Vasopressin Vasopressin Epi Epi ASPIRIN ASPIRIN HEPARINS - - PowerPoint PPT Presentation

“ Anticoagulation and the Heart”

• M. Samir Arnaout M.D

Associate Professor of Medicine C di l Di i i Cardiology Division American University of Beirut-Medical Center

PAF PAF Thrombin Thrombin ADP ADP TXA TXA2

ASPIRIN ASPIRIN

Epi Epi

ASPIRIN ASPIRIN

Vasopressin Vasopressin

PLATELET PLATELET

ASPIRIN ASPIRIN HEPARINS HEPARINS

ASPIRIN ASPIRIN

ASPIRIN ASPIRIN CLOPIDOGREL CLOPIDOGREL

ASPIRIN ASPIRIN

ASPIRIN ASPIRIN ASPIRIN ASPIRIN

5HT HT

GP IIb/IIIa GP IIb/IIIa

Thi k f li Thi k f li

Collagen Collagen GP IIb/IIIa GP IIb/IIIa

GP IIb/IIIa GP IIb/IIIa Thickness of line Thickness of line indicates strength indicates strength

• f activator
• f activator

Fibrinogen Fibrinogen

PLATELET PLATELET

Oral Anticoagulant Oral Anticoagulant Oral Anticoagulant Oral Anticoagulant

Clotting Cascade Clotting Cascade Clotting Cascade Clotting Cascade

Vitamin K Vitamin K-Dependent Dependent Vitamin K Vitamin K Dependent Dependent Clotting Factors Clotting Factors

Vitamin K Vitamin K VII VII Synthesis of Synthesis of Functional Functional Coagulation Coagulation VII VII IX IX X Coagulation Coagulation Factors Factors X II II

Warfarin Mechanism of Warfarin Mechanism of Warfarin Mechanism of Warfarin Mechanism of Action Action

Vitamin K Vitamin K Antagonism VII VII Synthesis of Synthesis of Non Non Functional Functional g

• f

Vitamin K VII VII IX IX X Functional Functional Coagulation Coagulation Factors Factors X II II Warfarin Warfarin

Warfarin: I ndications Warfarin: I ndications Warfarin: I ndications Warfarin: I ndications

Prophylaxis and/or treatment of:

Prophylaxis and/or treatment of:

V th b i d it t i V th b i d it t i – Venous thrombosis and its extension Venous thrombosis and its extension – Pulmonary embolism Pulmonary embolism Th b b li li ti i t d ith AF d Th b b li li ti i t d ith AF d – Thromboembolic complications associated with AF and Thromboembolic complications associated with AF and cardiac valve replacement cardiac valve replacement

P t MI t d th i k f d th t MI P t MI t d th i k f d th t MI

Post MI, to reduce the risk of death, recurrent MI,

Post MI, to reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or and thromboembolic events such as stroke or t i b li ti t i b li ti systemic embolization systemic embolization

Prevention and treatment of cardiac embolism

Prevention and treatment of cardiac embolism

The Fifth American College of Chest Physicians Consensus Conference

Antithrombotic Agents: Antithrombotic Agents: Antithrombotic Agents: Antithrombotic Agents: Mechanism of Action Mechanism of Action

Anticoagulants: prevent clot formation

Anticoagulants: prevent clot formation and extension and extension

Antiplatelet drugs: interfere with

Antiplatelet drugs: interfere with

Antiplatelet drugs: interfere with

Antiplatelet drugs: interfere with platelet activity platelet activity Th b l i di l i i Th b l i di l i i

Thrombolytic agents: dissolve existing

Thrombolytic agents: dissolve existing thrombi thrombi

Prothrombin Time (PT) Prothrombin Time (PT) ( ) ( )

Historically, a most reliable and “relied

Historically, a most reliable and “relied upon” clinical test upon” clinical test

