Δοκιμασίες λειτουργικότητας αιμοπεταλίων και PCI

Transcription

1 Δοκιμασίες λειτουργικότητας αιμοπεταλίων και PCI Ομάδες Εργασίας Φεβρουάριος 2016 Ξανθοπούλου Ιωάννα Καρδιολόγος Επιμ Β ΠΓΝΠατρών

2 Nothing to disclose

3 Platelet function testing (PFT) is helpful in identifying patients at high risk for: Ischemic events Bleeding events

4 A total of 6 studies with 3,059 patients was included. A PRU value 230 was associated with a higher rate of the composite primary endpoint (HR: 2.10; 95% CI: 1.62 to 2.73; p

5 ADAPT-DES Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents 11,000 DES pts prospectively enrolled No clinical or anatomic exclusion criteria 11 sites in US and Germany PCI with 1 non-investigational DES Successful and uncomplicated (IVUS/VH substudy; Up to 3000 pts enrolled) Assess platelet function after adequate DAPT loading and GPI washout: Accumetrics VerifyNow Aspirin, VerifyNow P2Y12, and VerifyNow IIb/IIIa assays (results blinded) Clinical FU at 30 days, 1 year and 2 years Angio core lab assessment all STs w/1:2 matching controls clinicaltrials.gov NCT

6 ADAPT-DES: Stent thrombosis (definite or probable) according to post-pci PRU Stent thrombosis (def/prob) (%) 2 PRU >208 (n=3610) PRU 208 (n=4839) Adjusted HR [95%CI] =2.49 [1.43, 4.31] P= % 1 0.5% Number at risk: PRU > 208 PRU Months

7 Platelet function testing (PFT) is helpful in identifying patients at high risk for: Ischemic events Bleeding events

8 Patients (n = 2533) undergoing PCI after pretreatment with 600 mg of clopidogrel were enrolled in this study. Blood was obtained directly before PCI. The risk of a major bleeding was significantly higher in patients with response to clopidogrel (<188 AU min): adjusted OR 3.5, 95% CI , P =

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11 These patients should have better outcomes! Udaya S. Tantry et al. Consensus and Update on the Definition of On-Treatment Platelet Reactivity to Adenosine Diphosphate Associated With Ischemia and Bleeding (J Am Coll Cardiol 2013;62: )

12 Platelet function testing (PFT) is helpful in identifying patients at high risk for: Ischemic events Bleeding events Treatment modification according to PFT failed to show clinical benefit

13 GRAVITAS Study Design Elective or Urgent PCI with DES* VerifyNow P2Y12 Test hours post-pci PRU 230 R High-Dose Clopidogrel clopidogrel 600-mg, then clopidogrel 150-mg daily X 6 months Standard-Dose Clopidogrel clopidogrel 75-mg daily X 6 months Primary Efficacy Endpoint: CV Death, Non-Fatal MI, Stent Thrombosis at 6 mo Key Safety Endpoint: GUSTO Moderate or Severe Bleeding at 6 mo Pharmacodynamics: Repeat VerifyNow P2Y12 at 1 and 6 months *Peri-PCI clopidogrel per protocol-mandated criteria to ensure steady-state at hrs placebo-controlled All patients received aspirin (81-162mg daily)

14 Primary Endpoint: CV Death, MI, Stent Thrombosis Observed event rates are listed; P value by log rank test.

15 Early termination due to low event rate

16 ARCTIC trial design Coronary angiogram Rd VerifyNow P2Y12 + ASA Drug (ASA, clopidogrel, prasugrel, GP2b3a I.) and Dose adjustments if high platelet reactivity Stent-PCI Drug and Dose adjustments if high platelet reactivity at Day month FU Standard of care Stent-PCI Standard of care Primary endpoint at 12 months: Death, MI, stroke, stent thrombosis, urgent revascularization Statistical considerations: Assuming an annual risk of 9% and a 33% relative risk reduction (α risk at 5% and error β of 20%, bilateral test), 2,466 patients were necessary to demonstrate the superiority of the strategy of monitoring and adjustment ARCTIC study protocol - Collet JP, et al. Am Heart J 2011;161:5-12

17 Primary Endpoint to 1 year Death, MI, stroke, stent thrombosis, urgent revascularization Monitoring Conventional HR = 1.13 [ ] p= % 31.1%

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19 A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and 50% shorter waiting time than recommended in the current guidelines.

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21 PFT may be considered.. In clopidogrel-treated ACS patients with risk for bleeding and risk for thrombotic events: patients without HPR to clopidogrel may continue clopidogrel treatment. due to limited availability of prasugrel or ticagrelor: patients with HPR should be switched to prasugrel/ticagrelor. In clopidogrel-treated stable CAD patients with: Stent thrombosis (ST) risk for ST (unsatisfactory PCI results, complex interventions in high-risk patients) ST would be of catastrophic consequences (last remaining vessel PCI, left main PCI involving the bifurcation) patients with HPR might be switched to novel agent

22 Usefulness of PFT in influencing therapeutic management deserves further evaluation Previous studies included low-risk population or were not enough powered based on the observed event-rate large multi-centre studies, powered for ischemic endpoints, involving patients at high risk for stent thrombosis (preferably AMI) High-dose clopidogrel was used to intensify platelet inhibition prasugrel or ticagrelor to intensify platelet inhibition

23 Thank you for your attention!