Dual antiplatelet therapy is the cornerstone in the management of patients with acute
coronary syndromes (ACS). Ticagrelor, an oral, direct, reversibly binding, P2Y12 receptor antagonist, is approved for the prevention of atherothrombotic events in
adult patients with ACS. In the PLATelet inhibition and patient Outcomes (PLATO) trial,
ticagrelor was associated with significant reductions in cardiovascular events, cardiovascular
mortality, and all-cause mortality compared with clopidogrel. A subanalysis of PLATO
trial data identified a geographic region interaction (p = 0.045), indicating reduced
efficacy of ticagrelor versus clopidogrel in North American patients. This effect
could be due to chance, but may be explained by an interaction of ticagrelor with
high aspirin doses, which are commonly used in the United States. In patients taking
low-dose maintenance aspirin, ticagrelor was more effective than clopidogrel in decreasing
cardiovascular events regardless of the geographic region. A proposed hypothetical
mechanism for the interaction between ticagrelor and higher aspirin dose is linked
to the level of P2Y12 inhibition and the potential prothrombotic effects of high-dose aspirin through the
suppression of prostacyclin. A review of data regarding aspirin use for secondary
prevention of events in ACS demonstrated that low aspirin doses (75 to 160 mg/day)
are consistently favored for short- and long-term use because of the lack of a dose-response
relationship between increasing aspirin dose and improved efficacy, and a higher incidence
of gastrointestinal bleeding with increasing aspirin dose. The use of low aspirin
doses reflects good clinical practice and is encouraged in current guidelines.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Heart disease and stroke statistics–2011 update: a report from the American Heart Association.Circulation. 2011; 123: e18-e209
- Platelet activation and atherothrombosis.N Engl J Med. 2007; 357: 2482-2494
- Antiplatelet drugs: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: e89S-e119S
- Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: e637S-e668S
- ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).Eur Heart J. 2011; 32: 2999-3054
- 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non–ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.J Am Coll Cardiol. 2012; 60: 645-681
- Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology.Eur Heart J. 2008; 29: 2909-2945
- 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.Circulation. 2009; 120: 2271-2306
- Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: 7S-47S
- Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006.JAMA. 2007; 297: 1892-1900
- The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.J Clin Invest. 1975; 56: 624-632
- Low-dose aspirin for the prevention of atherothrombosis.N Engl J Med. 2005; 353: 2373-2383
- Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.Lancet. 1988; 2: 349-360
- Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860
- A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease.Eur Heart J. 2006; 27: 2667-2674
- Seeking the optimal aspirin dose in acute coronary syndromes.Am J Cardiol. 2002; 90: 622-625
- Aspirin dose for the prevention of cardiovascular disease: a systematic review.JAMA. 2007; 297: 2018-2024
- Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).Chest. 2008; 133: 199S-233S
- P2Y12, a new platelet ADP receptor, target of clopidogrel.Semin Vasc Med. 2003; 3: 113-122
- Prasugrel.Circulation. 2010; 122: 394-403
- The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin.Drug Metab Dispos. 2003; 31: 53-59
Plavix (clopidogrel) prescribing information. Available at: http://products.sanofi.us/plavix/plavix.html (last accessed March 14, 2012).
Plavix (clopidogrel) summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000174/WC500042189.pdf (last accessed March 14, 2012).
- Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.N Engl J Med. 2001; 345: 494-502
- Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study.Circulation. 2003; 108: 1682-1687
- Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.N Engl J Med. 2005; 352: 1179-1189
- Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.Lancet. 2005; 366: 1607-1621
- Prasugrel versus clopidogrel in patients with acute coronary syndromes.N Engl J Med. 2007; 357: 2001-2015
Effient (prasugrel) prescribing information. Available at: http://pi.lilly.com/us/effient.pdf (last accessed March 14, 2012).
Effient (prasugrel) summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000984/WC500021971.pdf (last accessed March 14, 2012).
Eli Lilly and Company. Cardiovascular and Renal Drugs Advisory Committee briefing document. Effient (Prasugrel). Acute coronary syndromes managed by percutaneous coronary intervention. Available at: http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4412b1-03-Lilly.pdf (last accessed October 12, 2012).
- Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation.J Thromb Haemost. 2009; 7: 1556-1565
- Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist.Cardiovasc Ther. 2009; 27: 259-274
Brilinta (ticagrelor) prescribing information. Available at: http://www1.astrazeneca-us.com/pi/brilinta.pdf (last accessed March 13, 2012).
Brilique (ticagrelor) summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001241/WC500100494.pdf (last accessed March 13, 2012).
- Ticagrelor versus clopidogrel in patients with acute coronary syndromes.N Engl J Med. 2009; 361: 1045-1057
- Ticagrelor compared with clopidogrel by geographic region in the platelet inhibition and patient outcomes (PLATO) trial.Circulation. 2011; 124: 544-554
- Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial.Am Heart J. 2009; 157: 599-605
- Secondary prevention of vascular disease by prolonged antiplatelet treatment.Br Med J (Clin Res Ed). 1988; 296: 320-331
- The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials.Br J Clin Pharmacol. 1993; 35: 219-226
- Collaborative overview of randomised trials of antiplatelet therapy–I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.BMJ. 1994; 308: 81-106
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.BMJ. 2002; 324: 71-86
- ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.Circulation. 2008; 118: 1894-1909
- Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury.Ann Intern Med. 1994; 120: 184-189
- Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.N Engl J Med. 2010; 363: 930-942
- Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy.Circulation. 2008; 117: 192-199
- Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects.J Clin Invest. 1982; 69: 1366-1372
- Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials.Am Heart J. 2011; 162: 115-124
- Aspirin.Circulation. 2000; 101: 1206-1218
- Patterns of aspirin dosing in non-ST-elevation acute coronary syndromes in the CRUSADE Quality Improvement Initiative.Am J Cardiol. 2007; 99: 1496-1499
- Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study.Eur Heart J. 2009; 30: 900-907
AstraZeneca. Ticagrelor NDA 22-433 briefing document for cardiovascular and renal drug advisory committee meeting. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/cardiovascularandrenaldrugsadvisorycommittee/ucm220197.pdf (last accessed October 12, 2012).
- Anti-platelet therapy: cyclooxygenase inhibition and the use of aspirin with particular regard to dual anti-platelet therapy.Br J Clin Pharmacol. 2011; 72: 619-633
- Anti-platelet effects of aspirin vary with level of P2Y(12) receptor blockade supplied by either ticagrelor or prasugrel.J Thromb Haemost. 2011; 9: 2103-2105
- Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs after acute myocardial infarction.Circulation. 2006; 113: 2906-2913
- In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation.J Thromb Haemost. 2011; 9: 552-561
- 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2011; 123: 2022-2060
- ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction).J Am Coll Cardiol. 2004; 44: E1-E211
Article Info
Publication History
Published online: June 10, 2013
Accepted:
April 17,
2013
Received in revised form:
April 17,
2013
Received:
January 9,
2013
Footnotes
The author did not receive any financial compensation for authoring this article. Medical writing support was funded by AstraZeneca .
See page 743 for disclosure information.
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