However: However: – Proliferation of thromboplastin reagents with Proliferation of thromboplastin reagents with widely varying sensitivities to reduced levels of widely varying sensitivities to reduced levels of i i K i i K d d l i f h d d l i f h vitamin K vitamin K-dependent clotting factors has dependent clotting factors has

• ccurred
• ccurred

Concept of correct “intensity” of anticoagulant Concept of correct “intensity” of anticoagulant – Concept of correct “intensity” of anticoagulant Concept of correct “intensity” of anticoagulant therapy has changed significantly (low intensity) therapy has changed significantly (low intensity) Problem addressed by use of INR (International Problem addressed by use of INR (International – Problem addressed by use of INR (International Problem addressed by use of INR (International Normalized Ratio) Normalized Ratio)

I NR: I nternational I NR: I nternational li d i li d i Normalized Ratio Normalized Ratio

A mathematical “correction” (of the PT ratio) for

A mathematical “correction” (of the PT ratio) for differences in the sensitivity of thromboplastin differences in the sensitivity of thromboplastin differences in the sensitivity of thromboplastin differences in the sensitivity of thromboplastin reagents reagents

Relies upon “reference” thromboplastins with

Relies upon “reference” thromboplastins with Relies upon reference thromboplastins with Relies upon reference thromboplastins with known sensitivity to antithrombotic effects of oral known sensitivity to antithrombotic effects of oral anticoagulants anticoagulants INR i th PT ti ld h bt i d if th INR i th PT ti ld h bt i d if th

INR is the PT ratio one would have obtained if the

INR is the PT ratio one would have obtained if the “reference” thromboplastin had been used “reference” thromboplastin had been used

Allows for comparison of results between labs and

Allows for comparison of results between labs and

Allows for comparison of results between labs and

Allows for comparison of results between labs and standardizes reporting of the prothrombin time standardizes reporting of the prothrombin time

J Clin Path J Clin Path 1985 1985; ; 38 38: :133 133-

• 134

134; WHO Tech Rep Ser. # ; WHO Tech Rep Ser. #687 983 687 983. .

I NR E ti I NR E ti I NR Equation I NR Equation

( )

Patient’s PT in Seconds Patient’s PT in Seconds

ISI ISI

( )

Patient’s PT in Seconds Patient’s PT in Seconds Mean Normal PT in Seconds Mean Normal PT in Seconds INR = INR =

ISI ISI

( )

INR = International Normalized Ratio INR = International Normalized Ratio ISI = International Sensitivity Index

Warfarin: Dosing I nformation Warfarin: Dosing I nformation Warfarin: Dosing I nformation Warfarin: Dosing I nformation

Individualize dose according to patient

Individualize dose according to patient response(as indicated by INR) response(as indicated by INR) response(as indicated by INR) response(as indicated by INR)

Use of large loading dose not

Use of large loading dose not recommended* recommended* recommended* recommended*

– May increase hemorrhagic complications May increase hemorrhagic complications – Does not offer more rapid protection Does not offer more rapid protection

Low initiation doses are recommended for

Low initiation doses are recommended for elderly/frail/liver elderly/frail/liver-

• diseased/malnourished

diseased/malnourished patients patients

*Harrison L, et al. Ann Intern Med Harrison L, et al. Ann Intern Med 1997 1997; ;126 126: :133 133-

• 136

136.

pat e ts pat e ts

Loading Dose then Loading Dose then Loading Dose then Loading Dose then Maintenance Dose Maintenance Dose

Daily Dose

Maintenance Dose Only Maintenance Dose Only Maintenance Dose Only Maintenance Dose Only

Daily Dose

Maintenance Maintenance Loading Dose then Loading Dose then Maintenance Maintenance Dose Only Dose Only Loading Dose then Loading Dose then Maintenance Dose Maintenance Dose

Daily Dose Daily Dose

Conversion from Heparin Conversion from Heparin Conversion from Heparin Conversion from Heparin to Warfarin to Warfarin

