to patients with high platelet reactivity after clopidogrel loading, he said. “Right now, patients with ACS do better when they are put on the new antiplatelet agents like prasugrel and ticagrelor, and the standard-of-care indication is to use these new drugs in all patients with ACS,” Dr. Brodie commented. “But the real issue is whether patients who don’t have ACS and have high platelet reactivity after clopidogrel loading should be treated with these new drugs or not.”
Much of this is a balancing act since newer agents are associated with increased bleeding risks, he added. “At the same time, they reduce the risk of stent thrombosis,” Dr. Brodie noted, concluding that the patients “who would benefit most would be the ones who are at highest risk for stent thrombosis.” Future studies are needed to look at the tradeoff between ischemic risk and bleeding more precisely, he added.
Note: Several coauthors of the study are faculty and staff members of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Brodie BR, Garg A, Stuckey TD, et al. Fixed and modifiable correlates of drug-eluting stent thrombosis from a large all-comers registry: insights from ADAPT-DES. Circ Cardiovasc Interv. 2015;Epub ahead of print.
- ADAPT-DES: Risk of Early Stent Thrombosis in DES Predicted by Platelet Inhibition
- SCAAR: Lower Risk of Early, Late Stent Thrombosis with Newer DES vs BMS in STEMI
- SCAAR Confirms Low Very Late Stent Thrombosis Risk with Newer DES
- ADAPT-DES was sponsored by the Cardiovascular Research Foundation, with funding provided by Abbott Vascular, Accumetrics, Biosensors, Boston Scientific, Cordis, Daiichi-Sankyo, Eli Lilly, Medtronic, The Medicines Company, and Volcano.
- Dr. Brodie reports no relevant conflicts of interest.