Download Aspirin Therapy for Patients with Stable CAD

Should It Stay or Should It Go?
Aspirin Therapy for Patients with Stable CAD Post‐MI/TIA with Atrial Fibrillation on Concurrent DOAC Therapy
Erin R. Pilcher, Pharm.D.
PGY1 Pharmacy Practice Resident
Central Texas Veterans Healthcare System
01/06/2017
1
Objectives
• Provide an overview of the epidemiology, etiology, and pathophysiology of CAD
• Briefly review the evidence for benefit of aspirin therapy for patients with stable CAD
• Analyze the literature in order to provide a clinical recommendation on the use of aspirin + DOAC combination therapy for AF patients post‐
MI/TIA with stable CAD
2
Abbreviations
• ACCP –American College of Chest Physicians
• AF – atrial fibrillation
• APT – antiplatelet therapy
• ASA – acetylsalicylic acid OR aspirin
• AWP – average wholesale price
• BID – twice daily administration
• CABG ‐‐ Coronary artery bypass graft • CAD‐ coronary artery disease
• CHD – coronary heart disease
• CI – confidence interval
• CRNM – clinically relevant non‐
major
• DE – drug exposure
• DOAC‐ direct oral anticoagulant
• HDER‐ higher dose edoxaban •
•
•
•
•
•
•
•
•
•
•
regimen
HR – hazard ratio
INR – international normalized ratio
LDER‐ lower dose edoxaban regimen
MI – myocardial infarction
PCI‐ percutaneous coronary intervention RCT – randomized controlled trial
SAPT – single antiplatelet therapy
SEE – systemic embolic event
SSE – stroke and systemic embolism
TIA‐ transient ischemic attack
VKAs – vitamin K antagonists
3
CAD
Epidemiology, Etiology, and Pathophysiology 4
CAD ‐ Definition
• One or more of the following
•
•
•
•
•
Stable angina pectoris
History of unstable angina pectoris
History of PCI
CABG
Previous MI
• Stable disease
• ≥12 months since event
5
CHEST 2012; 141(2)(Suppl):e637S–e668S
Epidemiology
• Major cause of death and disability in developed countries
• Responsible for 1/3 or more of all deaths in people over 35 years old
• The Global Burden of Disease Study in 2013
• Estimated that deaths related to cardiovascular disease has increased 41% since 1990
6
CAD in the US
CAD in Middle‐aged Men
~50%
CAD in Middle‐aged Women
~33%
7
CAD and AF
• On average, 30% of patients with AF have concomitant CAD
• 10‐15% of patients with stable CAD have an indication for long‐term oral anticoagulation
• Little is known about AF prognosis in stable CAD outpatients
• AF + CHADS2 score of 3: 4.6% annual risk of stroke Schurtz G, Bauters C, Ducrocq G, et al. Panminerva Medica 2016 December;58(4):271‐85.
8
Audience Response Question
• Which of the following is NOT a risk factor for CAD? 1.
2.
3.
4.
5.
Hypertension
Depression
Obesity
Diabetes
All of the above are risk factors for CAD
9
Risk Factors
Non‐Modifiable
Modifiable
Increasing Age: Hyperlipidemia
Men >45yrs
Low HDL
Post‐menopausal Women
High LDL
High Triglycerides
Male Sex
Tobacco Smoke
Family History Hypertension
Race African Americans
Mexican Americans
American Indians
Hawaiian
Asian Americans
Physical Inactivity
Overweight / Obesity
Diabetes Mellitus
Excessive Alcohol
Depression / Stress
10
Bleeding Risk
H
A
S
B
L
E
D
Clinical characteristic*
Points
Hypertension (ie, uncontrolled blood 1
pressure)
Abnormal renal and liver function (1 point 1 or 2
each)
Stroke
1
Bleeding tendency or predisposition
1
Labile INRs (for patients taking warfarin)