May begin concomitantly with heparin

May begin concomitantly with heparin th th therapy therapy

Heparin should be continued for a minimum

Heparin should be continued for a minimum

• f four days
• f four days

– Time to peak antithrombotic effect of warfarin is Time to peak antithrombotic effect of warfarin is delayed delayed 96 96 hours (despite INR) hours (despite INR)

When INR reaches desired therapeutic

When INR reaches desired therapeutic range, discontinue heparin (after a range, discontinue heparin (after a minimum of four days) minimum of four days)

Relative Contraindications Relative Contraindications Relative Contraindications Relative Contraindications to Warfarin Therapy to Warfarin Therapy

Pregnancy

Pregnancy

Situations where the risk of

Situations where the risk of hemorrhage is greater than the hemorrhage is greater than the hemorrhage is greater than the hemorrhage is greater than the potential clinical benefits of therapy potential clinical benefits of therapy

U t ll d l h l/d b U t ll d l h l/d b – Uncontrolled alcohol/drug abuse Uncontrolled alcohol/drug abuse – Unsupervised dementia/psychosis Unsupervised dementia/psychosis

Signs of Warfarin Signs of Warfarin Signs of Warfarin Signs of Warfarin Overdosage Overdosage

Any unusual bleeding:

Any unusual bleeding:

– Blood in stools or urine Blood in stools or urine – Excessive menstrual bleeding Excessive menstrual bleeding Excessive menstrual bleeding Excessive menstrual bleeding – Bruising Bruising E i bl d /bl di E i bl d /bl di – Excessive nose bleeds/bleeding gums Excessive nose bleeds/bleeding gums – Persistent oozing from superficial injuries Persistent oozing from superficial injuries – Bleeding from tumor, ulcer, or other Bleeding from tumor, ulcer, or other lesion lesion

Managing Patients with High I NR Managing Patients with High I NR Managing Patients with High I NR Managing Patients with High I NR Values/ Minor or No Bleeding Values/ Minor or No Bleeding

Clinical Situation

INR >therapeutic range but <5.0, li i ll i ifi t

Guidelines

Lower the dose or omit the next dose; resume f i th t l d h th INR no clinically significant bleeding, rapid reversal not indicated for reasons of surgical intervention warfarin therapy at a lower dose when the INR approaches desired range If the INR is only minimally above therapeutic range, d d ti t b intervention dose reduction may not be necessary Patients with no additional risk factors for bleeding;

• mit the next dose or two of warfarin, monitor INR

INR >5.0 but <9.0, no clinically significant bleeding more frequently, and resume warfarin therapy at a lower dose when the INR is in therapeutic range Patients at increased risk of bleeding: omit the next g g dose of warfarin, and give vitamin K1 (1.0 to 2.5 mg

• rally)

Patients requiring more rapid reversal before urgent d l i i i K (2 4 surgery or dental extraction: vitamin K1 (2–4 mg

• rally); if the INR remains high at 24 h, an additional

dose of 1–2 mg

Managing Patients with High I NR Managing Patients with High I NR Managing Patients with High I NR Managing Patients with High I NR Values/ Serious Bleeding Values/ Serious Bleeding

Clinical Situation Guidelines

INR >9.0, no clinically significant bleeding Vitamin K1 (3–5 mg orally); closely monitor the INR; if the INR is not substantially reduced by 24–24 h, the vitamin K1 dose can be repeated S i bl di j f i d ( INR Serious bleeding, or major warfarin overdose (e.g., INR >20.0) requiring very rapid reversal of anticoagulant effect: Vitamin K1 (10 mg by slow IV infusion), with fresh plasma transfusion or prothrombin complex Life threatening bleeding or fresh plasma transfusion or prothrombin complex concentrate, depending upon urgency; vitamin K1 injections may be needed q12h Prothrombin complex concentrate, with vitamin K1 (10 Life-threatening bleeding or serious warfarin overdose Prothrombin complex concentrate, with vitamin K1 (10 mg by slow IV infusion); repeat if necessary, depending upon the INR Continuing warfarin therapy indicated after high doses of vitamin K1 Heparin, until the effects of vitamin K1 have been reversed, and patient is responsive to warfarin

