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Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd
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Pharmacology what's new_in_anticoagulation_medications-james_grocepharmd

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  • 1. Pharmacology – What’s New in Anticoagulation Medications James B. Groce III, PharmD, CACP Professor Campbell University College of Pharmacy and Health Sciences Clinical Assistant Professor of Medicine, UNC Clinical Pharmacy Specialist-Anticoagulation Cone Health, Greensboro, NC
  • 2. Faculty Disclosure • The speaker reported the following financial relationships or relationships to products or devices he or his spouse has with commercial interests related to the content of this CME activity: – James B. Groce III, PharmD, CACP • Fees for non-CME services received directly from a commercial interest or their agents: • Boehringer Ingelheim Pharmaceuticals, Inc., • Bristol-Myers Squibb • Eisai Pharmaceuticals, Inc. • Janssen Pharmaceuticals, Inc. • Sanofi-aventis • Stago-Diagnostica • The Joint Commission
  • 3. Objectives • Review the cardiology focused indications of the new anticoagulant medications. • Discuss the benefits and shortcomings of the new anticoagulant medications—compared to the traditional comparator. • Identify key opportunities in the management of patients using the new anticoagulants.
  • 4. Atrial Fibrillation and Anticoagulation • An estimated 2.6 million Americans have AF – Prevalence of AF is increasing—estimated to be 12 million patients by 2050 • AF is responsible for 15-20% of all strokes – Untreated stroke risk with AF is approximately 5% – AF strokes are severe: causing death and disability • Anticoagulation therapy – Effectively lowers the incidence and severity of AF stroke • Fewer than 60% of eligible patients with AF have received anticoagulation with warfarin – Many patients with AF have INRs below the recommended therapeutic range Ogilvie IM, et al. Am J Med. 2010;123:638-645. Hylek E et al. N Engl J Med. 2003; 349:1019-1026. AF=atrial fibrillation. INR=international normalized ratio.
  • 5. ACCF/AHA/HRS Focus Update 2011 Guidelines for Antithrombotic Therapy to Prevent Stroke Risk Category Recommended Therapy No risk factors aspirin, 81-325 mg daily One moderate-risk factor (Age ≥75 yrs, HTN, CHF, LVEF ≤35%, and diabetes) aspirin, 81-325 mg daily, or warfarin (INR 2.0-3.0, target 2.5), or dabigatran† Any high-risk factor or more than 1 moderate-risk factor (Previous stroke, TIA or embolism, mitral stenosis, and Prosthetic heart valve*) warfarin (INR 2.0 to 3.0, target 2.5),* or dabigatran † *If mechanical valve, target INR >2.5. † dabigatran is useful as an alternative to warfarin in patients with AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure, or advanced liver disease. HTN=hypertension. INR=international normalized ratio. CHF=congestive heart failure. Fuster V, et al. J Am Coll Cardiol. 2006;48:e149-e246. LVEF=left ventricular ejection fraction. Wann SL, et al. Heart Rhythm. 2011;8:e1-e8.
