The Long and Short of It: DAPT Duration Choice After Stenting Gets Help From New Score
The PRECISE-DAPT score incorporates five readily available variables to identify patients who have a high bleeding risk in the first year after PCI.
A newly developed tool—called the PRECISE-DAPT score—enables the identification of patients who have a high risk of out-of-hospital bleeding in the year after PCI, potentially easing individualized decisions regarding the duration and type of dual antiplatelet therapy (DAPT).
The score, which can be derived using an online calculator (the mobile app is forthcoming), takes into account five readily available clinical factors—age, creatinine clearance, hemoglobin, white blood cell count, and bleeding history.
The tool had moderate discriminatory ability in a derivation cohort and two validation cohorts that included patients undergoing PCI for various indications who were treated with DAPT that incorporated clopidogrel, ticagrelor (Brilinta; AstraZeneca), or prasugrel (Effient; Eli Lilly), report lead author Francesco Costa, MD (Bern University Hospital, Switzerland), and colleagues in a study published in the March 11, 2017, issue of the Lancet.
“We have had many prognostic stratification tools in our practice which nobody has ever used, and the reason why nobody has ever used them is because the results of these classification tools are not really impacting practice,” senior author Marco Valgimigli, MD (Bern University Hospital), told TCTMD.
PRECISE-DAPT, on the other hand, provides actionable results that can be used as part of a clinical evaluation to determine the most appropriate DAPT course, he said. In patients with a high bleeding risk, “of course you should be mindful of trying to minimize that bleeding as much as you can,” he said, “whereas in a patient in whom the bleeding risk is not that high, probably you can be more liberal in giving long-term and even more potent antithrombotic therapy.”
Commenting for TCTMD, Donald Cutlip, MD (Beth Israel Deaconess Medical Center, Boston, MA), agreed with Valgimigli that that’s where the value of the PRECISE-DAPT score lies. “That’s the question we’re trying to address,” he said. “Do we need to put these patients on long-term therapy or do we really have to think about shorter-term therapy because of the bleeding risk. I think the score is useful for that.”
Cutlip said it’s hard to predict whether the tool will be adopted widely in clinical practice, noting that clinicians already routinely consider some of the included variables—such as age, creatinine clearance, and bleeding history—when making decisions about DAPT. “We know patients who are older and patients who have renal dysfunction or a previous history of bleeding are more likely to bleed, and I think the current practice is already to treat those patients probably with shorter-term dual antiplatelet therapy,” he said. “But having it quantified in a well-done clinical study is useful, and this score could be used.”
No Ischemic Benefit of Longer DAPT in High-Risk Patients
The optimal duration of DAPT is an area of active research and debate, with guidelines generally allowing clinicians flexibility to personalize treatment based on ischemic and bleeding risks. There is no standard single tool to help in that decision, however.
To develop the PRECISE-DAPT score, the investigators pooled individual patient-level data from eight multicenter clinical trials that included a total of 14,963 patients treated with DAPT after stenting; the P2Y12 inhibitor combined with aspirin was clopidogrel in most cases. Patients with an indication for oral anticoagulation were excluded.
The researchers looked for predictors of out-of-hospital TIMI major or minor bleeding occurring at least 7 days after the initial procedure. The rate of out-of-hospital TIMI major or minor bleeding occurring 7 days to 1 year after the initial procedure was 12.5 per 1,000 patients and was most strongly associated with the five variables included in the risk score:
- Previous spontaneous bleeding: HR 4.14 (95% CI 1.22-14.02)
- Age: HR 1.34 (95% CI 1.11-1.48) per 10-year increase
- White blood cell count: HR 1.06 (95% CI 0.99-1.13) per increase of 103 cells/µL
- Creatinine clearance: HR 0.90 (95% CI 0.82-0.99) per increase of 10 mL/min
- Baseline hemoglobin: HR 0.67 (95% CI 0.53-0.84) per increase of 1 g/dL
The score had moderate discriminatory value for 1-year bleeding, with a c-index of 0.73. The finding was consistent regardless of clinical presentation at the time of PCI or treatment with clopidogrel or ticagrelor, although performance seemed to be slightly worse for prasugrel-treated patients and better for those treated with proton pump inhibitors.
