What Goes Together: Peanut Butter & Jam, Cookies & Milk - - PowerPoint PPT Presentation

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What Goes Together: Peanut Butter & Jam, Cookies & Milk Antiplatelets & Anticoagulants???

Lily Lin and Kevin Kwok LMPS Pharmacy Residents December 10, 2019 Preceptor: Elaine Lum

Learning Objectives

• Review the mechanism of action of antiplatelets and

anticoagulants

• List the indications and review the guidelines and/or

evidence for combination therapy of anticoagulants and antiplatelets

• Describe an approach in applying guideline

recommendations and evidence to a patient who may require combination therapy

Cardiovascular Disease (CVD) Treatment

• Antiplatelet therapy indicated for secondary

prophylaxis of atherosclerotic disease

• Anticoagulant therapy has specific indications

such as atrial fibrillation or venous thromboembolic disease

Antithrombotic Drugs

Antiplatelets: prevent platelets from clumping Anticoagulants: reduces fibrin formation and prevents clots from growing

Antiplatelet Therapy

• Primary therapy used to prevent arterial

thrombosis in patients with atherosclerotic disease

• Dual antiplatelet therapy (aspirin + P2Y12

receptor inhibitor): treatment for ACS with stenting, elective PCI with stenting, stroke

Antiplatelets: Mechanism of Action

Aspirin irreversibly inhibits cyclooxygenase-1 and prevents platelet dependent thromboxane formation P2Y12 Receptor Inhibitors prevent platelet activation by inhibiting binding to adenosine diphosphate (ADP)

• Clopidogrel and prasugrel: irreversible inhibition
• Ticagrelor: reversible inhibition

Anticoagulant Therapy

• Commonly indicated for treatment/prevention of venous

thromboembolism and stroke prophylaxis in atrial fibrillation

• Includes variety of agents that inhibit different parts of

coagulation cascade ○ Vitamin K antagonism ○ Direct thrombin inhibition ○ Direct factor Xa inhibition

Oral Anticoagulants

• Vitamin K antagonists (warfarin)

○ Inhibit vitamin K epoxide reductase → block hepatic synthesis of active vitamin K

• Direct thrombin inhibitors (dabigatran)

○ Prevent thrombin from cleaving fibrinogen → fibrin

• Direct factor Xa inhibitors (apixaban, rivaroxaban,

edoxaban)

• Prevent factor Xa from cleaving prothrombin to thrombin

Dual Antiplatelet Therapy (DAPT) in PCI

• Used in patients who undergo percutaneous

coronary intervention with stenting for acute coronary syndrome (ACS) and non-ACS indications (“elective”)

• DAPT significantly lowers the risk of stent

thrombosis

What do the guidelines recommend for DAPT in PCI?

CCS Guidelines for Elective PCI (2018)1

CCS Guidelines for STEMI/NSTEMI (2018)1

Why do DAPT and not single antiplatelet therapy?

Stent Thrombosis post-PCI

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DAPT: P2Y12I + ASA

CURE (2001)2 Clopidogrel 300mg po loading dose then 75mg po + ASA reduce mortality, non- fatal MI, stroke vs. ASA alone post ACS (NSTEMI/UA) Conclusion: DAPT > SAPT post ACS (NSTEMI/UA) PCI-CURE (2001)3 In patients with NSTEMI undergoing PCI, clopidogrel 75mg + ASA x 3-12 months reduce CV death, MI, revascularization vs. ASA. Based on this trial, guidelines suggest 12 month DAPT after ACS and PCI. TRITON-TIMI 38 (2007)4 In patients with ACS (STEMI/NSTEMI) and scheduled PCI, prasugrel 60mg po loading dose then 10mg po + ASA reduce CV mortality and morbidity but increase bleeding vs. clopidogrel 75mg po + ASA PLATO (2009)5 In patients with ACS (STEMI/NSTEMI), ticagrelor 180mg po loading dose then 90mg BID po + ASA reduce CV death, MI, stroke without increasing bleeding vs. clopidogrel 75mg po + ASA

N Engl J Med 2001; 345:494-502 Lancet 2001; 358: 527–33 N Engl J Med 2007; 357:2001-2015 N Engl J Med 2009; 361:1045-1057

Should therapy be extended beyond 1 year post-PCI?

