Διάρκεια διπλής αντιαιµοπεταλιακής αγωγής µετά από οξύ στεφανιαίο σύνδροµο Α. Ζιάκας, Αναπληρωτής Καθηγητής Καρδιολογίας Α.Π.Θ., Π.Γ.Ν. ΑΧΕΠΑ
ΑΣΠΙΡΙΝΗ - ΚΛΟΠΙΔΟΓΡΕΛΗ
How do we treat ACS? Is prolonging (>1-year) intensified antiplatelet therapy the answer?
CHARISMA-Prior MI Bhatt DL, Flather MD, Hacke W, et al. JACC 2007; 49:
Efficacy Early and Late Qualifying MI
DAPT STUDY
DAPT STUDY
DAPT Score: How to individualize therapy
DAPT STUDY Διαφορα στη θνητοτητα Καποιοι θανατοι ειχαν σχεση µε αιµορραγιες αλλα λιγοι Αλλοι οφειλονταν σε cancer αλλα δε σχετιζονταν µε το µηχανισµο των αντιαιµοπεταλιακων δηλαδη λιγοι ειχαν καρκινο που αιµορραγησε Τελος αυξηθηκαν οι bleeding-related trauma deaths in DAPT
PEGASUS-TIMI 54: Study Design Patients aged 50 years with a history of spontaneous MI 1 3 years prior to enrolment AND at least one additional atherothrombosis risk factor* (N=21,162) Ticagrelor 90 mg bid + ASA 75 150 mg/day Ticagrelor 60 mg bid + ASA 75 150 mg/day Placebo + ASA 75 150 mg/day Minimum of 12 months follow up: Every 4 months in Year 1, then semi-annually Primary efficacy endpoint: CV death, MI or stroke Primary safety endpoint: TIMI-defined major bleeding *Age 65 years, diabetes mellitus, second prior MI, multivessel CAD or chronic non-end stage renal disease bid, twice daily; CAD, coronary artery disease; TIMI, Thrombolysis in Myocardial Infarction Bonaca MP et al. Am Heart J 2014;167:437 444 Bonaca MP et al. N Engl J Med 2015;372:1791 1800 19
PEGASUS-TIMI 54: Inclusion Criteria one additional high-risk feature Age 65 years old Diabetes mellitus requiring medication A second prior spontaneous MI Angiographic evidence of multivessel CAD Chronic, non-end-stage renal dysfunction (CrCl <60 ml/ min) Prescribed and tolerating ASA at the time of enrolment 20
PEGASUS-TIMI 54: Primary Endpoint 10 9 8 Placebo Ticagrelor 90 mg bid Ticagrelor 60 mg bid 9.04% Placebo 7.85% 90 mg bid 7 7.77% 60 mg bid Event rate (%) 6 5 4 3 2 1 Ticagrelor 90 mg vs placebo HR 0.85 (95% CI 0.75 0.96) P=0.008 Ticagrelor 60 mg vs placebo HR 0.84 (95% CI 0.74 0.95) P=0.004 No. at risk Placebo 90 mg bid 60 mg bid 0 0 3 6 9 12 15 18 21 24 27 30 33 36 7067 7050 7045 6979 6973 6969 6892 6899 6905 P<0.026 indicates statistical significance; CI, confidence interval; HR, hazard ratio Bonaca MP et al. N Engl J Med 2015;372:1791 1800 6823 6827 6842 6761 6769 6784 Months from randomisation 6681 6719 6733 6508 6550 6557 6236 6272 6270 5876 5921 5904 5157 5243 5222 4343 4401 4424 3360 3368 3392 2028 2038 2055 21
