Dual Antiplatelet Therapy: Time for a Paradigm Shift? 5 years after PLATO Experience from the Daily Clinical Practice Hans Rickli
Goals with antithrombotic treatment Acute coronary syndrome Risk reduction of cardiovascular events Myocardial infarction Death Stroke Risk reduction of stent thrombosis Prehospital treatment to achieve rapid and effective platelet inhibition and anticoagulation Minimizing the risk of bleeding 18.06.2015
Complications and outcome in STEMI patients (N=27 207) Reduction of time delays Better risk stratification Invasive approach Antithrombotic therapy *developing during hospitalization
Reperfusion therapy in STEMI patients (N=27 207) P<0.001
P2Y12 inhibitors at discharge in ACS patients (N=12,278)
Clopidogrel across spectrum of CAD
Biotransformation Mode of ActionClopidogrel, Prasugrel und Ticagrelor Schomig AS. Ticagrelor Is There Need for a New Player in the Antiplatelet-Therapy Field? New Eng J Med 2009; 361(11): 1108-1111
Antiplatelet therapy: efficacy vs. safety or Ticagrelor Cuisset; Euro PCR 2010, Paris
5 years after PLATO: Antiplatelet therapy in NSTEMI Guidelines ESC Guidelines for the management of acutecoronary syndromes in patients presenting without persistent ST-segment elevation; Europ Heart J 2011
18.06.2015 Antiplatelet therapy in patients with (STEMI 2012)
For medical use only may contain off lable topics 5 years after PLATO: ESC guidelines 2014 myocardial revascularization NSTE-ACS undergoing PCI STEMI undergoing PCI Windecker et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619
Guidelines are usefull but don t stop thinking
Important points to consider: Prasugrel Ticagrelor Study design PCI study All-Comers -study invasive invasive or conservative conservative 0 % 28 % Revascularization strategy: PCI PCI or CABG CABG: 1 % 10 % of the study group and 14% of the invasive gr. PCI: 99 % 62 % STEMI: 26 % 38 % Loading with Clopidogrel: Relatively late 300 mg early 300-600 mg Triton-TIMI 38: New Engl J Med 2007;357:2001-2015 Plato: N Engl J Med 2009;361:1045-57
Primary endpoint: Ticagrelor 0,5 1,0 1,5 Risk reduction as compared to Clopidogrel Risk increase as compared Clopidogrel Triton-TIMI 38: New Engl J Med 2007;357:2001 Plato: N Engl J Med 2009;361:1045-57
Conservative management: Total mortality Prasugrel Clopidogrel --- --- Trilogy ACS Without benefit as compared to Clopidogrel in TRITON no conservative group! Ticagrelor 6,1 % (signifikant) Clopidogrel 8,2 % in PLATO: n = 5216 = 28% 0,5 1,0 1,5 Risk reduction as compared to Clopidogrel Risk increase as compared Clopidogrel
Major bleedings: ( TIMI major ) without CABG-Patients Prasugrel 2,4 % (significant) Clopidogrel 1,8 % Ticagrelor 2,8 % (significant) Clopidogrel 2,2 % 0,5 1,0 1,5 Risk reduction as compared to Clopidogrel Risk increase as compared Clopidogrel
PLATO Trial PLATO CABG substudy Primary endpoint (MACCE) 11.7% Overall mortality 9.7% 9.8% 4.7% Major bleeding Major bleeding 11.6% 11.2% Wallentin L et al. NEJM 2009;361:1045-57. Held C et al. JACC 2011;57:672-84.
trial stopped early when a planned interim analysis showed that pretreatment was associated with an increased risk of major bleeding 7d: (2.6% vs. 1.4%, p=0.006) 30 days (2.9% vs. 1.5%, p=0.002)
Clopidogrel vs Prasugrel/Ticagrelor Key messages Prasugrel and Ticagrelor: net clinical benefit over Clopidogrel in ACS patients Ticagrelor evaluated in allcomers study (PLATO) Benefit through all subgroups CABG/Conservative tx No restriction in elderly (>75yrs), weight < 60kg and history of TIA/Stroke Prasugrel in PCI study (TRITON) Good results in STEMI pts, diabetic population No benefit in patients with conservative management (Trilogy ACS) Elevated bleeding risk with pretreatment (Accoast) not recommended, if history of Stroke - dose reduction if age > 75 yrs, weight < 60kg)
Major adverse CV events up to 30 days
Definite stent thrombosis up to 10 days
Definite stent thrombosis up to 30 days
Conclusion Pre-hospital ticagrelor administration a short time before PCI in patients with ongoing STEMI is safe but does not improve pre-pci coronary reperfusion. It may, however, reduce the risk of post-pci stent thrombosis.
Windecker et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619
Keep it simple in network treatment 5000 Heparin i.v. Ticagrelor (Brillique ) Loading Dose 2x90 mg/d Triage im Spital/PCI-Zentrum
5 years after PLATO: What else? Rivaroxaban Apixaban Edoxaben Cangrelor Dabigatran
5 years after PLATO: What else? Different Clinical conditions ACS NSTEMI conservative NSTEMI/STEMI with PCI/CABG Important co-factors to consider Triple therapy for newer drugs not approved Impact of Age, Diabetes, other comorbidity. Stable CAD with Stents RCTs with Ticagrelor or Prasugrel lacking
Trends in triple antithrombotic therapy at discharge in ACS patients with atrial fibrillation at admission (n=294) Increasing rate of Combination of newer P2Y12 inhibitors together with OAC - In hospital bleeding, in hospitaloutcome, at 1 yr? Increasing rate of triple tx with NOACs Unpublished data
5 years after PLATO: What else?
5 years after PLATO Experience from the Daily Clinical Practice Risk reduction of cardiovascular events remains still a goal (balance between thrombotic and bleeding risk) newer antithrombotics are integrated in daily practice in ACS Management of ACS patients in regional networks: need of simple and clear strategy In contrast to the guidelines a substantial number of ACS patients is treated with Prasugrel or Ticagrelor in combination with anticoagulation (VKA or NOACs) 18.06.2015
Thank you!
L.CH.HC.11.2011.0079-EN 18.06.2015
Fallbeispiel 1a 71-jährige Patientin Bekannte Koronare und hypertensive Herzkrankheit St. n. inferiorem Myokardinfarkt vor Jahren (Stent) Beschwerdefrei (keine Angina) und ordentlich belastbar Medikation: Bisoprolol (Concor ) Ramipril (Triatec ) Atorvastatin (Sortis ) Aspirin Colon-Carcinom: Hemikolektomie links
Gerstein NS, et al. Anesth Analg 2015; 120: 5670-5
Kardiovaskuläres Manual KSSG 2015
ONSET/OFFSET Studie * P<0.05, ** P<0.001, *** P<0.0001 Ticagrelor vs. Clopidogrel Ticagrelor 180-mg Initialdosis in stabilen KHK-Patienten Clopidogrel 600-mg Initialdosis in stabilen KHK-Patienten Gurbel PA et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577 2585