  • 6. Therapies to Prevent Thrombotic Stroke Anticoagulants Vitamin K Antagonist Antiplatelet Agents New Anticoagulants aspirin +/- clopidogrel Non-antithrombotic Drugs Antihypertensive Statin Left Atrial Appendage Occlusion or Excision warfarin Non-warfarin Vitamin K Antagonists • tecarfarin Direct Thrombin Inhibitors • ximelagatran • dabigatran • AZD 0837 Factor Xa Inhibitors • apixaban • rivaroxaban • idraparinux • edoxaban • YM150 • betrixaban • LY517717 • Umbrella device • External clip • Surgical excision Antiarrhythmic
  • 7. Characteristics of an Ideal Anticoagulant High efficacy-tosafety index Parenteral and oral administration Minimal non-anticoagulant side effects Hirsh J et al. Blood. 2005;105(2):453-461. Predictable dose response (no need for monitoring) Rapid onset of action Antidote Minimal drug-drug interactions
  • 8. Newer Oral Anticoagulants dabigatran1,4* rivaroxaban2 apixaban3 Manufacturer Boehringer Ingelheim Bayer with Ortho-McNeil Bristol-Myers Squibb with Pfizer Brand Name Pradaxa® Xarelto® Eliquis® •Approved in U.S. 2010 • Approved in U.S. 2011 • Approved in the EU 2011 Approval Status Indication Dosage Recommendation Mechanism of Action 1. 2. •Stroke prevention in patients with AF • Thromboembolism in adult patients undergoing elective hip or knee replacement surgery • Stroke prevention in patients with AF • Not approved in US • EU indication: Prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery 150mg bid (Clcr > 30mL/min) 75mg bid (Clcr 15 – 30mL/min) 75mg bid (Clcr 30 – 50mL/min)* 10mg qd Ortho 20mg qd Afib Clcr > 50mL/min 15mg qd Afib (Clcr 15-50mL/min) 5 mg bid Direct factor IIa inhibitor Direct factor Xa inhibitor Direct factor Xa inhibitor dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2011. rivaroxaban prescribing information. Janssen Pharmaceuticals, Inc. 2011. 3. 4. apixaban European Union summary of product characteristics. Pfizer and Bristol-Myers Squibb. 2011. *dronedarone, systemic ketoconazole
  • 9. Pharmacokinetic Properties of the New Oral Anticoagulants dabigatran T1/2 Metabolism rivaroxaban apixaban 12-14 hours 5-9 hours 8-15 hours Conjugation (esterase Oxidation (mainly 70% unchanged catalyzed hydrolysis via CYP3A4) and 30% Inactive in liver or plasma) hydrolysis metabolites Renal Excretion 80% 36% 30% Substrate for p-glycoprotein Yes Yes Yes Metabolized by CYP3A4 No Yes Yes Wittkowsky AK. J Thromb Thrombolysis. 2010;29:182-191. Ufer M. Thrombosis and Haemostasis. 2010;103:572-585.
  • 10. Differences Between New Oral Anticoagulants and Warfarin Parameter Oral Anticoagulants Warfarin Onset/Offset of action Rapid Slow Dose–anticoagulant effect relationship Linear Predictable Low probability of interaction Moderate probability of interaction Not required Not available Required POCT and PST Available Food–drug interactions Monitoring for anticoagulant effect POCT=point-of-care testing PST=patient self-testing
  • 11. AF Stroke Risk
  • 12. Stroke Risk Stratification in AF CHADS2 Risk Factor Cardiac Failure HTN Age ≥75 y Diabetes Stroke Total Score 0 1 2 3 4 5 6 7 8 9 Score 1 1 1 1 2 Annual Risk of Stroke (%) 1.9 0 2.8 1.3 4.0 2.2 3.2 CHA2DS2-VASc CHADS2 5.9 8.5 4.0 12.5 6.7 18.2 9.8 9.6 6.7 15.2 Lip GY, Halperin JL. Am J Med. 2010;123(6):484-488. Camm AJ, et al. Eur Heart J. 2010;31(19):2369-2429. CHA2DS2-VASc Risk Factor Score Cardiac Failure 1 HTN 1 Age ≥75 y 2 Diabetes 1 Stroke 2 Vascular Disease (MI, PAD, 1 Aortic Atherosclerosis) Age 65-74 y 1 Sex Category (Female) 1 HTN=hypertension. MI=myocardial infarction. PAD=peripheral artery disease.
