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New DAPT score identifies patients who may benefit from extended therapy
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ORLANDO, Fla. — Based on the cohort from the DAPT study, a score has been created that may help clinicians determine who should and should not receive dual antiplatelet therapy for more than 1 year after stenting.
In patients who have not had a major bleeding event or ischemic event in the first year after PCI with stenting, a score of less than 2 indicates that bleeding risk may outweigh ischemic benefit of long-term DAPT, and a score of 2 or more indicates that ischemic benefit may outweigh bleeding risk, Robert W. Yeh, MD, MSc, MBA, said during a press conference at the American Heart Association Scientific Sessions.
Robert W. Yeh
The DAPT Score calculator is available to the public at http://www.daptstudy.org, he said.
In the main results of the DAPT study (n = 11,648), DAPT beyond 1 year was associated with a decrease in ischemic events but an increase in bleeding events and a nominal increase in all-cause mortality compared with aspirin alone in patients who were stable after stenting, Yeh said.
Decision tool developed
“While these results reflect the average treatment effects observed in the population, there may be some individuals who derive greater overall benefit from extended [DAPT] treatment, while others derive overall harm,” Yeh, director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, said. “Therefore, the goal of this analysis was to develop a decision tool to identify whether an individual patient is more or less likely to derive benefit or harm from continuation of [DAPT] beyond 1 year. Our goal here was to simultaneously account for the risks of ischemia and bleeding to inform overall treatment benefit.”
The researchers developed separate prediction models for ischemic events and bleeding events within the DAPT cohort and validated them within the PROTECT study population. “In the ischemic model, we identified predictors of [MI] and stent thrombosis, including fatal events,” Yeh said. “In the bleeding model, we identified predictors of GUSTO moderate or severe bleeding, including fatal bleeds.”
From those models, the researchers could predict four numbers for each patient: predicted ischemic event rate with placebo, predicted ischemic event rate with treatment, predicted bleeding event rate with placebo and predicted bleeding event rate with treatment, he said.
The difference between the two ischemic numbers produced the predicted risk reduction in ischemic events and the difference between the bleeding numbers produced the predicted risk increase in bleeding events. Subtracting the predicted risk increase in bleeding events from the predicted risk reduction in ischemic events produced the predicted net treatment effect, he said.
Independent predictors
Age per 10 years was an independent predictor of bleeding, while MI at presentation, prior MI or PCI, congestive HF or left ventricular ejection fraction < 30%, vein graft PCI, stent diameter < 3 mm, use of paclitaxel-eluting stents, smoking and diabetes were independent predictors of ischemia, Yeh said. Hypertension, peripheral artery disease and renal insufficiency were independent predictors of both, and because they had little impact on the net treatment effect, they were eliminated from the DAPT Score, he said.
From there, researchers derived the DAPT Score as follows: ˗2 for age 75 years or older; ˗1 for age 65 to 74 years; 0 for age less than 65 years; 1 for diabetes; 1 for current smoking; 1 for prior MI or PCI; 2 for congestive HF or LVEF < 30%; 1 for MI at presentation; 2 for vein graft PCI; and 1 for stent diameter < 3 mm, he said.
“When we look at the observed outcomes between randomized treatment arms as stratified by DAPT Score, we see a clear gradient of effect,” Yeh said. “As you go up in increasing DAPT Score, there is a clear greater reduction in stent thrombosis and MI. Simultaneously, moving in that same direction, you get less of an adverse impact on bleeding with continued thienopyridine vs. placebo. This same gradient was observed for the overall mortality results, where the increase in mortality associated with continued therapy was isolated to the low DAPT Score groups. In the result of the impacts on bleeding and ischemia, one can observe that net adverse events were increased with continued therapy in values in the first and second quartiles, but significantly decreased in the [third and fourth] quartiles of DAPT Score.”
The first and second quartiles had a DAPT Score of < 2, while the third and fourth had a score of ≥ 2, and those define the treat vs. no-treat groups, he said.
Patients with DAPT Score ≥ 2 had greater reduction in MI or stent thrombosis (P < .001), smaller increases in bleeding (P = .02) and fewer net adverse events (P < .001) compared with those with DAPT Score < 2, Yeh said, noting that the differences remained after eliminating those with paclitaxel-eluting stents, which are rarely used anymore in U.S. clinical practice.
“Among patients who have not had a major ischemic event or bleeding event in the first year after PCI, the DAPT Score identified patients for whom ischemic benefits outweighed bleeding risks, and other patients for whom bleeding risks outweighed ischemic benefits,” Yeh said. “Among low DAPT Score patients, continuing thienopyridine therapy would be 2.5 times more likely to cause bleeding than to prevent stent thrombosis or [MI] compared to high DAPT Score patients, in which continuing therapy would be eight times more likely to prevent [MI] than to cause a bleeding event.”– by Erik Swain
Reference:
Yeh RW. Late-Breaking Clinical Trials 3. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: The DAPT study was funded in part by Abbott, Boston Scientific, Bristol-Myers Squibb/Sanofi, Cordis, Daiichi Sankyo, Eli Lilly and Medtronic. The present analysis was supported by the NHLBI and Harvard Clinical Research Institute. Yeh reports receiving personal fees from Abbott Vascular, Boston Scientific and Merck.
Perspective
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James A. de Lemos, MD
A very straightforward clinical message emerges from this analysis: For those 50% of individuals with a DAPT Score ≥ 2, there is clear net benefit with extending the duration of DAPT. For the subgroup with a score < 2, there is also a clear message: There is harm in extending the duration. This is an important study and a major step forward.
A couple of caveats: The score is generalizable only to a DAPT study-like population of stable patients who have tolerated 1 year of DAPT, and the study did not include patients receiving oral anticoagulants. Replication is definitely necessary. The models in this study were fit to the specific dataset, and there were a couple of surprising features, including the fact that only one bleeding variable emerges, and that there is a monotonic association across scores of bleeding. There are likely not a large number of datasets that would be suitable for evaluating this, but PEGASUS may be one of them.
As Dr. Yeh suggested, the model discrimination was only moderate, but in point of fact is comparable to other clinical scores used widely in CV practice, including the CHA2DS2-VASc score.
This offers a data-derived personalized medicine tool. There has been so much attention on precision medicine using complex genetic or biomarker tools, but this study elegantly demonstrates the power of clinical variables in personalized medicine. Moreover, it offers a simple and practical solution to a daily clinical problem for practicing cardiologists and physicians.
This completely revises my interpretation of the DAPT result. I considered the trial essentially null based on the tradeoff of risk and benefit and the importance of the bleeding complications. But we see now a much more clearly favorable benefit-to-risk profile for a substantial subset of patients who had PCI. It’s likely that the models in this score can be further optimized with additional study.
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