1
Elderly (age greater than 65 years)
1
Drugs (concomitant aspirin or NSAIDs) or 1 or 2
excess alcohol use (1 point each)
• Other contributing factors
• Anemia
• Hx of GI bleed
• Recent bleed
• Diabetes mellitus
• Inherited disorders
HAS‐BLED Score Total
Bleeds per 100 patient‐
years
0
1.13
1
2
3
1.02
1.88
3.74
4
8.7
5 to 9
Insufficient data
11
Etiology
12
Image from: http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad
Etiology
13
Image from: http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad
Etiology
14
Image from: http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad
Etiology
15
Image from: http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad
Etiology
16
Image from: http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad
Pathophysiology
Rupture of the vulnerable plaque Complex inflammatory and coagulation cascade
17
Image from: https://www.researchgate.net/profile/Salvatore_Cito/publication/233
973730/figure/fig1/AS:300049700540419@1448548831866/Fig‐1‐
Illustration‐of‐the‐blood‐clotting‐process‐showing‐the‐four‐main‐
steps‐of.png
Primary Hemostasis
Clopidogrel
Prasugrel
Ticlopidine
(irreversible)
Aspirin
Ticagrelor
(reversible)
Image from: https://www.researchgate.net/profile/Salvatore_Cito/publication/233
973730/figure/fig1/AS:300049700540419@1448548831866/Fig‐1‐
Illustration‐of‐the‐blood‐clotting‐process‐showing‐the‐four‐main‐
steps‐of.png
18
Clotting Cascade
Kininogen Kallikrein
Trauma
Trauma
19
Cross‐linked Fibrin Clot
Clotting Cascade
Kininogen Kallikrein
Trauma
Warfarin
Trauma
Warfarin
Rivaroxaban
Apixaban
Edoxaban
Dabigatran
20
Cross‐linked Fibrin Clot
ASPIRIN FOR SECONDARY PREVENTION OF CAD
Per ACCP Guidelines
21
CHEST Guideline Evidence
Aspirin ‐ Table 3
22
“The number of vascular events and total deaths prevented is far greater than the number of bleeding events that resulted from aspirin.”
23
CHEST Guideline Evidence
Clopidogrel ‐ Table 4
24
“After a mean follow‐up of 1.9 years, clopidogrel was associated with a possible reduction in nonfatal MI and nonfatal extracranial bleeding and little or no effect on total mortality.”
25
CHEST Guidelines Recommendation
• Long‐term single APT with aspirin (75‐100mg) OR clopidogrel 75mg daily for patients with stable CAD
• Considering difference in cost and mortality benefits, many patients are placed on daily aspirin 81mg
• Clopidogrel reasonable alternative for patients with ASA allergy
ASA 81mg, EC
CLOPIDOGREL 75mg
AWP
(120 tabs) $6.40
(90 tabs) $626.40
VA price
(120 tabs) $0.60
(90 tabs) $7.74
26
DOACS AND ASPIRIN
Evaluating Their Role in Patients with Both AF and CAD
27
CHEST Guidelines on DOACs and ASA
• Mostly discusses ASA + VKAs
• RE‐LY trial • Rates of major bleeding were roughly 2x higher for patients receiving aspirin in conjunction with either warfarin (INR 2‐3) or dabigatran
• Recommendation
• “For patients with AF and stable CAD who choose oral anticoagulation, we suggest VKA therapy alone (INR 2‐3) rather than combination of VKA therapy and aspirin.”
28
Trials Evaluating DOACs and Antiplatelet Use
• Apixaban
• ARISTOTLE
• Dabigatran
• RE‐LY
• Edoxaban
• ENGAGE
• Rivaroxaban
• ROCKET AF
29
Apixaban vs. Warfarin with Concomitant Aspirin in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial
Alexander JH, et al. Eur Heart J. 2014;35(4):224‐32.