Risk of I ntracranial Hemorrhage in Risk of I ntracranial Hemorrhage in Outpatients Outpatients

Hylek, et al, studied the risk of intracranial hemorrhage in outpatients treated Hylek, et al, studied the risk of intracranial hemorrhage in outpatients treated with warfarin They determined that an intensity of anticoagulation expressed with warfarin They determined that an intensity of anticoagulation expressed

Adapted from: Hylek EM, Singer DE, Ann Int Med Adapted from: Hylek EM, Singer DE, Ann Int Med 1994 1994; ;120 120: :897 897-

• 902

902

with warfarin. They determined that an intensity of anticoagulation expressed with warfarin. They determined that an intensity of anticoagulation expressed as a prothrombin time ratio (PTR) above as a prothrombin time ratio (PTR) above 2 2. .0 0 (roughly corresponding to an (roughly corresponding to an INR of INR of 3 3. .7 7 to to 4 4. .3 3) resulted in an increase in the risk of bleeding. ) resulted in an increase in the risk of bleeding.

Lowest Effective I ntensity for Warfarin Lowest Effective I ntensity for Warfarin Therapy for Stroke Prevention in Atrial Therapy for Stroke Prevention in Atrial Fibrillation Fibrillation

INR below 2 0 results in a higher risk of

Hylek EM, et al. NEJM Hylek EM, et al. NEJM 1996 1996; ;335 335: :540 540-

• 546

546. . Hylek EM, et al. NEJM Hylek EM, et al. NEJM 1996 1996; ;335 335: :540 540-

• 546

546. .

INR below 2.0 results in a higher risk of stroke

Warfarin: Current Warfarin: Current Warfarin: Current Warfarin: Current I ndications/ I ntensity I ndications/ I ntensity

I ndication I ndication I NR I NR Range Range Target Target

Prophylaxis of venous thrombosis (high Prophylaxis of venous thrombosis (high risk surgery) risk surgery) 2 0 3 0 2 5 Prophylaxis of venous thrombosis (high Prophylaxis of venous thrombosis (high-

• risk surgery)

risk surgery) 2.0–3.0 2.5 Treatment of venous thrombosis Treatment of venous thrombosis Treatment of PE Treatment of PE P ti f t i b li P ti f t i b li Prevention of systemic embolism Prevention of systemic embolism Tissue heart valves Tissue heart valves AMI (to prevent systemic embolism) AMI (to prevent systemic embolism) Valvular heart disease Valvular heart disease Atrial fibrillation Atrial fibrillation Mechanical prosthetic valves (high risk) Mechanical prosthetic valves (high risk) 2 5–3 5 3 0 Mechanical prosthetic valves (high risk) Mechanical prosthetic valves (high risk) 2.5 3.5 3.0 Certain patients with thrombosis Certain patients with thrombosis and the antiphospholipid syndrome and the antiphospholipid syndrome AMI (to prevent recurrent AMI) AMI (to prevent recurrent AMI) AMI (to prevent recurrent AMI) AMI (to prevent recurrent AMI) Bileaflet mechanical valve in aortic position, NSR Bileaflet mechanical valve in aortic position, NSR 2 2. .0 0– –3 3. .0 2 2. .5 5

Examples of Low & High Risk I nvasive Examples of Low & High Risk I nvasive P d & Cli i l C diti P d & Cli i l C diti Procedures & Clinical Conditions Procedures & Clinical Conditions

Risk of Bleeding

Low High sis Low

Dental; cutaneous biopsies;

• pen procedures; cataracts

Major thoracic, abdominal, or pelvic surgery; CNS surgery; polypectomy via colonoscopy

hrombos

AF; valvular heart disease ± aortic prosthesis; old DVT/PE AF; valvular heart disease ± aortic prosthesis; old DVT/PE

Risk of Th

Dental; cutaneous biopsies;

