Tailoring dual antiplatelet therapy duration for an individual patient

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Drug-eluting stents are becoming the default strategy of percutaneous coronary intervention (PCI). Despite a significant reduction in the recommended duration of dual antiplatelet therapy, the optimal duration remains to be determined—in particular for patients at high risk of ischaemic or bleeding events. Guillaume Cayla explores how, in clinical practice, the duration of DAPT may be tailored after careful evaluation of both bleeding and ischaemic risk, taking into consideration the type of the device implanted.

Stent thrombosis continues to be a relevant issue that needs to be prevented by antiplatelet therapy. Several factors have been associated with occurrence of this complication, such as procedural, lesion, device, platelet factor and patient factors. One of the most important predictors of stent thrombosis remains the clopidogrel cession within the first month. As a result, one of the main objectives of dual antiplatelet therapy is to reduce occurrence of stent thrombosis.

Bleeding is a very frequent complication of dual antiplatelet therapy (DAPT). Several factors have been associated with bleeding complications such as female gender, low body weight, elderly, history of bleeding, renal insufficiency, and oral anticoagulation.

To answer the question about tailoring of DAPT after PCI, we must address a key question: why are we giving DAPT in coronary artery disease and is this for the patient or for the stent? 

Firstly, with respect to the patient, in the setting of acute coronary syndromes, 12 months duration of DAPT is still recommended1 corresponding to the duration tested in pivotal trails such as CURE (Clopidogrel in unstable angina to prevent recurrent events), TRITON (Prasugrel versus clopidogrel in patients with acute coronary syndromes) and PLATO (Ticagrelor versus clopidogrel in patients with acute coronary syndromes). After the negative results of the CHARISMA study,2 the majority of patients had to stop clopidogrel 12 months after PCI and only a small proportion of selected patients at a high risk of ischaemic events and without an excessive risk of bleeding could be treated beyond 12 months. On the other hand, a systematic reduction of DAPT is proposed for patients on oral anticoagulation.

Regarding the stent, new generations of drug-eluting stents offer significant technical improvements of the characteristics of stents like the use of thinner strut thickness, biodegradable polymer and better drug release. Several randomised trials, such as the recent ARCTIC (Dual-antiplatelet treatment beyond one year after drug-eluting stent implantation) interruption trial,3 have shown that longer duration of DAPT (ie. >12 months) is not associated with a reduction of ischaemic events with an increased risk of bleeding complications. However all these studies have an important limitation: the physicians did not randomise patients at a high risk of ischaemic complications and, therefore, data are lacking for this population. Data from observational studies suggests that very short duration of DAPT (ie. one month) can be safely used with new generation of drug-eluting stents without an increased risk of stent thrombosis or ischaemic complications. The ongoing SENIOR (Short Duration of DAPT with Synergy II stent in patients older than 75 years undergoing percutaneous coronary revascularisation) and LEADER FREE (a randomised double-blind comparison of the BioFreedom drug-coated stent vs. the Gazelle bare metal stent in patients at high bleeding risk using a short [one month] course of DAPT) trials will give more data from randomised trials using a very short duration of DAPT in patients at a high risk of bleeding.

The optimal duration of DAPT after bioresorbable scaffold implantation is still a matter of debate. The thickness of the strut (150mm), and the length of resorption (24 to 36 months) suggests that duration or DAPT after may be longer in comparison with new drug-eluting stents. Data from the recent GHOST-EU (Gauging coronary Healing with bioresorbable scaffolding platforms in Europe) registry4 suggest that stent thrombosis is still an important issue with the device. As a consequence, data are needed to determine the optimal duration of DAPT after bioresorbable vascular scaffold implantation.

 

References

  1. Windecker et al. EuroIntervention 2014
  2. Bhatt et al. N Engl J Med 2006; 354: 1706–17
  3. Collet et al. Lancet 2014
  4. Capodanno D et al. EuroIntervention 2014

Guillaume Cayla, CHU Caremeau, Service de Cardiologie, CHU de Nîmes, France, ACTION GROUP, Paris, France