Performance in two validation cohorts—the PLATO trial and the BernPCI registry—was similar, with c-indices of 0.70 and 0.66, respectively. The PRECISE-DAPT score improved integrated discrimination and reclassification performance compared with the previously published PARIS bleeding risk score in both of those cohorts.
The researchers further examined outcomes associated with different durations of DAPT in patients classified as having high or non-high bleeding risks. In patients at high risk, a DAPT duration of 12 to 24 months was associated with more bleeding but no ischemic benefit compared with a duration of 3 to 6 months. In contrast, patients without a high bleeding risk derived an ischemic benefit from longer-duration DAPT, without an increase in bleeding.
“Selecting up front a shorter than 12-month treatment duration in patients deemed at high bleeding risk (PRECISE-DAPT score ≥ 25) might prevent exposing them to an excessive bleeding hazard,” the authors write. “In turn, patients at non-high bleeding risk (PRECISE-DAPT score < 25) might receive a standard (ie, 12 months) or a prolonged (ie, > 12 months) course of treatment if tolerated.”
How PRECISE-DAPT Fits With Other Scores
PRECISE-DAPT adds to several previous risk scores that have been developed to help stratify patients. Two separate scores from the PARIS registry, for example, assess ischemic and bleeding risks in an all-comers PCI population. In addition, the DAPT score aids clinicians in determining which patients who complete 1 year of DAPT without complications may benefit from prolonging treatment.
“At variance with our analysis, the PARIS study did not provide a decision-making algorithm for deciding upon DAPT duration,” Costa et al write. “With respect to bleeding risk prediction, our score ultimately proved at least as good as PARIS, showing improved integrated discrimination and net reclassification, whereas c-indices were numerically but not always statistically superior.”
As for the DAPT score, because it cannot be used to establish the appropriate duration of therapy before 1 year, it is complementary to the PRECISE-DAPT score, Valgimigli said.
What remains to be seen, he added, is whether using PRECISE-DAPT to guide DAPT duration has an impact on patient outcomes. Funding has not yet materialized for such a prospective trial, he said.
In an accompanying editorial, Davide Capodanno, MD, PhD (University of Catania, Italy), and Dominick Angiolillo, MD, PhD (University of Florida, Jacksonville), call PRECISE-DAPT “practical and user-friendly” and say that it may have use beyond simply selecting DAPT duration.
“This kind of early risk assessment might be a timely factor in decision making for other bleeding avoidance strategies, such as selection of vascular access, stent, or drugs,” they write.
But Capodanno and Angiolillo also note the limitations of using a risk tool.
“Importantly, categorizing a patient as having high bleeding risk is challenged by the notion that the risk for bleeding is dynamic and might change over time, a process that cannot necessarily be accounted for when limited to in-hospital criteria,” they say. “As such, clinicians must remain aware and vigilant that risk scores, like PRECISE-DAPT, although useful to improve the accuracy of the prognostic assumptions affecting clinical decisions, cannot be considered a clear-cut decision rule or a substitute for case-by-case critical judgment.”
Costa F, van Klaveren D, James S, et al. Derivation and validation of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025-1034.
Capodanno D, Angiolillo DJ. Tailoring duration of DAPT with risk scores. Lancet. 2017;389:987-989.
- Valgimigli reports receiving research grants from The Medicines Company, Terumo, and AstraZeneca.
- Costa and Cutlip report no relevant conflicts of interest.
- Capodanno reports receiving consulting fees or honoraria from AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly, and The Medicines Company.
- Angiolillo reports receiving consulting fees or honoraria from Abbott Vascular, Amgen, AstraZeneca, Bayer, Chiesi, Daiichi Sankyo, Eli Lilly, Merck, Pfizer, PLx Pharma, Sanofi, and The Medicines Company; participating in review activities for Johnson & Johnson and St. Jude Medical; and receiving institutional payments for grants from Amgen, AstraZeneca, CSL Behring, Daiichi Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, Osprey Medical, and The Medicines Company.