Adapted from Rocca B et al. Expert Rev Cardiovasc Ther. 2013;11(3):365-379.

Aspirin

Is it still the bedrock

of antiplatelet therapy?

Aspirin: Secondary Prevention Trials

2009 ATTMeta‐Analysis of 16 Secondary Prevention  Trials n=17,000

Reduction in major coronary event  RR=0.80              P<.0001

Vascular mortality RR=0.91 P=NS

Reduction in total stroke  RR=0.81               P=.002

Reduction in any serious vascular event RR=0.81               P<.0001

Increase in haemorrhagic stroke RR= 1.67              P=.07

Increase in extracranial bleeding  RR=2.69               P<.05

Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, Collins R, et al. Lancet. 2009;373(9678):1849-1860.

Adapted from Gurbel PA et al. J Am Coll Cardiol. 2007;50(19):1822-1834.

ADP, Collagen, Shear, Thrombin

Tx A2

ReceptorCOX-1 Non-specificPathway

COX-1

Arachidonic Acid

TxA2

MembranePhospholipids

PlateletActivation

Receptor

Urine 11-dh-TxB2

Serum TxB2 (unstable)

AA

Aspirin acetylation site-Ser 530

Converts AA to PGG2/PGH2

Tyr 385

PGG2,PGH2

Thromboxane synthase

11-oH-dehydrogenase

Adapted from Catella-Lawson F et al. N Engl J Med. 2001;345(25):1809-1817.

Aspirin: Secondary Prevention Trials

2009 ATTMeta‐Analysis of 16 Secondary Prevention  Trials n=17,000

Reduction in major coronary event  RR=0.80              p<0.0001

Vascular mortality RR=0.91 p=NS

Reduction in total stroke  RR=0.81               p=0.002

Reduction in any serious vascular event RR=0.81               p<0.0001

Increase in haemorrhagic stroke RR= 1.67              p=0.07

Increase in extracranial bleeding  RR=2.69               p<0.05

Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, Collins R, et al. Lancet. 2009;373(9678):1849-1860.

Adapted from Halvorsen S et al. J Am Coll Cardiol. 2014;64(3):319-327.

A Systematic Review–

“ In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), 

followed by 325 mg/d (35%).” 

“Currently available clinical data do not support the routine, long‐term use of aspirin dosages 

greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, 

which may be commonly prescribed, do not better prevent events but are associated with 

increased risks of gastrointestinal bleeding.“ 

– Campbell CL et al. JAMA. 2007;297(18):2018-2024.

CHARISMA Trial–

“Daily aspirin doses of 100 mg or greater were associated with no clear benefit in patients taking 

aspirin only and possibly with harm in patients taking clopidogrel. Daily doses of 75 to 81 mg 

may optimize efficacy and safety for patients requiring aspirin for long‐term prevention, 

especially for those receiving dual antiplatelet therapy.”

– Steinhubl SR et al. Ann Intern Med. 2009;150(6):379-386.

Recommended for secondary CV event prevention in ACS—European, US, and Canadian guidelines

Additional recommendations—post‐stent placement, post‐CABG, PAD, ischemic stroke

Task Force members, Windecker S, et al. Eur Heart J. 2014;35(37):2541-2619; Amsterdam EA et al; ACC/AHA Task Force Members. Circulation. 2014;130(25):2354-2394; Tanguay JF et al; Canadian Cardiovascular Society. Can J Cardiol. 2013. 2013;29(11):1334-1345.

US Food and Drug Administration. Drug Safety and Availability. www.fda.gov/drugs/drugsafety. Accessed September 24, 2015.

Ibuprofen can interfere with the antiplatelet effect of low‐dose aspirin

Recommended for secondary CV event prevention in ACS—European, US, and Canadian guidelines

Additional recommendations—post‐stent placement, post‐CABG, PAD, ischemic stroke

Task Force members, Windecker S, et al. Eur Heart J. 2014;35(37):2541-2619; Amsterdam EA et al; ACC/AHA Task Force Members. Circulation. 2014;130(25):2354-2394; Tanguay JF et al; Canadian Cardiovascular Society. Can J Cardiol. 2013. 2013;29(11):1334-1345.

“There was no clinically meaningful interaction of aspirin 

with prasugrel, suggesting that 

previous observations with potent antiplatelet agents indicating differential results are not universal.”

Reprinted from Journal of the American College of Cardiology. 63(3):225-232. Kohli P et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38). Copyright 2014, with permission from Elsevier.

ASA +CLP

ASA

ASAASA +CLP

CURE, CREDO, CLARITY, COMMIT, and CHARISMA Trials

ASA +CLP

2.7

3.3

2

2.3

2.6

2.9

3.2

3.5

%

MIOR=0.82; P<.0001

ASA +CLP

ASA6.3

6.7

6.1

6.2

6.3

6.4

6.5

6.6

6.7

6.8

%

Mortality OR=0.94; P=.026

ASA1.2

1.4

1

1.3

1.6

1.9

%

StrokeOR=0.82; P=.002

Helton TJ et al. Am J Cardiovasc Drugs. 2007(4);7:289-297.