DAPT (2014)6

P (N=9961) Undergoing PCI with stent or had PCI with stent in prior 3 days 62yo, 31% prior PCI, 12% prior CABG Indication for PCI: 11% STEMI, 16% NSTEMI, 17% UA, 38% stable angina P2Y12: 65% clopidogrel, 35% prasugrel I DAPT: ASA 75-162mg daily plus clopidogrel 75mg daily or prasugrel 10mg daily for another 18 months after 12 months of DAPT C SAPT: ASA 75-162mg daily + placebo after 12 months of DAPT O Primary outcomes:

• Stent thrombosis: 0.4% vs 1.4% ARR 1% NNT 100
• All-cause mortality, MI or stroke: 4.3% vs 4.9% ARR 0.6% NNT 62
• Moderate or severe bleeding (GUSTO criteria): 2.5% vs 1.6% ARR 0.9% NNH 111

Bottom Line: Extended DAPT (ASA and clopidogrel OR prasugrel) decreases stent thrombosis but increases bleeding risk (moderate-severe) and all cause

• mortality. Weigh risk vs. benefit before extending DAPT duration.

What about ticagrelor? Does extended duration provide any benefit? What dose should be used if extending therapy beyond 1 year post ACS?

PEGASUS-TIMI (2015)7

P ≥ 50 y/o, MI 1-3 years prior, ≥ 1 of: ≥ 65, diabetes requiring medical therapy, second prior MI, multivessel CAD, CKD with CrCl < 60mL/min Baseline: age 65, 59% multivessel CAD, 16% > 1 previous MI, 83% PCI history Medications: 99.8% ASA, 93% statin, 82% beta-blocker, ACE/ARB 81% I Ticagrelor 90mg BID OR Ticagrelor 60mg BID C Placebo All patients received ASA 75 to 150mg daily O Primary - CV mortality, MI or stroke at three years Ticagrelor 90mg BID vs. placebo: 7.85% vs. 9.04% (HR 0.85, CI 0.75-0.96, p=0.008) Ticagrelor 60mg BID vs. placebo: 7.77% vs. 9.04% (HR 0.84, CI 0.74-0.95, p=0.004) Secondary - TIMI major bleeding Ticagrelor 90mg BID vs. placebo: 2.6 vs. 1.06% (HR 2.59, NNH 65) Ticagrelor 60mg BID vs. placebo: 2.3% vs. 1.06% (HR 2.32, NNT 81)

Primary Outcome (CV mortality, MI, stroke)

** Kaplan Meier Rates through 3

• years. Study drugs were

administered twice daily.

PEGASUS-TIMI: Conclusion

• Adding ticagrelor to ASA in stable CAD patients

reduced the risk of CV death, MI or stroke

• Both doses of ticagrelor had similar efficacy and

increased bleeding Bottom line: weigh risk and benefits before extending

• DAPT. Use lower dose (60mg BID) if extending DAPT.

Note: 60mg NOT covered by PharmaCare

CCS Guidelines (2018)1

Do we use DAPT post coronary artery bypass graft (CABG)?

DAPT Post-CABG

Overall, more literature to support effect of clopidogrel + ASA (vs. ASA monotherapy) in maintaining post-

• perative vein graft patency after OFF-pump CABG8

Note: Use of ticagrelor and prasugrel explored in post-hoc analyses of PLATO and TRITON-TIMI 38 trials, respectively, but no prospective randomized data available.

What are the guideline recommendations for DAPT post-CABG? How long do we treat for?

Antithrombotics Post CABG (AHA Guidelines)8

• Circulation. 2015;131:927-964

Bottom Line: ASA should be continued for life in all CABG patients. Depending on if patient is: 1) off-pump CABG: ASA 81mg daily + Clopidogrel 75mg daily x 1yr (strong recommendation) 2) on-pump CABG: consider ASA 81mg daily + Clopidogrel 75mg daily x1yr (weaker recommendation)

What do we do in patients requiring an oral anticoagulant (e.g. atrial fibrillation, mechanical valve) and have undergone PCI? Is triple therapy (OAC + DAPT) safe? How does dual therapy (OAC + single antiplatelet) compare?