30
Insights from the ARISTOTLE Trial
• Objectives
• Describe the use over time and dose of concomitant aspirin in patients with AF overall and in the subgroups of patients with and without arterial vascular disease
• Evaluate the efficacy and safety of apixaban compared with warfarin in patients receiving and not receiving aspirin overall and in the subgroups of patients with and without arterial vascular disease
31
Insights from the ARISTOTLE Trial
Design
• Double blind, double dummy RCT of 18201 patients with AF and at least one additional risk factor for stroke or systemic embolism
• >=75yrs, HTN, diabetes, HF, or reduced ventricular systolic function, and prior stroke or systemic embolism
Treatment Groups • Apixaban 5mg BID + warfarin placebo (N=9120) – Dose adjusted to 2.5mg BID where appropriate
• Apixaban placebo + warfarin (N=9081) with INR of 2‐3
Aspirin Users
• Defined as those using aspirin on Day 1
• Considered to be taking aspirin in a particular week if they received aspirin for at least 50% of the days of the week
32
Subgroup Breakdown
Apixaban
Warfarin
ASA added
N= 2233
N= 2201
No ASA
N= 6852
N=6847
33
Baseline Characteristics
Baseline Characteristics
Age, median (25th, 75th)
Male Sex (%)
Diabetes (%)
HTN (%)
Hx of CAD (%)
Hx of MI (%)
Hx of PCI (%)
>12 months from most recent PCI
Proportion with Stent Placed (%)
Hx of CABG (%)
Hx of Stroke (%)
CHADS2 Score
1
2
3
Aspirin Users (n=4434)
Non‐user (n=13699)
P‐value
70 (64,76)
70 (62,75)
0.0058
3029 (68.3)
1282 (28.9)
3940 (88.9)
2264 (51.1)
1046 (23.6)
744 (16.8)
8709 (63.6)
3249 (23.7)
11914 (87.0)
4354 (31.8)
1529 (11.2)
903 (6.6)
<0.0001
<0.0001
0.001
<0.0001
<0.0001
<0.0001
618 (83.4)
706 (78.5)
0.0452
518 (70.7)
562 (63.4)
0.0019
582 (13.1)
501 (11.3)
620 (4.5)
1624 (11.9)
<0.0001
0.3172
1391 (31.4)
1616 (36.4)
1472 (32.2)
4763 (34.8)
4882 (35.6)
4054 (29.2)
<0.0001
Aspirin users were more likely to be male, have diabetes, HTN, have a Hx of CAD, MI, PCI, CABG and have higher CHADS2 scores
34
Results
Reduction in Ischemic Events: Apixaban vs. Warfarin
Stroke or Systemic Embolism
Ischemic Stroke
MI
Death
ASA Status
HR
CI
ASA
0.59
0.40‐0.87
without ASA
0.85
0.67‐1.08
ASA
0.72
0.45‐1.88
without ASA
ASA
without ASA
ASA
without ASA
0.99
1.15
0.77
1.03
0.85
0.74‐1.32
0.70‐1.88
0.51‐1.14
0.72‐1.46
0.70‐1.03
Interaction P‐
value
0.1114
0.2685
0.2144
0.3727
Patients on ASA had statistically significant improvements in SSE
35
Results (cont.)
Statistically Significant
Reductions in Bleeding: Apixaban vs. Warfarin
ASA Status
HR
CI
ASA
0.77
0.6‐0.99
without ASA
0.65
0.55‐0.78
ASA
Hemorrhagic Stroke
without ASA
0.43
0.21‐0.87
0.53
0.32‐0.87
0.73
0.6‐0.89
Major Bleeding
Major or CRNM Bleeding
Any Bleeding
ASA
without ASA
0.67
0.59‐0.76
ASA
0.69
0.62‐0.77
without ASA
0.72
0.68‐0.77
Interaction P‐
value
0.29
0.6332
0.4623
0.4857
Compared to non‐users, ASA users had similar rates of bleeding 36
Authors’ Conclusions
• If there is a strong indication for combination aspirin and oral anticoagulation, apixaban seems to be safer than warfarin in patients with AF irrespective of ASA use
• In ARISTOTLE, concomitant aspirin was used in 20‐
25% of patients with AF treated with an anticoagulant (apixaban or warfarin) and was associated with a higher risk of bleeding
37
Authors’ Conclusions (cont.)
• Similar effects of apixaban, compared with warfarin, on stroke or systemic embolism, major bleeding, or mortality irrespective of concomitant aspirin use
• Adequately powered RCT are needed to better define optimal antithrombotic regimen and its duration in patients with both AF and atherosclerotic CAD, especially those with ACS or recent stenting
38
Critical Appraisal Strengths
Limitations
• One of very few trials looking at • Patients receiving ASA were different, with higher risk for the effects of concomitant aspirin and DOAC use
both ischemic and bleeding
• Large sample size
events
• Though adjustments for • Conclusions matched data confounders were made, more presented
• Clinically useful likely exist
• Aspirin use was not blinded
• Subgroup analysis‐ limited power
• Generalizability
• Bristol‐Myers Squibb and Pfizer participated in trial design and data collection
Conclusion: Apixaban + ASA still carries improved bleeding risk over warfarin +/‐ ASA and may have benefits on SSE
39
Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long‐Term Anticoagulation Therapy (RE‐LY) Trial
Dans AL, et al. Circulation. 2013;127(5):634‐40.
