Individualised dual antiplatelet therapy in PCI patients can minimise early ischaemic events
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
BackgroundObservational 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 . 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) . 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 .
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).
- 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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ConclusionThis 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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