1.6

1.3

0.28 0.27

0

0.4

0.8

1.2

1.6

2Major Bleeding

OR=1.26; P<.0001

Fatal BleedingOR=1.04; P=.79

ASA

ASA +CLP

Clopidogrel HR 95% CI P P int’n

Standard Double

CV Death/MI/Stroke (Overall)

ASA High 4.6 3.8 0.83 0.70-0.99 .036.043

ASA Low 4.2 4.5 1.07 0.91-1.27 .42

MI/Stent Thrombosis (PCI pts)

ASA High 3.8 2.7 0.71 0.56-0.90 .005 .19

ASA Low 3.6 3.2 0.89 0.71-1.12 .32

Major Bleed (Overall)

ASA High 2.2 2.4 1.08 0.86-1.37 .51.099

ASA Low 1.9 2.7 1.43 1.13-1.81 .003

CURRENT‐OASIS 7 Investigators, Mehta SR et al. N Engl J Med. 2010;363(10):930‐942.

Adapted from Peters RJ et al; Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial Investigators. Circulation. 2003;108(14):1682-1687.

“There was no clinically meaningful interaction of aspirin 

with prasugrel, suggesting that 

previous observations with potent antiplatelet agents indicating differential results are not universal.”

Reprinted from Journal of the American College of Cardiology. 63(3):225-232. Kohli P et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38). Copyright 2014, with permission from Elsevier.

Primary Efficacy Outcome (CV death, MI or stroke)

Primary Safety Outcome (protocol defined major bleeding)

Adapted from Wallentin L. N Engl J Med. 2009;361(11):1045-1057. Supplementary Appendix. http://www.nejm.org/doi/suppl/10.1056/NEJMoa0904327/suppl_file/nejm_wallentin_1045sa1.pdf. Accessed September 29, 2015.

Primary Efficacy Outcome (CV death, MI, or stroke)

Adapted from Mahaffey KW et al; PLATO Investigators. Circulation. 2011;124(5):544-554.

Primary Efficacy Outcome (CV death, MI, or stroke)

Primary Outcome Measures: MI or stroke

81 mg Aspirin

Duration = up to 30 months

325 mg Aspirin

Patients after MI or with significant coronary artery stenosis

n=20,000

Patient-Centered Outcomes Research Institute (PCORI). http://www.pcori.org/research-results/2015/aspirin-dosing-patient-centric-trial-assessing-benefits-and-long-term. Accessed September 25, 2015.

Should be a lifelong therapy for secondary CV event prevention

Several ongoing trials for secondary prevention in AF, CAD, and PAD, including PIONEER AF‐PCI, RE‐DUAL, PCI, GLOBAL LEADERS, TWILIGHT, COMPASS

Adapted from Capodanno D et al. Circ Cardiovasc Interv. 2011;4(2):180-187.

Each ER capsule  contains a core of release‐rate–limiting, film‐coated microcapsules containing 162.5 mg of ASA. 

Characteristic diffusion‐based dissolution profile

Reprinted by permission of Future Medicine Ltd. Bliden KP et al. Future Cardiol. 2015 Sep 10. [Epub ahead of print]

Primary Outcome Measures: MI or stroke

81 mg Aspirin

Duration = up to 30 months

325 mg Aspirin

Patients after MI or with significant coronary artery stenosis

n=20,000

Patient-Centered Outcomes Research Institute (PCORI). http://www.pcori.org/research-results/2015/aspirin-dosing-patient-centric-trial-assessing-benefits-and-long-term. Accessed September 25, 2015.

Should be a lifelong therapy for secondary CV event prevention

Several ongoing trials for secondary prevention in AF, CAD, and PAD, including PIONEER AF‐PCI, RE‐DUAL, PCI, GLOBAL LEADERS, TWILIGHT, COMPASS

Adapted from Capodanno D et al. Circ Cardiovasc Interv. 2011;4(2):180-187.

Inhibition of serum TxB2 production after single doses of ER‐ASA 20–325 mg

Inhibition of serum TxB2 production after single doses of IR‐ASA 5‐81 mg

Patrick J et al. Postgrad Med. 2015;127(6):573–580.

Phase I, open‐label, 4‐way, randomized, crossover, dose response study in healthy volunteers

Reprinted by permission of Taylor & Francis Ltd. Patrick J, Dillaha L, Armas D, Sessa WC. A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation. Postgraduate Medical Journal. August 2015, Taylor & Francis.

32 studies examining long‐term use of aspirin 

>144,800 patients

Poor compliance with low‐dose aspirin therapy ranged from 10% to more than 50%

Patient‐initiated discontinuation of therapy—30%

Common predictors in both categories were:• Lower education level• Female sex• History of depression, diabetes mellitus, or cigarette smoking  

Herlitz J et al. Am J Cardiovasc Drugs. 2010;10(2):125-141.

Platelet Aspirin Resistance Is Rare in Compliant Patients With Coronary Artery Disease

Tantry US et al. J Am Coll Cardiol. 2005;46 (9):1705-1709.

Adapted from Biondi-Zoccai G et al. Int J Cardiol. 2015;182:148-154.

Sex and race independently influence platelet‐fibrin clot strength

Black women appear to have the highest thrombogenicity profile, potentially conferring a high‐risk phenotype for thrombotic event occurrence

Lev El et al. J Am Heart Assoc. 2014;3(5):e001167.

Continuation of aspirin, once thienopyridine is discontinued after stent implantation, is supported 

Aspirin therapy is recommended indefinitely after CABG to reduce graft occlusion—ACC/AHA recommendation 

If undergoing surgery, aspirin should not be discontinued unless surgery is a neurosurgical procedure 

Kimura T et al; j-Cypher Registry Investigators. Circulation. 2009;119(7):987-995; Kulik A et al. Circulation. 2015;131(10):927-964.