• pen procedures; cataracts

Prosthetic valves esp in mitral Major thoracic, abdominal, or pelvic surgery; CNS surgery; polypectomy via colonoscopy

High R

Prosthetic valves, esp. in mitral position; AF + history of CVA; very recent DVT/PE Prosthetic valves, esp. in mitral position; AF + history of CVA; very recent DVT/PE

Dosage Adjustment Algorithm Dosage Adjustment Algorithm

Current Daily Dose (mg) Current Daily Dose (mg)

2. .0 5 5. .0 7 7. .5 5 10 10. .0 12 12. .5 5

Warfarin Warfarin INR INR Dose Adjustment* Dose Adjustment* Adjusted Daily Dose (mg) Adjusted Daily Dose (mg)

1 0-2 0 Increase x Increase x 2 2 days days 5 0 7 5 10 10 0 12 12 5 15 15 0 1.0 2.0 Increase x Increase x 2 2 days days 5.0 7.5 10 10.0 12 12.5 15 15.0 2. .0 0-

• 3

3. .0 No change No change — — — — — — — — — 3. .0 0-

• 6

6. .0 Decrease x Decrease x 2 2 days days 1 1. .25 25 2 2. .5 5 5 5. .0 7 7. .5 5 10 10. .0 6.0-10 10.0† Decrease x Decrease x 2 2 days days 1.25 25 2.5 5.0 7.5 6.0 10 10.0 Decrease x Decrease x 2 2 days days 1.25 25 2.5 5.0 7.5 10 10. .0 0-

• 18

18. .0 0§ Decrease x Decrease x 2 2 days days 2 2. .5 5 >18 18. .0 0§ Discontinue warfarin Discontinue warfarin and consider hospitalization/reversal and consider hospitalization/reversal

• f anticoagulation
• f anticoagulation

g

† † Consider oral vitamin K,

Consider oral vitamin K, 2 2. .5 5– –5 5 mg mg

§ Oral vitamin K,

Oral vitamin K, 2 2. .5 5– –5 5 mg mg * Allow * Allow 2 2 days after dosage change for clotting factor equilibration. Repeat prothrombin time days after dosage change for clotting factor equilibration. Repeat prothrombin time 2 2 days after days after increasing or decreasing warfarin dosage and use new guide to management (INR = International Normalized increasing or decreasing warfarin dosage and use new guide to management (INR = International Normalized increasing or decreasing warfarin dosage and use new guide to management (INR International Normalized increasing or decreasing warfarin dosage and use new guide to management (INR International Normalized Ratio). After increase or decrease of dose for two days, go to new higher (or lower) dosage level (e.g., if Ratio). After increase or decrease of dose for two days, go to new higher (or lower) dosage level (e.g., if 5 5.0 0 qd, qd, alternate alternate 5 5. .0 0/ /7 7. .5 5; if alternate ; if alternate 2 2. .5 5/ /5 5. .0 0, increase to , increase to 5 5. .0 0 qd). qd).

Drug I nteractions with Drug I nteractions with Drug I nteractions with Drug I nteractions with Warfarin: Potentiation Warfarin: Potentiation

Level of Evidence Potentiation

Alcohol (if concomitant liver disease) amiodarone (anabolic steroids, cimetidine,† clofibrate, cotrimoxazole, erythromycin, fluconazole, isoniazid [600 mg daily] metronidazole), miconazole, omeprazole, phenylbutazone, piroxicam propafenone propranolol † sulfinpyrazone (biphasic with later

I

piroxicam, propafenone, propranolol,† sulfinpyrazone (biphasic with later inhibition) Acetaminophen , chloral hydrate , ciprofloxacin, dextropropoxyphene, di lfi it l i idi h t i (bi h i ith l t i hibiti )

II

disulfiram, itraconazole, quinidine, phenytoin (biphasic with later inhibition), tamoxifen, tetracycline, flu vaccine Acetylsalicylic acid, disopyramide, fluorouracil, ifosflhamide, ketoprofen, i t ti t l i i i lidi i id fl i fl i

III

iovastatin, metozalone, moricizine, nalidixic acid, norfloxacin, ofloxacin, propoxyphene, sulindac, tolmetin, topical salicylates Cefamandole, cefazolin, gemfibrozil, heparin, indomethacin, sulfisoxazole

III IV

†In a small number of volunteer subjects, an inhibitory drug interaction

• ccurred.