40
Insights from the RE‐LY Trial
• Objective
• Determine the efficacy and safety of two doses of dabigatran versus warfarin in relation to whether concomitant antiplatelet treatment was used during the RE‐LY study
41
Insights from the RE‐LY Trial
Design
Treatment Groups Antiplatelet Users
• 18,113 patients with AF and additional risk factors for stroke recruited to receive one of two blinded doses of dabigatran (110mg BID or 150mg BID) or open‐label warfarin (INR 2‐3)
• Main efficacy outcome = stroke or systemic embolism
• Safety outcome = major bleeding
•
•
•
•
Dabigatran 110mg BID
Dabigatran 150mg BID
Warfarin (INR2‐3)
+/‐ antiplatelet agent
• Use of anti‐platelet agents was allowed at the discretion of the attending physicians and recorded at every visit
• Aspirin or clopidogrel
42
Subgroup Breakdown
Dabigatran 110mg Dabigatran 150mg Warfarin (INR 2‐3)
BID
BID
Antiplatelet
Therapy
N=2322
N=2304
N=2326
No Antiplatelet Agent
N=3693
N=3772
N=3696
43
Antiplatelet Use
Antiplatelet Use in RE‐LY
• Only 27% of patients were on concomitant antiplatelet therapy at any one time during the study
No APT
Aspirin
32%
62%
ASA Dose
N
%
Clopidogrel
2%
<100mg
2908
100‐
299mg
1621
≥300mg
293
16%
8.9%
Both Aspirin and Clopidogrel
4%
1.6%
44
Baseline Characteristics
ASA users and non‐users were seemingly well balanced. No p values provided for statistically significant differences 45
Results
}
Benefits attenuated with ASA use
46
Results (cont.) CHEST: “Rates of major bleeding were roughly 2x higher for patients receiving aspirin in conjunction with either warfarin (INR 2‐3) or dabigatran”
47
Authors’ Conclusions
• Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE‐LY without affecting the advantages of dabigatran over warfarin
• Dabigatran 150mg BID reduced the primary outcome of stroke and systemic embolism compared to warfarin
• However, this effect seemed attenuated among patients who used anti‐platelets (HR 0.80, 95% CI 0.59‐1.08) in comparison to those who did not (HR 0.52, 95% CI 0.38‐0.72)
48
Critical Appraisal Strengths
Limitations
• One of very few trials looking at the effects of concomitant aspirin and DOAC use
• Large sample size
• Conclusions matched data presented
• Aspirin doses defined
• Mean duration of use was 66% of total study duration – similar to real adherence rates
• Patients receiving APT were different, with higher risk for both ischemic and bleeding events
• Though adjustments for confounders were made, more likely exist
• Aspirin and Clopidogrel used, not randomized
• Only 16% of Aspirin users used 81mg
• Subgroup analysis‐ limited power
• Generalizability
Conclusion: Dabigatran + ASA increases major bleeding risk similar to warfarin + ASA but may NOT exhibit benefits on SSE
49
Concomitant Use of Single Antiplatelet Therapy with Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF‐TIMI48 Trial
Xu H, Ruff CT, Giugliano RP, et al. J Am Heart Assoc. 2016;5(2)
50
Insights from the ENGAGE Trial
• Objective
• Study the concomitant use of SAPT on the efficacy and safety of the anti‐Xa agent edoxaban in patients with atrial fibrillation
51
Insights from the ENGAGE trial
Design
• Multinational, double‐blind, RCT comparing two dosing regimens of edoxaban with warfarin
• 21,105 patients with AF and a CHADS2 score ≥2 enrolled
• Exclusion Criteria: CrCl <30 mL/min, high bleeding risk, receiving or anticipated DAPT, Hx of stroke, ACS or coronary revascularization within 30 days of randomization
• Primary efficacy endpoint: SSE
• Primary safety endpoint: major bleeding
• Net clinical outcome: composite of SSE, all‐cause death, or major bleeding
Treatment Groups • HDER: Edoxaban 60mg/day
• ▼Edoxaban 30mg/day, if expected increased DE
• LDER: Edoxaban 30mg/day
• ▼Edoxaban 15mg/day, if expected increased DE
• Warfarin (INR2‐3)
• +/‐ ASA beginning 3 months after randomization
Antiplatelet Users
• Physician discretion
• Aspirin ≤ 100mg daily strongly encouraged
• Clopidogrel used in small subset of patients
52
Subgroup Breakdown
HDER
LDER
Warfarin (INR 2‐3)
Antiplatelet
Therapy at 3 Months
N=1642
N=1625
N=1645
No Antiplatelet Agent at 3 Months
N=4953
N=5046
N=4998
53
Antiplatelet Use
• 24.6% of patients were on concomitant antiplatelet therapy during the study, after the 3‐month point
• 25% of patients on APT at randomization discontinued within 3 months
• 1196 subjects with death/SSE/major bleed prior to 3 months OR missing APT data at 3 months were excluded
Antiplatelet Use in ENGAGE
Aspirin
23%
Clopidogrel
2%
No APT
75%
54
Baseline Characteristics
55
Results ‐ HDER 56
Results – HDER (cont.)