WOEST (2013)9

P (n=563) Adults, indication for OAC for ≥ 1 year after study, severe coronary lesion with indication for PCI Baseline: age 70 years, Indication for OAC: 69% atrial fibrillation/atrial flutter, 10% mechanical valve, 20% other (eg, apical aneurysm or PE) I Clopidogrel 75mg + warfarin (titrated to INR 2) C Clopidogrel 75mg + ASA 80-100mg + warfarin (titrated to INR 2) O Primary:

• Any bleeding by year 1: 19.4% vs. 44.4% (HR 0.39, CI 0.26-0.50, NNT 4)

Secondary:

• Stent thrombosis NSS (1.4% vs. 3.2%. HR 0.44, CI 0.14-1.44)
• Death: 2.5% vs. 6.3% (HR 0.39, CI 0.16-0.93, p=0.027, NNT 26)
• Lancet. 2013 Mar 30;381(9872):1107-15

Primary Outcome (Any Bleeding by Year 1)

WOEST: Limitations

• Unclear why bleeding rates so high in study
• Low rate of proton pump inhibitors in this population
• Underpowered to detect differences in stent

thrombosis

• Broad indication for oral anticoagulants

WOEST: Conclusion/Bottom Line

Strategy of oral anticoagulant and single antiplatelet therapy (P2Y12I) appears to reduce bleeding risk vs. triple therapy. Bottom Line: In patients with an indication for OAC and have undergone PCI, addition of single antiplatelet (clopidogrel) is safer than DAPT (ASA + clopidogrel). More trials required to determine efficacy (stent thrombosis, stroke, myocardial infarction)

Atrial Fibrillation and PCI

• Increased risk of bleeding when anticoagulation is

added to antiplatelet therapy

• Stent thrombosis and ischemic stroke must be balanced

with risk of bleeding 2 General Approaches to managing AF and PCI:

• Dual therapy: OAC + P2Y12 inhibitor
• Triple therapy (TT): OAC + DAPT

AF and PCI: Trials to Date

• 1. PIONEER AF-PCI (2016)
• 2. RE-DUAL PCI (2017)
• 3. ENTRUST-AF PCI (2019)
• 4. AUGUSTUS (2019) *included medically managed patients*

PIONEER-AF PCI (2016)10

P (n=2124) ≥ 18 y/o with non-valvular AF who had just undergone PCI with stent placement Baseline: 70 y/o, 12% STEMI, 22% UA, 18% NSTEMI, 61% elective PCI, 39% urgent PCI. 93% clopidogrel, 2% prasugrel, 5% ticagrelor I Dual therapy: Rivaroxaban 10-15mg (10mg if CrCl 30-50mL/min) daily + P2Y12 inhibitor x 12 months OR Triple therapy: Rivaroxaban 2.5mg BID + DAPT x 1, 6 or 12m (P2Y12I dropped). Step down: Rivaroxaban 10-15mg daily + ASA until 12m post stent C Triple therapy: Warfarin + DAPT x 1m, 6m, or 12m (P2Y12I dropped) O 1º - Clinically significant bleeding (16.8% vs. 18% vs. 26.7%): both rivaroxaban groups significantly decreased bleeding vs. warfarin group 2º - NSS stent thrombosis, NSS CV mortality, MI or stroke

N Engl J Med 2016; 375:2423-2434

Panel A: Primary Safety Endpoint: Composite of major bleeding

• r minor bleeding according to TIMI criteria or bleeding

requiring medical attention Panel B: Secondary Efficacy Endpoint: Composite of death from cardiovascular causes, myocardial infarction, or stroke

PIONEER-AF PCI: Limitations

• Doses used not demonstrated to reduce

stroke in patients with AF

• Study not powered to evaluate thrombotic

events or clinical efficacy

• Based on results from WOEST trial, why

was warfarin + single antiplatelet therapy not evaluated?

PIONEER-AF PCI: Conclusion

Builds on WOEST’s conclusion that anticoagulant + single antiplatelet therapy appears to be safer than warfarin triple therapy without compromising efficacy Although RIVA 2.5mg BID TT was demonstrated to be safer than warfarin TT, study does not address ideal duration of triple therapy with DOAC

Bottom line: Consider rivaroxaban 10-15mg + P2Y12I or rivaroxaban 2.5mg BID + ASA + P2Y12I over warfarin triple

• therapy. Note: RIVA 2.5mg and 10mg tabs are NOT covered

by Pharmacare.