  • 13. RE-LY: Study Design Atrial fibrillation ≥1 Risk Factor Absence of contra-indications 951 centers in 44 countries 10 efficacy outcome=stroke or systemic embolism 10 safety outcome=major bleeding Non-inferiority margin=1.46 R Open warfarin (INR 2.0-3.0) n=6000 • • • • Performed December 2005-March 2009 Median follow-up: 2.0 years Follow-up 99.9% complete Mean TTR=64% (patients on warfarin) Blinded dabigatran etexilate 110 mg bid n=6000 bid=twice daily. INR=international normalized ratio. RE-LY=Randomized Evaluation of Long-Term Anticoagulation Therapy. Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151. dabigatran etexilate 150 mg bid n=6000
  • 14. RE-LY Trial: Primary Efficacy & Safety Outcomes Safety Outcomes Efficacy Outcomes dabigatran 150 mg better warfarin better Stroke/systemic embolism1 0.65 (0.52-0.81) 0.90 (0.74-1.10) Myocardial Infarction1 1.27 (0.94-1.71) 1.29 (0.96-1.75) Vascular death1 0.85 (0.72-0.99) 0.90 (0.77-1.06) Intracranial Hemorrhage (ICH)1 0.41 (0.28-0.60) 0.30 (0.19-0.45) Major GI bleeding2 1.47 (1.17-1.84) 1.06 (0.83-1.35) Major bleeding1 0.93 (0.81-1.07) Total bleeding1 0.91 (0.85-0.96) 0.80 (0.70-0.93) 0.78 (0.73-0.83) 0.0 0.5 1.0 1.5 2.0 Relative risk 1. dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. March 2011. 2. Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151. RE-LY=Randomized Evaluation of Long-term Anticoagulation Therapy.
  • 15. ROCKET AF Study Design NVAF Randomized double-blind/ double-dummy (N=14,264) rivaroxaban 20 mg/d (15 mg/d for CrCl 30 to <50 mL/min) CHADS2 Risk Factors • Prior stroke, TIA, or non-CNS systemic embolus – OR – At least 2 required • CHF or LVEF ≤35% • Hypertension • Age ≥75 years • Diabetes warfarin INR target: 2.0 to 3.0 inclusive Monthly assessments* warfarin management was determined by clinician  Enrollment of subjects without prior stroke, TIA, or systemic embolism and only 2 factors capped at 10% Abbreviations: CHADS2 = congestive heart failure, hypertension, age, diabetes, prior stroke or TIA; CHF = congestive heart failure; CrCl = creatinine clearance; INR = international normalized ratio. *Patients seen at weeks 1, 2, and 4, then as clinically indicated but at least monthly thereafter. 1. Patel MR et al. N Engl J Med. 2011;365(10):883-891. 2. ROCKET AF Study Investigators. Am Heart J. 2010;159(3):340-347. 15
  • 16. Cumulative Event Rate (%) Rocket-AF Primary Efficacy Outcome Stroke and Non–CNS Embolism 6 rivaroxaban 5 warfarin 2.12 2.42 Rate/100 PTY 4 3 rivaroxaban warfarin 2 HR (95% CI): 0.88 (0.74-1.03) Noninferiority P value <.001 1 0 0 120 240 360 480 600 720 840 960 1080 Days From Randomization No. at risk Rivaroxaban 7081 6879 6683 6470 5264 4105 2951 1785 768 155 Warfarin 6656 6440 5225 4087 2944 1783 776 154 7090 6871 *Included all randomized subjects followed for events both on and off study drug until end of study site notification (N=14171). Patel MR et al. N Engl J Med. 2011;365(10):883-891.
  • 17. Rocket-AF Primary Safety Outcomes Events, No. (Rate/100 PTY) rivaroxaban (n=7061)* warfarin (n=7082)* HR (95% CI) P value 395 (3.60) 386 (3.45) 1.04 (0.90-1.20) .576 Bleeding causing death 27 (0.24) 55 (0.48) 0.50 (0.31-0.79) .003 Critical organ bleeding† 91 (0.82) 133 (1.18) 0.69 (0.53-0.91) .007 Hgb drop ≥2 g/dL 305 (2.77) 254 (2.26) 1.22 (1.03-1.44) .019 Transfusion (>2 units) 183 (1.65) 149 (1.32) 1.25 (1.01-1.55) .044 55 (0.49) 84 (0.74) 0.67 (0.47-0.94) .019 --- .001 Major bleeding (any) Bleeding site Intracranial hemorrhage‡ GI bleeding§ 224 (---) 154 (---) Abbreviations: GI, gastrointestinal; hgb, hemoglobin. *Safety population on-treatment. †Critical bleeding sites included intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome or retroperitoneal. ‡Intracranial hemorrhage included intraparenchymal, intraventricular, subarachnoid, subdural hematoma, and epidural hematoma. §GI hemorrhage included upper GI, lower GI, and rectal bleeds. Patel MR et al. N Engl J Med. 2011;365(10):883-891.
