Physicians' Academy for Cardiovascular Education

Individualised dual antiplatelet therapy in PCI patients can minimise early ischaemic events

Literature - Christ G et al., BMJ Open. 2014

 

Individualising dual antiplatelet therapy after percutaneous coronary intervention: the IDEAL-PCI registry.

 
Christ G, Siller-Matula JM, Francesconi M, et al.,
BMJ Open. 2014 Oct 31;4(10):e005781. doi: 10.1136/bmjopen-2014-005781
 

Background

Observational studies have suggested that high on-treatment platelet reactivity (HPR) to adenosine diphosphate (ADP) is a strong independent risk factor for ischaemic events in patients given dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) [1-3].
It is as yet unclear and topic of debate whether HPR is a marker of higher risk, or a modifiable risk factor [2]. Studies to date evaluating personalised antiplatelet therapy to aiming to overcome HPR have yielded conflicting results, and methodological limitations may have masked the value of this strategy [1,4].
HPR to acetylic salicylic acid (ASA) is less well studied. ADAPT-DES registry data showed no difference in response to ASA, as measured with the VerifyNow assay, between patients with and without stent thrombos (ST) [3]. Other data suggests, however, that dual HPR to ADP-induced and arachidonic acid-induced (AA: reflecting response to ASA) aggregation predisposes patients to a higher ischaemic risk than single HPR. Multiple electrode aggregometry (MEA) can effectively assess the risk of HPR to ADP after PCI [5].
This tertiary care single centre registry was used to evaluate the impact of individualising DAPT with MEA in an all-comers population, including STEMI patients, by peri-interventional treatment of HPR to ADP and AA. Outcomes were compared between a group that did not have HPR after clopidogrel loading (non-HPR), and the individualised group (ADP receptor blocker reloading and primary prasugrel or ticagrelor loading, based on a logarithm).

 
Main results

  • 30% of clopidogrel loaded patients showed HPR.
  • After ASA and ADP receptor blocker loading, 9% of patients showed HPR to AA-induced aggregation. HPR to AA was significantly more prevalent in patients with HPR to ADP (22% vs. 4%, P<0.001).
  • HPR to AA without HPR to ADP (63+29 U) was successfully treated by ASA reloading in all patients (14+6 U, P<0.001).
  • In patients with HPR to ADP, the extent of the residual AA-induced platelet aggregation influenced HPR to AA.
  • ADP-induced aggregation after 600 mg clopidogrel loading was significantly higher in patients with HPR (=non-responder: 73+19 U) than in patients without HPR (=responder: 28+11 U, P<0.001). Reloading effectively treated HPR (22+12 U, P<0.001), in all but two patients for whom prasugrel was not yet available.
    ADP-induced aggregation after 60 mg prasugrel loading was significantly higher in patients with HPR (=non-responder: 82+26 U) than without (=responder: 19+ U, P<0.001), and was successfully treated with ticagrelor reloading (35+15 U, P=0.002).
  • Glycoprotein IIbIIIa inhibitor (GPI) treatment was given to 61% (n=57) of STEMI patients, and in 11% (n=47) of NSTEMI patients.
  • No acute ST is occurred within 24 hours in the whole patient cohort. Only one subacute definite ST occurred within 30 days (0.09%). No increase in bleedings was seen in individualised patients (2.6% TIMI major and minor bleedings in both groups).

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Conclusion

This study provides real-world evidence that routine efficient peri-interventional individualisation of DAPT with MEA, and use of newer generations of ADP receptor blockers, can minimise early ischaemic events after PCI in an all-comers population including STEMI patients. Intensifying platelet inhibition in patients with HPR did not increase bleeding complications, as compared with patients without HPR under DAPT. ADP-dependent and ASA-dependent platelet activation may act synergistically. These data therefore suggest that HPR is a modifiable risk factor to which treatment in PCI patients can be tailored.
 
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References

1. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to ADP associated with ischemia and bleeding. J Am Coll Cardiol 2013;62:2261–73.
2. Aradi D, Storey RF, Komócsi A, et al.; on behalf of the Working Group on Thrombosis of the European Society of Cardiology. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014;35:209–15.
3. Stone GW, Witzenbichler B, Weisz G, et al.; for the ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 2013;382:614–23.
4. Siller-Matula JM, Jilma B. Why have studies of tailored anti-platelet therapy failed so far? Thromb Haemost. 2013;110:628–31.
5. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009;53:849–56.
 
 

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