RE-DUAL (2017)11

P (n=2725) Non-valvular AF, unstable or stable CAD treated with PCI Baseline: Age 72 years, 43.7% stable angina, 48.4% ACS 86% clopidogrel, 12% ticagrelor I Dabigatran 150mg BID plus P2Y12I OR Dabigatran 110mg BID plus P2Y12I C Triple therapy (aspirin, P2Y12I, warfarin with INR target 2-3)

• ASA dropped 1m post BMS and 3m post DES

O 1º - ISTH major bleeding or clinically relevant non-major bleeding: DABI 110mg BID vs. warfarin (15.4% vs. 26.9%) (HR 0.52, CI 0.45-0.63) DABI 150mg BID vs. warfarin (20.2% vs. 25.7%) (HR 0.72, CI 0.58-0.88) 2º - Trend towards increased thromboembolic events/death in DABI 110mg BID group vs. warfarin, NSS (11.1% vs. 8.5%, CI 0.98-1.73). Not seen in DABI 150mg BID group.

N Engl J Med 2017; 377:1513-1524

Secondary Efficacy End Point: Composite of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization

RE-DUAL PCI: Conclusions

Builds on past trials that support use of OAC + single antiplatelet therapy over triple therapy with warfarin Dabigatran 150mg BID or 110mg BID + P2Y12I may be preferable to triple therapy with warfarin. Bottom line: Consider dabigatran dual therapy (110 or 150mg BID) over warfarin triple therapy.

ENTRUST AF-PCI (2019)12

P (n=1506) Non-valvular AF, previous PCI for stable CAD or ACS Baseline: Age 69 years, 48% stable CAD, 52% ACS 93% clopidogrel, 7% ticagrelor I Edoxaban 60 or 30 daily (one or more of: CrCl 15-50mL/min, ≤ 60kg, use of potent P-glycoprotein inhibitors) + clopidogrel 75 daily (or prasugrel/ticagrelor) x 12 months (dual therapy) C Warfarin (INR 2-3) + clopidogrel 75 daily (or prasugrel/ticagrelor) x 12 months + ASA x (minimum 1 month up to 12 months) (triple therapy) O 1º - Major or clinically relevant non-major bleeding: · Edoxaban vs warfarin: 17% vs 20% NSS 2º - CV death, stroke, systemic embolic event, MI, definite stent thrombosis: · Edoxaban vs warfarin: 7% vs 6% NSS

Conclusion

Edoxaban was noninferior to warfarin in terms of bleeding and efficacy (ischemic events, stent thrombosis, death). Bottom line: edoxaban dual therapy was only DOAC to only show noninferiority and not superiority compared to warfarin triple therapy. Given this and the fact that edoxaban is not currently covered by Pharmacare, consider using other DOACs first.

AUGUSTUS (2019)13

P (n=4,614) Recent ACS or PCI with planned P2Y12I ≥ 6m, AF Baseline: mean age 70, CHADS-VASc 3.9, mean HAS-BLED 2.9 38% ACS and PCI, 23.8% ACS medical therapy, 38.2% elective PCI, 6.7 days from index event to randomization I Randomization 1: Apixaban (5mg BID or 2.5mg BID if 2 or more of: ≥ 80y/o, SCr ≥ 133umol/L, weight ≤ 60kg)

• vs. warfarin (INR 2-3)

Randomization 2: Aspirin vs. placebo All patients received background P2Y12I (93% clopidogrel, 5.4% ticagrelor, 1.2% prasugrel) Follow-up: 6 months O Primary: Bleeding

• APIX vs. warfarin: 10.5% vs. 14.7%; HR 0.69 (CI 0.58-0.81)
• ASA vs. placebo: 16.1 vs. 9.0%; HR 1.89 (CI 1.59-2.24)

Secondary:

• Apixaban decreases death or hospitalization
• NSS for all secondary outcomes between aspirin and placebo

Conclusion: dual therapy with APIX and P2Y12I decreases bleed risk, improves cardiac outcomes N Engl J Med 2019; 380:1509-1524

American Heart Association. 200 (2018) 17-23

AUGUSTUS: Conclusions

• First DOAC AF/ACS trial to show that the addition of aspirin in

triple therapy INCREASES bleeding events

• In line with previous trials’ conclusion that dual therapy is safer

and as effective as triple therapy

• Considerations: time in therapeutic range in warfarin group

59% (lower than other RCT’s), 90% of patients on clopidogrel Bottom Line: Consider an antithrombotic regimen of apixaban + P2Y12I in AF patients with had either ACS (medically managed/PCI) or have undergone elective PCI.