  • 18. ARISTOTLE: Study Design Inclusion risk factors  Age ≥ 75 years  Prior stroke, TIA or SE  HF or LVEF ≤ 40%  Diabetes mellitus  Hypertension Randomize double blind, double dummy (n = 18,201) Exclusion  Mechanical prosthetic valve  Severe renal insufficiency  Need for aspirin plus thienopyridine apixaban 5 mg oral twice daily warfarin (2.5 mg BID in selected patients) (target INR 2-3) warfarin/warfarin placebo adjusted by INR/sham INR based on encrypted point-of-care testing device Primary outcome: stroke or systemic embolism Granger CB, et al. N Engl J Med. 2011 [Aug 28]. ePub ahead of print. doi: 10.1056/NEJMoa1107039.
  • 19. ARISTOTLE Main Trial Results Stroke or systemic embolism ISTH major bleeding 21% RRR apixaban 212 patients, 1.27% per year warfarin 265 patients, 1.60% per year HR 0.79 (95% CI, 0.66–0.95); P=0.011 31% RRR apixaban 327 patients, 2.13% per year warfarin 462 patients, 3.09% per year HR 0.69 (95% CI, 0.60–0.80); P<0.001 Median TTR 66% Granger CB, et al. N Engl J Med. 2011 [Aug 28]. ePub ahead of print. doi: 10.1056/NEJMoa1107039.
  • 20. What Is the Impact of Time in Target Range (TTR)?
  • 21. Time in Target Range (TTR) • What is the TTR for the patient below?
  • 22. 3 Methods for Calculating TTR: Percentage of Visits in Range • For an individual patient, the number of visits “in range” is divided by the number of visits 3 Patient Visits with INR in range = 5 Total Patient Visits 60% TTR
  • 23. 3 Methods for Calculating TTR: Cross Section of Patients In Range • For a group of patients, a date is selected and all patients are evaluated on the last reading prior to that date. Sept 30, 2011 is selected to assess TTR for 100 patients • Patients are evaluated using last INR readings prior to Sept 30, 2011 • Out of 100 patients, 71 had readings in therapeutic range 71 Patient with INR in range = 100 Total Patients 71% TTR As of Sept 30, 2011
  • 24. 3 Methods for Calculating TTR: % Days in Range (Rosendaal Method) More complicated methodology which looks at the amount of time between visits to determine how long the patient might have been within their therapeutic range – Between measurements on May 1 and May 31, it is assumed that the patient slowly moved from 2.5 to 3.5 over 30 days – On May 15th, the patient was probably over 3.0 INR Level • 4 3.5 3 2.5 2 1.5 1 0.5 0 3.5 2.8 2.5 15 days 15 days In range Out of range Apr 29, 2011 May 1, 2011 Patient was in range 50% of the time May 31, 2011
  • 25. Phase 3 Trials in Atrial Fibrillation: TTR and warfarin Efficacy Mean TTR (%) Mean CHADS2 Score CHADS2 ≥3 Patients (%) ROCKET AF1 55 3.5 RE-LY2 64 ARISTOTLE3 62 Study Primary Efficacy Rate (warfarin Arm)* Overall CHADS2 2 CHADS2 ≥3 87.0 2.2 1.3 2.3 2.1 32.5 1.7 1.4 2.7 2.1 30.2 1.6 1.4 2.8 ♦ ROCKET AF enrolled a population of patients with AF at higher risk of stroke ♦ The overall event rate for the warfarin arm in ROCKET AF was higher than those reported in RE-LY and ARISTOTLE ♦ This difference may have been driven by the greater proportion of CHADS2 ≥3 patients enrolled in ROCKET AF/ *Rate per 100 patient-years. 1. Patel MR et al. N Engl J Med. 2011;365(10):883-891 2. Connolly SJ, et al. N Engl J Med. 2009;361:1139-51. doi: 10.1056/NEJMoa0905561. 3. Granger CB, et al. N Engl J Med. 2011 [Aug 28]. ePub ahead of print. doi: 10.1056/NEJMoa1107039.