PEGASUS-TIMI 54: Efficacy Endpoints Endpoint Primary CV death, MI or stroke (1558 events) CV death (566 events) MI (898 events) Stroke (313 events) 3-year KM event rates (%) Ticagrelor Placebo HR (95% CI) P value 7.85 9.04 0.85 (0.75 0.96) 0.008 7.77 9.04 0.84 (0.74 0.95) 0.004 7.81 9.04 0.84 (0.76 0.94) 0.001 2.94 3.39 0.87 (0.71 1.06) 0.15 2.86 3.39 0.83 (0.68 1.01) 0.07 2.90 3.39 0.85 (0.71 1.00) 0.06 4.40 5.25 0.81 (0.69 0.95) 0.01* 4.53 5.25 0.84 (0.72 0.98) 0.03* 4.47 5.25 0.83 (0.72 0.95) 0.005* 1.61 1.94 0.82 (0.63 1.07) 0.14* 1.47 1.94 0.75 (0.57 0.98) 0.03* 1.54 1.94 0.78 (0.62 0.98) 0.03* 0.4 0.6 0.8 1 1.25 1.67 Ticagrelor better Placebo better Ticagrelor 90 mg bid Ticagrelor 60 mg bid Ticagrelor pooled *Indicates nominal P value; P<0.026 indicates statistical significance Bonaca MP et al. N Engl J Med 2015;372:1791 1800 22
PEGASUS-TIMI 54: Bleeding 5 3-year KM event rate 4 3 2 1 0 P<0.001 2.6 2.3 1.1 TIMI major bleeding Ticagrelor 90 mg bid Ticagrelor 60 mg bid Placebo P<0.001 P=NS P=NS P=NS 1.3 1.2 0.4 0.6 0.7 0.6 0.6 0.6 0.5 0.3 0.3 0.1 TIMI minor bleedingfatal bleeding or ICH Fatal bleeding ICH Rates are presented as 3-year Kaplan-Meier estimates Bonaca MP et al. N Engl J Med 2015;372:1791 1800 23
PEGASUS-TIMI 54: Safety Endpoints Endpoint Ticagrelor 90 mg bid N=6988; n (%) Ticagrelor 60 mg bid N=6958; n (%) Placebo N=6996; n (%) Ticagrelor 90 mg bid vs placebo HR (95% CI) Ticagrelor 60 mg bid vs placebo HR (95% CI) Secondary safety endpoints TIMI minor bleeding 66 (1.31) 55 (1.18) 18 (0.36) 4.15 (2.47 7.00) P<0.001 3.31 (1.94 5.63) P<0.001 Bleeding requiring transfusion Bleeding leading to study drug discontinuation 122 (2.43) 105 (2.09) 37 (0.72) 3.75 (2.59 5.42) P<0.001 453 (7.81) 354 (6.15) 86 (1.50) 5.79 (4.60 7.29) P<0.001 3.08 (2.12 4.48) P<0.001 4.40 (3.48 5.57) P<0.001 Rates are presented as 3-year Kaplan-Meier estimates n = number of patients with events, not the number of events Bonaca MP et al. N Engl J Med 2015;372:1791 1800 24
PEGASUS withdrawal: reduction in MACE
PEGASUS-TIMI 54: Conclusions PEGASUS-TIMI 54 is the first prospective, randomized, controlled clinical trial appropriately powered to assess the benefit of long-term DAPT in patients with prior MI The study therefore suggests that prolonged antiplatelet therapy with ticagrelor plus low-dose ASA may represent a new strategy to reduce atherothrombotic events in appropriately selected patients with prior MI 1. Bhatt DL et al. JAMA 2010;304:1350 1357 2. Fox KA et al. Eur Heart J 2010;31:2755 2764 3. Jernberg T et al. Eur Heart J 2015; pii: ehu505. [Epub ahead of print] 26
Short term vs 12 month 12 month vs extended Cardiov. mortality Stent thrombosis (definite,late,ve ry late) MI Major bleeding Non cardio mortality
2015 ESC Guidelines on NSTE-ACS
2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease
Διάρκεια διπλής αντιαιµοπεταλιακής αγωγής µετά από οξύ στεφανιαίο σύνδροµο Economics Θα συµορφωθει ο ασθενης?
ΣΥΜΠΕΡΑΣΜΑΤΑ Θα πρεπει να λαβουµε υπ οψιν στον ασθενη µας τον κινδυνο ισχαιµιας και αιµορραγιας Το ειδος του stent Ποσο καλα ανεχτηκε τη διπλη θεραπεια Για να αποφασισουµε ποσο θα παρατεινουµε τη διπλη θεραπεια ΕΞΑΤΟΜΙΚΕΥΣΗ ΘΕΡΑΠΕΙΑΣ