57
Authors’ Conclusions
• Patients with AF who were selected by their physicians to receive APT in addition to an anticoagulant had similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT
• Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT
• Patients with AF who are deemed to require the addition of a SAPT should receive a Xa inhibitor for anticoagulation whenever possible
58
Critical Appraisal Strengths
Limitations
• One of very few trials looking at the effects of concomitant aspirin and DOAC use
• Large sample size
• Consistent 24‐25% of patients were on APT throughout the study
• Very little other APT used other than ASA ≤ 100mg
• Patients receiving APT were different, with higher risk for both ischemic and bleeding events
• Though adjustments for confounders were made, more likely exist
• APT use not randomized
• 25% of patients on APT at study randomization discontinued within first 3 months
• Subgroup analysis‐ limited power
• Generalizability
• Daiichi Sankyo funded the trial, provided the study drug, and some authors are Daiichi Sankyo employees
Conclusion: Edoxaban + ASA has favorable bleeding risk over warfarin +/‐ ASA and may exhibit benefits on SSE
59
Use of Concomitant Aspirin In Patients With Atrial Fibrillation: Findings From the ROCKET AF Trial
• Shah R, Hellkamp A, Lokhnygina Y, et al. Am Heart J. 2016;179:77‐86.
60
Insights from the ROCKET AF Trial
• Objective
• Understand the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known CAD.
61
Insights from the ROCKET AF Trial
Design
Treatment Groups Antiplatelet Users
• Multicenter, double‐blind, double‐dummy, event‐
driven trial to assess non‐inferiority of rivaroxaban vs. warfarin
• Exclusion Criteria: CrCl <30 mL/min, bleeding risk, recent stroke or SEE, prosthetic heart valves, or had significant mitral stenosis
• Primary efficacy endpoint: stroke or non‐central nervous system embolism
• Secondary efficacy endpoints: MI, vascular death, and all‐cause death
• Primary safety endpoint: major or non‐major clinically relevant bleeding
• Secondary safety endpoints of major fatal bleeding, intracranial hemorrhage and hemorrhagic stroke
• Rivaroxaban 20mg daily (15mg daily if CrCl 30‐
49mL/min)
• Warfarin (INR 2‐3)
• +/‐ ASA at baseline
62
• Analysis performed using baseline aspirin use
Antiplatelet Use
63
• Mean baseline daily dose of aspirin was 99.2mg
Baseline Characteristics
ASA patients were more likely to be
‐ Female
‐ Slightly younger
‐ Paroxysmal AF
‐ Mean CHADS2 score of 3.5
‐ CAD
‐ HTN
‐ Prior MI
‐ CHF and COPD
‐ Prior VKA use
‐ ACE/ARB at baseline
‐ Digoxin at baseline
64
Statistical Methods
• Chi‐square test for categorical variables
• Presented using percentage (count)
• Wilcoxon rank‐sum test for continuous variables
• Presented using median (2th‐75th percentiles)
• Cox proportional hazard method used to calculate hazard ratios
• All endpoints were generated as events per 100 patient‐years and total events
65
Results
66
Results (cont.)
67
Results (cont.)