  • 26. Benefits and shortcomings of the new anticoagulant medications—compared to the traditional comparator.
  • 27. Benefits and shortcomings of the currently available anticoagulant therapies. • New oral anticoagulants – No coagulation testing • Less time and travel • No finger stick or venipuncture – Fixed dose: no dose finding – Primary Care or Cardiology • Simplifies responsibility – Fewer strengths • Possible decease in dosing errors – Diet • Less effect
  • 28. Benefits and shortcomings of the currently available anticoagulant therapies. • Given the challenges associated with warfarin, an oral anticoagulant is especially attractive • Features of oral anticoagulants that may be associated with greater adherence include – Do not require monitoring – Fewer adverse effects, drug-drug, and drug-food interactions • Improved adherence may reduce the risk of subtherapeutic INR and may lead to better treatment outcomes and possibly lower costs Kirsch B. Manag Care. 2011;20(2):33-36.
  • 29. Identify key opportunities in the management of patients using the new anticoagulants
  • 30. Key opportunities in the management of patients • • • • Review appropriateness prior to dispensing CBC q72h while inpatient Recommend CBC 7-10 days post discharge Discharge counseling CBC=complete blood count. Moses Cone Health System Pharmacy & Therapeutics Formulary Review. January 2011. Approved.
  • 31. Key opportunities in the management of patients Creatinine Clearance Recommended Dose of Dabigatran >30 mL/min 150 mg twice daily* 15 – 30 mL/min 30 – 50 mL/min 75 mg twice daily† 75mg twice daily‡ <15 mL/min Dosing recommendations cannot be provided * With or without food. † Based upon pharmacokinetic modeling, estimated exposure to dabigatran increases with the severity of renal function impairment. ‡For patients on P-gp inhibitors (dronedarone or systemic ketoconazole) dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2011.
  • 32. Key opportunities in the management of patients • Converting from warfarin to dabigatran – Discontinue warfarin – Start with dabigatran when INR <2.0 • Converting from dabigatran to warfarin Creatinine Clearance Recommended Starting Time of Warfarin >50 mL/min 3 days before discontinuing dabigatran 31-50 mL/min 2 days before discontinuing dabigatran 15-30 mL/min 1 day before discontinuing dabigatran <15 mL/min No recommendations can be made INR=international normalized ratio. dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2011.
  • 33. Key opportunities in the management of patients Administration of Parenteral Anticoagulant Recommended Starting Time of Dabigatran Intermittent dosing 0-2 hours before time of next dose Continuous infusion At time of discontinuation dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2011.
  • 34. Key opportunities in the management of patients Creatinine Clearance Recommended Starting Time of Parenteral Anticoagulant CrCl ≥30 mL/min 12 hours after last dose of dabigatran CrCl ≤30 mL/min 24 hours after last dose of dabigatran CrCl=creatinine clearance. dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2011.
  • 35. Key opportunities in the management of patients warfarin rivaroxaban rivaroxaban  warfarin ♦ There are no clinical trial data Discontinue warfarin Initiate rivaroxaban when the INR is below 3.0 to avoid inadequate anticoagulation to guide converting from rivaroxaban to warfarin ♦ Rivaroxaban may affect INR, so INR measurements made during coadministration of rivaroxaban with warfarin may not be useful ♦ One approach is to discontnue rivaroxaban and begin both a parenteral anticoagulant and warfarin when the next rivaroxaban dose would have been taken* *The recommendation to use a parenteral anticoagulant together with warfarin after discontinuing rivaroxaban is analogous to the bridging protocol recommended for starting moderate- to high-risk patients on warfarin.1 Fuster V et al. J Am Coll Cardiol. 2011;57(11):e101-e198.