Our Conclusion Considerations

WARFARIN (OAC and PCI) Based on WOEST, dual therapy > triple therapy for safety outcomes RIVA (AF and PCI) Dual therapy (reduced dose RIVA 10/15mg + P2Y12I) and triple therapy (low dose RIVA 2.5mg BID + P2Y12I + ASA) > Warfarin TT for safety

• utcomes

Pharmacare SA for non- valvular AF: RIVA 15 and 20mg tablets DABI 110 and 150mg tablets APIX 2.5 and 5mg tablets

DABI (AF and PCI) DABI 110mg/150mg BID + P2Y12I > warfarin TT for safety outcomes APIX (AF and PCI/ACS) Apixaban (2.5mg BID or 5mg BID) + P2Y12I > warfarin TT for safety outcomes. Addition of ASA to therapy increases bleed risk EDOX (AF and PCI) Edoxaban (30-60mg) non-inferior to warfarin for safety outcomes

Triple Therapy: 1. Warfarin (INR 2-2.5) + ASA + clopidogrel. 2. RIVA 2.5mg BID + ASA +

• clopidogrel. Increase RIVA to

10-15mg when ASA discontinued. Dual Therapy: 1. RIVA 10-15mg + clopidogrel. Increase RIVA to 20mg when P2Y12I discontinued. 2. DABI 110mg/150mg BID + clopidogrel

**NOTE: Guidelines do not reflect findings from the AUGUSTUS trial (2019).

2018 CCS Atrial Fibrillation Guidelines14

Stable CAD + Atrial Fibrillation

AFIRE (2019)15

P (n=2215) Atrial fibrillation, CHADS2 ≥1, no history of stent thrombosis, and ≥1 of: history of PCI more than 1 year, history of CABG more than 1 year, history of angiographically confirmed CAD with stenosis ≥50% not requiring revascularization 74 years old, 71% had a previous PCI, 11% had previous CABG I Combo therapy: Rivaroxaban 15mg or 10mg (CrCl 15-49) daily + antiplatelet (ASA or P2Y12) C Monotherapy: Rivaroxaban 15mg or 10mg (CrCl 15-49) daily alone O 1°: Stroke, systemic embolism, MI, UA requiring revasc, death from any cause: · Monotherapy vs combo therapy: 4.1% vs 5.8% ARI 1.7% NNH 59 Major bleeding (ISTH definition) · Monotherapy vs combo therapy: 1.6% vs 2.8% ARI 1.2% NNH 84

N Engl J Med 2019; 381:1103-1113

Limitations

• Open-label design
• Early trial termination
• Rivaroxaban dose used in this trial is not the

indicated dose for atrial fibrillation in North America

Conclusion

There was increased bleeding and no additional benefit in terms of efficacy endpoints (stroke, MI, SE, need for revasc, death from any cause) with the addition of an antiplatelet (ASA or P2Y12) to rivaroxaban (15 or 10mg daily). Bottom Line: Addition of ASA in patients with stable CAD (≥ 1 year post PCI, CABG) who are treated with DOAC for atrial fibrillation increases risk of bleeding without additional benefit

Warfarin + ASA in Stable CAD

WARIS II (2002)16

Patients (n=3630) Age 20-74 y/o, hospitalized for acute MI Exclusion: malignancy, contrainidications to therapy, potential non-compliance I/C Intervention A: warfarin (target INR 2.8-4.2; mean 2.8) Intervention B: ASA 160mg Intervention C: ASA 75mg + warfarin (target INR of 2.0 to 2.5; mean 2.2) O Primary outcome - composite of death, reinfarction or thromboembolic stroke: 16.7% in warfarin alone, 20% in ASA 160mg, 15% in ASA + warfarin. Difference between two warfarin groups NSS Secondary outcome - nonfatal major bleeding: 2.7% in warfarin alone, 0.7% in ASA 160mg, 2.3% in ASA + warfarin

In patients post-MI, warfarin + ASA or warfarin monotherapy significantly reduce composite of death, reinfarction or thromboembolic stroke vs. ASA alone but increases nonfatal major bleeding.

Conclusion

Warfarin monotherapy and warfarin + ASA more effective than ASA monotherapy, offset by increased bleeding. No significant difference in efficacy between warfarin and warfarin + ASA.

