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Efficacy of ticagrelor compared to clopidogrel

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AstraZeneca has announced results from a PLATO sub-analysis in acute coronary syndromes (ACS) patients with and without extensive coronary artery disease (CAD) managed invasively or non-invasively. Results showed that ticagrelor plus aspirin, compared to clopidogrel plus aspirin, reduced cardiovascular (CV) death, myocardial infraction (MI) and stroke in ACS patients regardless of CAD extent and treatment strategy (invasively or non-invasively managed).
These findings are consistent with results from the overall PLATO study which showed a reduction in CV events with ticagrelor compared with clopidogrel, with similar risk for major bleeding. Non-coronary artery bypass grafting (CABG) and non-procedural bleeding was more common with BRILINTA. Data from this sub-analysis were presented today at the American Heart Association (AHA) Annual Meeting in Los Angeles. Ticagrelor is known as BRILIQUE in the European Union and BRILINTA elsewhere and is indicated for the treatment of ACS.
“ACS continues to be a major cause of morbidity and loss of quality of life,(1) accounting for more than 40% of all CV deaths worldwide.“(2) stated Dr Stefan James, MD PhD, Dept. of Cardiology and Uppsala Clinical Research Center, Sweden. “Given this significant disease burden, it is critical to study new, more potent treatment options for ACS patients independent of the extent of CAD, and this sub-analysis provides important insights for managing those patients at increased risk of thrombotic CV events.” 
Results of this sub-analysis showed that ticagrelor plus aspirin, compared to clopidogrel plus aspirin, statistically significantly reduced the composite endpoint (CV death, MI, and stroke) in ACS patients with extensive CAD (14.9% vs. 17.6%; hazard ratio (HR) 0.85 [0.73, 0.98]), similar to its reduction in those without extensive CAD (6.8% vs. 8.0%; HR 0.85 [0.74, 0.98]).
Major bleeding was similar with ticagrelor plus aspirin versus clopidogrel plus aspirin among patients without (7.3% vs. 6.4%; HR, 1.14 [0.98, 1.33]) and with (25.7% vs. 25.5%; HR, 1.02 [0.90, 1.15]) extensive CAD. PLATO demonstrated that with ticagrelor, there was no increase in overall major/fatal bleeding over the course of one year of treatment (11.6% for ticagrelor versus 11.2% for clopidogrel); however, non-CABG major bleeding was more common with ticagrelor versus clopidogrel (4.5% vs. 3.8).
When possible, Of the 15,388 ACS study patients for whom the extent of CAD was known, 4,644 (30%) had extensive CAD. Extensive CAD patients had more high risk characteristics at study entry and experienced more clinical events during follow-up. In this sub-analysis, fewer patients ACS with extensive CAD underwent percutaneous coronary intervention (58%) compared to those without (79%, p<0.001), and more ACS patients with extensive CAD underwent coronary artery bypass graft surgery (16% vs. 2%, p<0.001).
Coronary artery disease (CAD) develops when coronary arteries — the major blood vessels that supply the heart with blood, oxygen and nutrients — become damaged or diseased. Atherosclerosis is the main cause for CAD. When cholersterol-containing deposits (plaque) builds up, they narrow coronary arteries, causing the heart muscle to receive less blood.
Eventually, the decreased blood flow may cause chest pain (angina), shortness of breath, or other CAD signs and symptoms. An extensive or complete blockage can cause a heart attack.(3)
References
  1. Turpie, A. Burden of Disease: Medical and Economic Impact of Acute Coronary Syndromes. AJMC 2006; S431.
  2. World Health Organization. Cardiovascular Diseases. Available at: http://www.who.int/nmh/publications/fact_sheet_cardiovascular_en.pdf
  3. Mayo Clinic. Coronary Artery Disease. Available at: http://www.mayoclinic.com/health/coronary-artery-disease/DS00064


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