Drug I nteractions with Drug I nteractions with Drug I nteractions with Drug I nteractions with Warfarin: I nhibition Warfarin: I nhibition

Level of Evidence Inhibition Barbiturates, carbamazepine, chlordiazepoxide, I cholestyramine, griseofulvin, nafcillin, rifampin, sucralfate Di l illi A hi i l i i II Dicloxacillin Azathioprine, cyclosporine, etretinate, trazodone III IV IV

Drug I nteractions with Drug I nteractions with Drug I nteractions with Drug I nteractions with Warfarin: No Effect Warfarin: No Effect

Level of Evidence No Effect Alcohol, antacids, atenolol, bumetadine, enoxacin, I famotidine, fluoxetine, ketorolac metoprolol, naproxen, nizatidine, psyllium, ranitidine‡ Ib f k l I Ibuprofen, ketoconazole II III Diltiazem, tobacco, vancomycin IV

Effective Patient Effective Patient Effective Patient Effective Patient Education Education

Teach basic concepts of safe,

Teach basic concepts of safe, effective anticoagulation effective anticoagulation

Discuss importance of regular INR

Discuss importance of regular INR

Discuss importance of regular INR

Discuss importance of regular INR monitoring monitoring C l f h di i C l f h di i

Counsel on use of other medications,

Counsel on use of other medications, alcohol alcohol

Develop creative strategies for

Develop creative strategies for improving compliance improving compliance improving compliance improving compliance

Factors I nfluencing Factors I nfluencing Factors I nfluencing Factors I nfluencing Variability Variability

Patient/Disease State Process of Care Warfarin: drug with a narrow therapeutic i d index

Antithrombotic agents in CHF Antithrombotic agents in CHF Antithrombotic agents in CHF Antithrombotic agents in CHF

Anti

Anti-

• coagulation is firmly indicated in CHF

coagulation is firmly indicated in CHF with atrial fibrillation a previous with atrial fibrillation a previous with atrial fibrillation, a previous with atrial fibrillation, a previous thromboembolic event or a mobile LV thromboembolic event or a mobile LV thrombus thrombus thrombus thrombus

After a prior MI. either aspirin or oral anti

After a prior MI. either aspirin or oral anti-

• c0agulation are recommended as a

agulation are recommended as a c0agulation are recommended as a agulation are recommended as a secondary prophylaxix. secondary prophylaxix.

Aspirin should be avoide I patient with

Aspirin should be avoide I patient with

Aspirin should be avoide I patient with

Aspirin should be avoide I patient with recurrent hospitalization because df recurrent hospitalization because df worsening heart failure. worsening heart failure. g

Anticoagulation is recommende Anticoagulation is recommende g in the following situations in the following situations

Lifelong for all patients with

Lifelong for all patients with mechanical valves and for patients mechanical valves and for patients with bioprosthesis who have other with bioprosthesis who have other p indicastion for anti indicastion for anti-

• coagulation

coagulation For the first For the first 3 months after insertion in months after insertion in

For the first

For the first 3 3 months after insertion in months after insertion in all patients with bioprosthesis with a all patients with bioprosthesis with a target INR of target INR of 2 2. .5 5

Target I NR for Mechanical Prosthesis Target I NR for Mechanical Prosthesis Target I NR for Mechanical Prosthesis Target I NR for Mechanical Prosthesis

Patient -related risk factors Prosthesis Prosthesis thrombogenicity thrombogenicity

No risk factor No risk factor > > 1 1 risk factor risk factor

Patient related risk factors thrombogenicity thrombogenicity

Low Low 2 2. .5 5 3 3. .0 Medium Medium 3 0 3 5 Medium Medium 3.0 3.5 High High 3 3. .5 5 4 4. .0