Bottom line: Addition of ASA to warfarin may not confer additive benefit in stable CAD.

Low-dose DOAC + ASA in Stable CAD

COMPASS (2017)17

P (n=27,395) CAD and/or PAD, ≥65 years old, <65 years old AND documented atherosclerosis OR revascularization involving 2 vascular beds OR at least 2 additional risk factors (current smoker, DM, eGFR <60, CHF, non-lacunar ischemic stroke ≥1 month ago) 68 years old, 90% CAD, 27% PAD I Rivaroxaban 2.5mg BID + ASA 100mg daily (Group 1) OR Rivaroxaban 5mg BID (Group 2) C ASA 100mg daily (Group 3) O 1°: CV death, stroke, MI: · Group 1 vs group 3: 4.1% vs 5.4% ARR 1.3% NNT 77 · Group 2 vs group 3: 4.9% vs 5.4% NSS 2°: Modified ISTH criteria for major bleeding (fatal bleeding, symptomatic bleeding into critical organ, bleeding into surgical site requiring reoperation, bleeding that led to hospitalization): · Group 1 vs group 3: 3.1% vs 1.9% ARI 1.2% NNH 84 · Group 2 vs group 3: 2.8% vs 1.9% ARI 0.9% NNH 111 N Engl J Med 2017; 377:1319-1330

Limitations

Trial terminated early due to efficacy seen in RIVA + ASA group → potential overestimation

• f benefit and underestimation of safety

parameters

Conclusion

Rivaroxaban + ASA resulted in a 1.3% ARR in CV death, stroke or nonfatal MI with an NNT of 77; counteracted by increased risk in major bleeding with NNH of 84. Bottom line: Addition of low-dose rivaroxaban to ASA, in patients with stable CAD, reduces CV risk but increases risk of bleed. Consider patient specific factors and weigh risk vs. benefit

Low-dose DOAC + ASA/P2Y12I in ACS (without AF)

ATLAS-ACS (2012)18

P ≥18yo, if <55 (must have diabetes or previous MI), diagnosis of ACS (UA, NSTEMI or STEMI), within 7 days of hospital admission Meds at baseline: 99% ASA, 93% P2Y12, 66% BB, 39% ACEi/ARB, 84% statin Diagnosis: 50% STEMI, 26% NSTEMI, 24% unstable angina. 60.4% PCI/CABG for index event I Triple therapy: Rivaroxaban 2.5mg BID (Group 1) Triple therapy: Rivaroxaban 5mg BID (Group 2) C Dual therapy: Placebo (Group 3) O 1°: CV death, MI or stroke · Group 1 vs group 3: 9.1% vs 10.7% ARR 1.6% NNT 63 · Group 2 vs group 3: 8.8% vs 10.7% ARR 1.9% NNT 53 TIMI major bleeding not associated with CABG: · Group 1 vs group 3: 1.8% vs 0.6% ARI 1.2% NNH 84 · Group 2 vs group 3: 2.4% vs 0.6% ARI 1.8% NNH 56

N Engl J Med 2012; 366:9-19

Limitations

• Difficult to interpret results due to missing data

(incomplete follow-up, vital status), potential information censoring

• Study participants generally younger,

predominantly male → caution generalizing to higher risk population

Conclusion

FDA declined approval for use in ACS due to high incomplete follow-up, uncounted deaths, risk of informative censoring. Bottom Line: In patients with recent ACS, addition of low-dose rivaroxaban to standard DAPT may reduce CV mortality but increases risk of nonfatal bleeding

Prosthetic Valves

Mechanical vs. Bioprosthetic (Tissue) valves

Mechanical Valves19

Mechanical Valves19

ASA 75-100mg recommended in addition to VKA VKA (warfarin) are recommended in mechanical prosthetic valves DOACs are NOT recommended in patients with mechanical prosthetic valves INR targets:

• Mechanical mitral valve replacements: 3.0 (2.5-3.5)
• Mechanical aortic valve replacements with risk factors*: 3.0 (2.5-3.5)
• Mechanical aortic valve replacements with no risk factors: 2.5 (range 2-3)

*risk factors for thromboembolic events: AF, previous thromboembolism, LV dysfunction, hypercoagulable condition, older AVR

Bioprosthetic Valves19

Bottom line: reasonable for all patients to be on ASA 81mg daily. Anticoagulation with warfarin can be considered to achieve target INR of 2.5. Consider for at least 3 months and for as long as 6 months in patients at low risk of bleeding.

