The impact of nonadherence to DAPT was further illustrated in a study by Dr Cutlip and colleagues published in JACC: Cardiovascular Interventions in March 2015.4 This prospective observational study explored the effect of early and late nonadherence to DAPT in patients undergoing coronary stenting with a second-generation DES, the Endeavor zotarolimus-eluting stent (Medtronic Vascular, Santa Rosa, CA). Following implantation, 2265 patients were monitored for 12 months of prescribed DAPT. Results showed an increased risk of death or myocardial infarction (MI) for patients with any nonadherence (ANA) to DAPT within the first 6 months of prescription, compared with patients who were fully adherent for that duration.4

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Before 6 months, ANA was observed in 9.6% of patients; this number nearly doubled to 18.5% by 12 months. ANA after 6 months did not increase the risk of death or MI in patients fully adherent for the first 6 months.

Dr Cutlip told Cardiology Advisor factors that predict which patients have greater benefit vs risk for longer vs shorter DAPT durations are still being elucidated. “Given the serious adverse outcomes associated with bleeding, it is likely that shorter durations of DAPT will be better for net outcome,” he noted. “There is controversy regarding what this minimal duration should be for newer-generation drug-eluting stents. We don’t have great data, since the randomized trials of short duration (as low as 3 months) were limited by inclusion of low-risk populations and few events. Observational data suggest the risk continued for 6 months but is low after 6 months.”

“[What is] more clear is that the risk is high if both agents are stopped. In other words, if the P2Y12 inhibitor course has been completed and then aspirin is also stopped, then the risk probably continues for a much longer time period. For this reason, we are reluctant to approve of discontinuing aspirin even beyond 12 months.”

Another study, conducted by Dr Rajendra H. Mehta and colleagues at the Duke Clinical Research Institute, examined hospital adherence to ACC/AHA guideline-recommended therapies, dosing safety as measured by the proportion of patients who received guideline-concordant doses of heparin or glycoprotein IIb/IIIa antagonists, and the effect of these adherence and safety metrics on in-hospital mortality and bleeding.5 The researchers found a significant correlation between a hospital’s composite guideline adherence rates and unadjusted in-hospital mortality. For every 10% increase in composite adherence at a center, a patient’s in-hospital mortality odds ratio (OR) fell by a corresponding 39% (OR 0.61; 95% confidence interval [CI], 0.50-0.75). Similarly, for every 10% increase in appropriate dosing at a center, a patient’s in-hospital mortality OR fell by a corresponding 18% (OR 0.82; 95% CI, 0.73-0.93). At 85%, median adherence to ACC/AHA guideline-recommended therapies was not perfect but high. In contrast, the median for antithrombotic dosing safety was only 53%.1,5

Communicating  Risks of Nonadherence

According to Dr Cutlip, patients should be informed about the minimum duration of antiplatelet therapy being prescribed and the risks associated with nonadherence. “This must be communicated clearly to the patient and the physicians who will provide ongoing follow-up. Another important area is advising preoperative clinics and our surgical and other procedural colleagues regarding the risks of routine protocols that mandate discontinuing aspirin or other antiplatelet therapy for elective procedures.”  


  1. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary. J Am Coll Cardiol. 2014;64(24):2645-2687. doi:10.1016/j.jacc.2014.09.0
  2. Chowdhury R, Khan H, Heydon E, et al. Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013; 34:2940-2948.
  3. Dewilde WJ, Oirbans T, Verheugt FW, et al; for the WOEST Study Investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-1115. doi: 10.1016/S0140-6736(12)62177-1.
  4. Cutlip DE, Kereiakes DJ, Mauri L, et al; for the EDUCATE Investigators. Thrombotic complications associated with early and late nonadherence to dual antiplatelet therapy. JACC Cardiovasc Interv. 2015;8(3):404-410. doi: 10.1016/j.jcin.2014.10.017.
  5. Mehta RH, Chen AY, Alexander KP, Ohman EM, Roe MT, Peterson ED. Doing the right things and doing them the right way: association between hospital guideline adherence, dosing safety, and outcomes among patients with acute coronary symptoms. Circulation. 2015;131(11):980-987. doi: 10.1161/CIRCULATIONAHA.114.031451.