Patient Characteristics Recommendation

Bileaflet mechanical valve in the aortic position, Goal INR 2.5; range, 2.0–3.0 left atrium of normal size NSR normal ejection fraction left atrium of normal size, NSR, normal ejection fraction Tilting disk valve or bileaflet mechanical valve in Goal INR 3.0; range, 2.5–3.5* the mitral position Bileaflet mechanical aortic valve and AF Goal INR 3.0; range, 2.5–3.5* Caged ball or caged disk valves Goal INR 3.0; range, 2.5–3.5(+) aspirin therapy (80–100 mg/d) aspirin therapy (80 100 mg/d) Additional risk factors Goal INR 3.0; range, 2.5–3.5; and aspirin therapy (81 mg/d) Systemic embolism, despite adequate therapy Goal INR 3.0; range, 2.5–3.5; with oral anticoagulants and aspirin therapy (81 mg/d)

* Alternative: goal INR 2.5; range, 2.0–3.0; and aspirin therapy (80–100 mg/d)

The Warfarin, Aspirin, The Warfarin, Aspirin, Reinfarction Study (WARI S I I ) Reinfarction Study (WARI S I I )

Was a randomised , multicenter trial conducted in

Was a randomised , multicenter trial conducted in 3630 3630 patients with recent MI (WHO criteria) patients with recent MI (WHO criteria) patients with recent MI (WHO criteria) . patients with recent MI (WHO criteria) .

1216

1216 patients received warfarin (target INR patients received warfarin (target INR 2 2.8-4 4.2), ),

1206

1206 received received 160 160 mg aspirin daily mg aspirin daily g p y g p y

1208

1208 received received 75 75 mg aspirin daily plus warfarin (target mg aspirin daily plus warfarin (target INR INR 2 2.0-2 2.5). T ). T

The treatment was started before discharge from the

The treatment was started before discharge from the

• hospital. Patients were all below
• hospital. Patients were all below 75

75 years and were years and were followed for approximately followed for approximately 4 years (average) years (average) followed for approximately followed for approximately 4 4 years (average). years (average).

• Approximately

Approximately 59 59 % of the patients had a Q % of the patients had a Q-

• wave

wave infarction and infarction and 54 54 % were treated with thrombolysis % were treated with thrombolysis y

• Mean ejection fraction was

Mean ejection fraction was 52 52 %. %. 77 77 % received statins % received statins and and 74 74 % beta % beta-

• blockers.

blockers.

Primary Endpoints Primary Endpoints y p y p

composite of death, reinfarction of thromboembolic

composite of death, reinfarction of thromboembolic stroke occurred in: stroke occurred in: stroke occurred in: stroke occurred in:

20

20. .0 0 % % in the in the aspirin group aspirin group ( p value NS) ( p value NS) 16 16 7 % i h i h f i f i ( l NS) ( l NS)

16

16.7 7 % in the in the warfarin group warfarin group ( p value NS) ( p value NS)

15

15. .0 0 % % in the in the warfarin+ aspirin group warfarin+ aspirin group ( p value s) ( p value s)

Episodes of major, non

Episodes of major, non-

• fatal bleeding were seen

fatal bleeding were seen significantly more often in the two warfarin groups significantly more often in the two warfarin groups d t th i i l d t th i i l compared to the aspirin alone group. compared to the aspirin alone group.

There was no difference in mortality between the

There was no difference in mortality between the Th diff i th i d i t Th diff i th i d i t

• groups. The difference in the primary endpoint was
• groups. The difference in the primary endpoint was

driven by a significant reduction in reinfarction and driven by a significant reduction in reinfarction and thromboembolic stroke in the warfarin groups thromboembolic stroke in the warfarin groups thromboembolic stroke in the warfarin groups. thromboembolic stroke in the warfarin groups.

Th k Th k Thank you Thank you y