TAVR19

Bottom line: ASA 81mg daily should be continued in all patients for life. Clopidogrel 75mg daily may be considered in patients for the first 6 months. Anticoagulation with warfarin can be considered to achieve a target INR of 2.5. Consider for at least 3 months after TAVR in patients at low risk of bleeding

Treatment of LV Thrombus20

Treatment of LV Thrombus in PCI1

Bottom line: treat patients with established LV thrombus who undergo PCI with: ASA 81 mg daily for 1 day up to 6 months + Clopidogrel 75mg daily + oral anticoagulant Discontinue oral anticoagulant if evidence of LV thrombus resolution ≥3 months after PCI Then resume DAPT with ASA + clopidogrel up to 1 year after PCI

Additional Indications

• VTE treatment and prophylaxis
• PAD + lower extremity arterial stent
• Essential thrombocythemia
• Antiphospholipid syndrome

VTE Treatment in PCI1

Bottom Line: treat patients with ASA 81mg daily (for 1 day up to 6 months after PCI) + Clopidogrel 75mg daily + oral or parenteral anticoagulant (in accordance with DVT/PE recommendation). Resume DAPT with ASA + Clopidogrel for up to 1 year after PCI when oral anticoagulant discontinued

Patient requiring perioperative VTE prophylaxis

• If on chronic antiplatelet therapy, suggest pharmacologic prophylaxis (LMWH,

DOAC, fondaparinux) if risk VTE > bleeding (grade 2C)

• If anticoagulant associated with antiplatelet therapy, suggest administration of

lowest approved dose (grade 2C)

• If risk of bleeding > VTE, consider intermittent pneumatic compression without

discontinuing antiplatelet therapy

VTE Prophylaxis in Patients on Antiplatelets21

Bottom Line: consider risk of VTE vs. bleeding in patients who require VTE prophylaxis and are on chronic antiplatelet therapy. Treat patient with lowest approved dose of anticoagulant, on top of usual antiplatelet therapy, if VTE risk outweighs bleeding risk

PAD + Lower Extremity Stenting22

Bottom Line: in patients with indication for OAC, consider ASA 81mg daily + OAC for at least 1 month after stenting if at higher risk of stent thrombosis than bleeding. If patient at higher risk of bleeding, consider treating with OAC alone. Weak recommendation to continue ASA + OAC beyond 1 month

Essential Thrombocythemia23

Blood Cancer J. 2018 Jan; 8(1): 2.

Bottom Line: patients with high risk of venous thrombosis (history of thrombosis or >60 years old with JAK2/MPL mutation) should be on an oral anticoagulant. Can consider adding on ASA 81mg daily for patients with recurrent venous thrombosis

Treatment of Antiphospholipid Syndrome24

Initial stabilization of stroke and myocardial infarction not different from those without APS Secondary prophylaxis of thrombosis recurrence: inconclusive data regarding combination use of VKA and aspirin

Bottom Line: inconclusive data to suggest benefit of adding ASA to warfarin in patients with antiphospholipid syndrome

Bottom Line

Patient specific factors to consider when using combination of antiplatelet and anticoagulant therapy:

• Ischemic risk:

○ Potential consequences (stroke, DVT) ○ Concomitant medications ○ Coexisting conditions (extensive CAD, CKD, diabetes) ○ Medical history (previous MIs, stent characteristics)

• Bleeding risk:

○ Age ○ Weight ○ Risk of falls ○ Concomitant medications (NSAIDs, steroids) ○ Coexisting conditions (thrombocytopenia, CKD, anemia)

Should do it AF and ACS/PCI (WOEST, PIONEER, REDUAL, ENTRUST, AUGUSTUS) Stable CAD or PAD (COMPASS) Mechanical valves VTE treatment/prophylaxis post PCI When it’s ok Bioprosthetic valve LV Thrombus post-PCI Questionable/Uncertainty ACS without AF (ATLAS-ACS) Essential thrombocythemia Antiphospholipid syndrome Peripheral arterial disease + stenting in patients on long term OAC Post-TAVR Shouldn’t do it Stable CAD and AF (AFIRE)

Application to Clinical Practice

Questions?

Thank you!

References

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