Many of our patients are on at least one antiplatelet agent and almost all of our post percutaneous coronary intervention (PCI) patients are on dual antiplatelet therapy (DAPT). Some of our patients will be on these agents for 6 to 12 months, while others may be on them indefinitely. We prescribe these drugs to reduce the rates of stent-related thrombosis in both the short and long term, and we must weigh the risk of stent thrombosis against the risk of bleeding. This balancing act is not always straightforward. We estimate the risk of stent thrombosis by the quality of the post PCI angiogram and the thrombosis risk factors the patient carries (Table 1). We also need to estimate the risk of bleeding, which in the past, was almost always a qualitative assessment, but now with the development of the DAPT score, can be better quantitated. This tool will permit us to give the patient a better idea of risk and benefit for continued DAPT.
How was the DAPT Score Developed?
The DAPT score was developed to predict combined ischemic and bleeding risk for patients being considered for longer term, continued thienopyridine (P2Y12 receptor antagonists, e.g. clopidogrel [Plavix], ticagralor [Brilinta], prasugrel [Effient]) therapy in addition to aspirin beyond one year after coronary stent implantation. The DAPT score was developed from the DAPT Study1, a randomized trial in which patients were randomized to continued clopidogrel or prasugrel treatment, or placebo. Patients were not included if they had a heart attack, stent thrombosis, stroke, repeat revascularization, bleeding episode, or use of oral anticoagulants. They needed to have been adherent with their medications during the first year. All enrolled patients had a coronary stent procedure in which a drug-eluting stent was placed. Outcomes according to a clinical point system (now called the DAPT Score) were used only for patients not receiving a paclitaxel-eluting stent, since these stents are no longer commonly used. After 12 months of treatment (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; aspirin was continued in all patients. The study endpoints were stent thrombosis/myocardial infarction, major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) 12 to 30 months after the stent implantation, and GUSTO major bleeding episodes. The primary safety endpoint was moderate or severe bleeding.
What Did the DAPT Study Show?
A total of 9961 patients were randomly assigned to prolonged DAPT treatment or placebo. Compared to the 12-month treatment group (placebo), the prolonged treatment group had reduced the rates of stent thrombosis (0.4% vs 1.4%; P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of DAPT treatment. The study showed that antiplatelet therapy beyond 1 year after drug-eluting stenting, compared to aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events, but was associated with an increased bleeding risk (Figure 1).
Validation of the DAPT Score
Yeh et al2 developed and validated a prediction rule for assessing the risk vs benefit of prolonged dual antiplatelet therapy in 11648 randomized DAPT Study patients from 11 countries (August 2009-May 2014). A prediction rule was derived, stratifying patients into groups to differentiate ischemic and bleeding risk 12 to 30 months after PCI. Validation was obtained from an internal statistical model (called bootstrap resampling) and from an external sampling method among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014). The main outcomes and measures of ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) were tabulated over the 12 to 30 months after PCI. Among DAPT Study patients, ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had strong associations (c statistics of 0.70 and 0.68, respectively). The prediction rule assigned points for different presenting conditions: 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter <3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; −1 point for age 65 to younger than 75 years; and −2 points for age 75 years or older.
Among the high score group (score ≥2, n=5917), prolonged DAPT patients were associated with reduced ischemic events (2.7% vs 5.7%; P<.001) compared with the low score group (score <2, P<.001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; P=.26) compared with the low score group (3.0% vs 1.4%; P<.001). Among PROTECT patients (the validation cohort; with nearly the same age and sex distribution), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a similarly strong c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n=2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.
The authors concluded that among patients after an event-free first year after PCI, a prediction rule assessing late ischemic and bleeding risks for DAPT duration showed modest accuracy in both derivation and validation cohorts. This rule requires further prospective evaluation and validation in other cohorts.
The DAPT Risk Calculator Apps
Recently, the American College of Cardiology (ACC), among others, released the ACC DAPT Risk Calculator app to give the practitioner a tool for better decision support. For clinicians evaluating the continuation of DAPT therapy for patients at least 12 months post PCI procedure, this app gives an estimate in quantitative terms of the risk/benefit of continuing or discontinuing DAPT (Figure 2A-B). By inputting the clinical variables requested, the app provides a DAPT Risk Score as a numerical value between -2 and +9, where a higher DAPT scores suggest that the benefit/risk ratio with prolonged DAPT may be favorable. Conversely, lower DAPT scores suggest that the benefit/risk ratio with prolonged DAPT is NOT favorable. The app also calculates the percentage of risk for three endpoints: myocardial infraction (MI) and stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE), and bleeding.
For the most complicated patients in whom we are worried about the need for DAPT, because of numerous stents or prior in-stent restenosis treated again with stents, and the risk of bleeding with a prolonged treatment regimen, we should consider the risks using the DAPT app. While certainly no guarantee of success, such well-conceived tools should bolster our clinical judgment, and support our decisions to treat or not treat these difficult and sometimes delicate patients. Consider using these tools for your patients leaving the cath lab after your next complicated stent procedure.
- Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014 Dec 4; 371(23): 2155-2166.
- Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, et al; DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016; 315(16): 1735-1749.
Disclosure: Dr. Kern is a consultant for Merit Medical, Abbott Vascular, Philips Volcano, ACIST Medical, Opsens Inc., Boston Scientific Inc., and Heartflow Inc.