68
Authors’Conclusions
• Aspirin use at baseline was associated with an increased risk of bleeding and all‐cause death in ROCKET AF, a risk most pronounced in patients without known CAD
• No significant differences in treatment effect for rivaroxaban or warfarin were detected between patients with and without baseline aspirin use for any of the efficacy outcomes or the safety outcomes
• Baseline ASA + Rivaroxaban vs Baseline ASA + Warfarin was significant for reducing all‐cause death and less intracranial and fatal bleeds
69
Critical Appraisal Strengths
Limitations
• One of very few trials looking at • Post‐hoc analysis
the effects of concomitant aspirin • Study not powered to show a and DOAC use
difference
• Author’s conclusions
• Large sample size
• ASA not randomized, started and stopped during the trial
• Generalizability – high baseline CHADS2 score – almost 3.5
• Jansen grant funded the study
Conclusion: Rivaroxaban + ASA may have favorable benefits for CAD secondary prevention and may have less bleeding events than warfarin + ASA. More data needed.
70
Summary
• Apixaban
• Apixaban + ASA still carries improved bleeding risk over warfarin +/‐ ASA and may have benefits on SSE
• Dabigatran
• Dabigatran + ASA increases major bleeding risk similar to warfarin + ASA but may NOT exhibit benefits on SSE
• Edoxaban
• Edoxaban + ASA has favorable bleeding risk over warfarin +/‐ ASA and may exhibit benefits on SSE
• Rivaroxaban
• Conclusion: Rivaroxaban + ASA may have favorable benefits for CAD secondary prevention and may have less bleeding events than warfarin + ASA. More data needed.
71
Overall Conclusions
• ASA 81mg + DOAC therapy (apixaban, edoxaban) has so far been shown to be consistently safer in regards to bleeding events than warfarin therapy +/‐ ASA therapy
• Use of ASA with dabigatran 150mg BID may attenuate beneficial effects of ASA therapy while still carrying an increased risk of bleeding
• More data are needed to make recommendations on rivaroxaban’s place in AF + CAD management
72
Clinical Recommendations
• Careful consideration should be made when recommending ASA + DOAC therapy
• Increases bleeding risk from baseline, regardless of DOAC chosen
• May have benefits on overall SSE
• Monotherapy with a DOAC is likely best for most patients
• CHEST Guideline recommendation
• If your patient has AF and a strong clinical indication for secondary CAD event prevention, recommend edoxaban or apixaban as preferred DOAC options
• Not enough data to conclude rivaroxaban’s role
• Dabigatran may have attenuated SSE benefits with concomitant APT and still carries increased bleeding risk similar to warfarin + ASA
73
Should It Stay or Should It Go?
Aspirin Therapy for Patients with Stable CAD Post‐MI/TIA with Atrial Fibrillation on Concurrent DOAC Therapy
Erin R. Pilcher, Pharm.D.
PGY1 Pharmacy Practice Resident
Central Texas Veterans Healthcare System
01/06/2017
74
Acknowledgements
• Dr. Erin Pilcher would like to thank the following people for their assistance and guidance in this presentation: • Dr. Christine Wicke, Pharm.D., BCACP, CDE
• Dr. Katerine Getchell, Pharm.D., BCACP • My Co‐Residents:
• Dr. Sarah Cho
• Dr. Diana Loffgren
• Dr. Steven Braun
75
Questions
76
Email: [email protected]
Resources
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2)
3)
4)
5)
6)
7)
8)
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Alexander JH, Lopes RD, Thomas L, et al. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2014;35(4):224‐32
Behnes M, Fastner C, Ansari U and Akin I. New oral anticoagulants in coronary artery disease. Cardiovascular and Haematological Disorders‐Drug Targets. 2015(15)101‐105.
Dans AL, Connolly SJ, Wallentin L, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long‐Term Anticoagulation Therapy (RE‐LY) trial. Circulation. 2013;127(5):634‐40.
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Schurtz G, Bauters C, Ducrocq G, et al. Effect of aspirin in addition to oral anticoagulants in stable coronary artery disease outpatients with an indication for anticoagulation. Panminerva Medica 2016 December;58(4):271‐85.
Shah R, Hellkamp A, Lokhnygina Y, et al. Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial. Am Heart J. 2016;179:77‐86.
77
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