Ivan Anderson, MDRIHVH Cardiology

Antiplatelet and Anti-Thrombotic

Therapy

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-platelet

therapy (the triple threat)

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-platelet

therapy (the triple threat)

https://www.chadsvasc.org

Dosing

Treatment Doses Deep Venous Thrombosis and Pulmonary Embolism

• Pradaxa: 150 mg PO BID (same)• Xarelto: 15 mg PO BID x 21 days

– Then as per previous slide

• Eliquis: 10 mg PO BID x 7 days– Then as per previous slide

Europace (2013) 15, 625–651

Take Xarelto with food

RELY Data (Pradaxa vs Warfarin)

ROCKET-AF Data (Xarelto vs Warfarin)

ARISTOTLE Data (Eliquis vs Warfarin)

Package Insert Apixaban – Now Removed

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-platelet

therapy (the triple threat)

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-platelet

therapy (the triple threat)

Acute Coronary Syndromes.

Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

An Activated Platelet

Platelet Activation

Central Role of P2Y12 Receptor in Thrombus Propogation

J Clin Invest. 2004 Feb 1; 113(3): 340–345

Schömig A. N Engl J Med 2009;361:1108-1111.

Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and Ticagrelor.

Summary of Recommendations for Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS and PCI.

Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

Summary of Recommendations for Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or

Likely NSTE-ACS and PCI.

• Addition of Plavix or Ticagrelor is Class 1 Level of Evidence B for early care of Non-ST Elevation Acute Coronary Syndrome

Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. N Engl J Med 2001;345:494-502.

Cumulative Hazard Rates for the First Primary Outcome (Death from Cardiovascular Causes, Nonfatal Myocardial Infarction, or Stroke) during the 12

Months of the Study.

~600% Increased Risk of Stent Thrombosis Stopping DAPT after BMS

Circulation. 2007;115:813-818 (DAPT = Dual Anti-Platelet Therapy, BMS – Bare Metal Stent)

Am J Cardiol 2006;98:352–356

Stent Related Risk Factors for InstentThrombosis

• Bifurcation stenting• Eccentric stenosis• Long stents (e.g. 26 or 30 mm)• Tortuous artery

STEMI After Premature Discontinuation of Anti-Platelet Therapy

JACC Vol. 35, No. 5, 2000

A Few Notes on Effient (prasugrel) and Brilinta (ticagrelor)

• Effient (prasugrel): black box warning – do not use if prior stroke

• Brilinta (ticagrelor)– Often may cause dyspnea– Can lead to bradyarrhythmias

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-platelet

therapy (the triple threat)

Outline

• Anti-thrombotic therapy– Risk stratification of stroke with atrial fibrillation– DVT and PE treatment– Pharmacology

• Anti-platelet therapy– Pharmacology of PGY-12 antagonists– Risk of premature discontinuation of dual anti-platelet

therapy• Combination of anti-thrombotic and anti-

platelet therapy (the triple threat)

WOEST Trial

• Randomized control trial of double versus triple therapy after PCI– Double therapy: Plavix + Coumadin– Triple therapy: Aspirin + Plavix + Coumadin

• Primary Endpoint: any bleeding

Lancet 2013; 381: 1107–15

WOEST Trial (Death and Stent Thrombosis)

Lancet 2013; 381: 1107–15

PIONEER AF-PCI Trial

• Randomized control trial of anti-coagulation strategies with non-valvular A fib

• 2124 Patients randomized 1:1:1 to 3 groups– Group 1: Xarelto 15 mg + P2Y12 inhibitor x 12 mo– Group 2: Xarelto 2.5 mg + DAPT for 1, 6 or 12 mo– Group 3: Coumadin + DAPT for 1, 6 or 12 mo

(DAPT = Dual Anti-Platelet Therapy)

Gibson CM et al. N Engl J Med 2016;375:2423-2434.

Gibson CM et al. N Engl J Med 2016;375:2423-2434.

Stratification, Randomization, and Follow-up.

Gibson CM et al. N Engl J Med 2016;375:2423-2434.

Cumulative Incidence of the Primary Safety End Point and a Secondary Efficacy End Point.

10 Endpoint: Bleeding

2nd Endpoint: Cardiovascular Death, MI, CVA

Group 1: Xarelto 15 mg + P2Y12 inhibitor x 12 mo

Group 2: Xarelto 2.5 mg + DAPT for 1, 6 or 12 mo

Group 3: Coumadin + DAPT for 1, 6 or 12 mo

Questions

Eikelboom JW et al. N Engl J Med 2017;377:1319-1330.

Cumulative Incidence of the Primary Efficacy Outcome among Participants Receiving Rivaroxaban plus Aspirin, Rivaroxaban

Alone, or Aspirin Alone.