  • 36. • • • Anticoagulation after discontinuation was not stipulated in ROCKET AF Warfarin patients who completed the study were generally maintained on warfarin Rivaroxaban patients were generally switched to warfarin – There was no coadministration of warfarin and rivaroxaban – This resulted in inadequate anticoagulation after stopping rivaroxaban until attaining a therapeutic INR Patel MR et al. N Engl J Med. 2011;365(10):883-891. No. of Strokes Key opportunities in the management of patients rivaroxaban (n=4637) warfarin (n=4691)
  • 37. Key opportunities in the management of patients • Short half-life of oral anticoagulants makes adherence important • Reduced monitoring may deny the physician the opportunity for patient education and the earlier detection of problems – Denies the practitioner the opportunity to tailor the intensity of anticoagulant therapy for patient-specific factors • Acquisition costs associated with oral anticoagulants will be greater than for warfarin – Payers may erect barriers to access – Cost-sharing may decrease adherence Ansell J. Hematology. 2010;221-228.
  • 38. Key opportunities in the management of patients • Protocol development for use and management – Short half-life of oral anticoagulants makes adherence important • Protocol development for use and management of life-threatening/catastrophic bleed(s) – No validated tests to measure anticoagulation effect – No antidote for most agents – Assessment of compliance more difficult than with vitamin K antagonists Sobieraj-Teague M, et al. Semin Thromb Hemost. 2009;35:515-524.
  • 39. Key opportunities in the management of patients • The successful use of (anticoagulation) depends on an “essential triad” which includes a – Vigilant clinician – Cooperative (well educated) patient – Readily available and reliable laboratory • If these factors are present, continuous use of anticoagulation is practical...and effective; if not, the use of the drug is dangerous… Foley WT, Wright IS. Am J Med Sci. 1949;217:136-144. Aske JM, Cherry CB. J Am Med Assoc. 1950;144:97-100.
  • 40. Key opportunities in the management of patients • Availability of new oral anticoagulants will impact the way we think about care delivery and management for patients with atrial fibrillation – We must STOP focusing upon INRs—and instead, as practitioners—focus upon assuring: • The impact these new drugs have upon reduction of stroke and intracranial hemorrhage! • Compliance, patient education—regarding their disease state as well as their drug therapies • Continuing to deliver a “systematic means of oversight” for drug therapies and disease states—for which at their extremes— patients may either bleed to death—or clot to death: – Baseline and periodic assessment of renal function – Evaluation of drug-drug/drug-disease interactions
  • 41. Key opportunities in the management of patients • Anticoagulation therapy lowers the incidence and severity of AF stroke • Less than 60% of eligible AF patients have received anticoagulation therapy • Newer oral anticoagulants exhibit a rapid onset of action, linear kinetics, low probability of drug and food interactions, and do not require monitoring—and, relative to warfarin—have further reduced the liklihood of stroke in the setting of non-valvular atrial fibrillation
  • 42. Summary • Current cardiology indications of the new anticoagulant medications include prevention of stroke in setting of NVAF. • Benefits and shortcomings – New oral agents eliminate a requirement of traditional monitoring and reduce stroke—when compared to warfarin— but lack a means of reversal • Key opportunities for practitioner involvement in the management of patients: – Will remain: provision of a systematic means of oversight • Appropriateness of drug relative to the approved indication(s) • Focus upon renal function and Rx-Rx interaction prevention for new agents
  • 43. Pharmacology – What’s New in Anticoagulation Medications James B. Groce III, PharmD, CACP Professor Campbell University College of Pharmacy and Health Sciences Clinical Assistant Professor of Medicine, UNC Clinical Pharmacy Specialist-Anticoagulation Cone Health, Greensboro, NC

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