MD Conference Express ACC 2012 - (Page 34)
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SELECTED UPDATES IN ANTIPLATELET THERAPY
The Complexities of Dual Antiplatelet Therapy
Written by Lori Alexander
Dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) is becoming more complex, making it difficult to select the optimal therapy, said Matthew J. Price MD, FACC, Scripps Clinic, La Jolla, California, USA. With several P2Y12 ADP receptor antagonists that have been approved at varying doses, as well as three different doses of aspirin that are commonly used, there are multiple different combinations of oral DAPT. The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines note the options for DAPT as clopidogrel, prasugrel, and ticagrelor but provide no guidance on the selection of a particular agent [Levine GN et al. Circulation 2011]. The optimal regimen; the potential risk for adverse events, bleeding in particular; and the role of genotyping are among the most important questions that remain unanswered. Drug Options for DAPT Clopidogrel, when combined with aspirin, leads to improved outcomes (compared with aspirin alone) for patients with ACS, regardless of whether they are undergoing percutaneous coronary intervention (PCI) or not. Despite better results, studies showed that inhibition of platelet aggregation with clopidogrel was “variable, unpredictable, and insufficient,” said Paul Gurbel, MD, FACC, Sinai Center for Thrombosis Research, Baltimore, Maryland, USA [Gurbel PA et al. Circulation. 2003]. DAPT with prasugrel achieved more rapid, potent, and consistent inhibition of platelet function than clopidogrel + aspirin. In the TRITON-TIMI 38 trial, prasugrel substantially reduced rates of ischemic events (9.9% vs 12.1%; HR, 0.81; 95% CI, 0.73 to 0.90; p<0.001), including stent thrombosis (1.1% vs 2.4%; HR, 0.48; 95% CI, 0.36 to 0.64; p<0.001), compared with clopidogrel in patients with ACS treated with coronary stenting [Wiviott SD et al. N Engl J Med 2007]. However, prasugrel increased the rate of major bleeding (2.4% vs 1.8%; HR, 1.32; 95% CI, 1.03 to 1.68; p=0.03), including fatal bleeding (0.4% vs 0.1%; HR, 4.19; 95% CI, 1.58 to 11.11; p=0.002). Overall mortality was similar for the two drugs. The most recently approved P2Y12 antagonist, ticagrelor, has a rapid onset, consistent antiplatelet effect, and is reversible [Gurbel PA et al. Circulation 2009]. Ticagrelor was compared with clopidogrel in the PLATO trial and significantly reduced the rate of the primary composite endpoint (cardiovascular [CV]-related death, myocardial infarction [MI], and stroke) by 1.9% absolute (p=0.0003), including a significant reduction in CV mortality (4.0% vs 5.1%; HR, 0.79; 95% CI, 0.69 to 0.91; p=0.001) [Wallentin L et al. N Engl J Med 2009]. The results were consistent in many subgroups including patients who were planned for an invasive strategy; those with ST-elevation myocardial infarction (STEMI), renal dysfunction and, previous stroke; and those having coronary artery bypass grafting within 5 days of treatment. Ticagrelor was of benefit independently of the loading dose of clopidogrel (300 or 600 mg) [Cannon CP et al. Lancet 2010], and also regardless of the genetic CYP2C19 polymorphism that identifies low responders to clopidogrel [Wallentin L et al. Lancet 2010]. Ticagrelor achieves a greater pharmacodynamic effect than clopidogrel, irrespective of CYP2C19 genotype [Tantry US et al. Circ Cardiovasc Genet 2010], which likely explains the higher rate of bleeding with ticagrelor compared with clopidogrel that is seen outside of the operating room. Comparisons across the trials of P2Y12 antagonists are difficult due to differences in the study designs in which the efficacy and safety of the drugs are evaluated (Table 1).
Official Highlights From the
ACC-i2
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innovation in intervention
March 24 – 27, 2012 • CHICAGO
Exhibits: March 24 – 26
34
May 2012
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Table of Contents for the Digital Edition of MD Conference Express ACC 2012
MD Conference Express ACC 2012
Table of Contents
Treatment of AMI in the Post-Herrick Era
The State of Hypertension Guidelines: 2012
ACRIN PA 4005: Coronary CTA in the ED Identifies Low-Risk Patients and Shortens Length of Stay
One-Year STAMPEDE Trial Results
TAVR Associated with Increased Late Mortality from Paravalvular Regurgitation
The CABG Surgery Off- or On- Pump- Revascularization Study (CORONARY)
The Moderate PE Treated with Thrombolysis Study (MOPETT)
Pacemaker Therapy In Patients With Neurally Mediated Syncope and Documented Asystole
Outcomes from the BRIDGE-ACS Trial
ROMICAT II: More Data Evaluating CT-First for Acute Chest Pain ED Triage
Elective PCI at Community Hospitals With Versus Without On-Site Surgery
Results from the TRA 2P-TIMI 50 Trial
The HOST-ASSURE Randomized Trial
New Monoclonal Antibody to PCSK9 Markedly Lowers LDL-C in Patients on Atorvastatin
Oral Rivaroxaban Alone for Symptomatic PE
Neutral Outcomes But Important Insights From FOCUS-CCTRN
Imaging
STEMI
Acute Coronary Syndrome
Antiplatelet Therapy
New Anti-Diabetes Agents Offer Promise in the Fight Against CVD
The New Hypertrophic Cardiomyopathy Practice Guidelines
MD Conference Express ACC 2012
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