New Anti-Clotting Drug Beats Plavix
SUNDAY Aug. 30, 2009 -- A new anti-clotting drug, ticagrelor (Brilinta), was better than than clopidogrel (Plavix) in preventing new heart attacks and in reducing deaths among patients who have had a heart attack, a new study finds.
"Clopidogrel is widely used in the treatment of acute coronary syndrome," said lead researcher Dr. Robert A. Harrington, director of the Duke Clinical Research Institute at Duke University. "Ticagrelor looks to be a superior antiplatelet agent in patients with acute coronary syndrome."
Co-researcher Dr. Lars Wallentin, a professor of cardiology at the Uppsala Clinical Research Center at University Hospital, in Sweden, added that "now we have a new and better alternative to standard treatment to prevent patients with myocardial infarction from new myocardial infarction, and also to improve their chances of survival."
The report is published in the Aug. 30 online edition of the New England Journal of Medicine, to coincide with the planned presentation of the study Sunday at the European Society of Cardiology Congress in Barcelona.
For this phase 3 study, called PLATO (Platelet Inhibition and Patient Outcomes), 18,624 patients were randomly assigned to ticagrelor or clopidogrel. Both drugs prevent blood clotting, which could lead to another heart attack. Over 12 months, patients taking ticagrelor had fewer heart attacks and strokes compared with patients taking clopidogrel (9.8 percent versus 11.7 percent), the researchers found. Moreover, fewer patients taking ticagrelor died (4.5 percent) compared with patients taking clopidogrel (5.9 percent).
The greatest risk associated with these drugs is life-threatening bleeding, but there was no significant difference between the drugs in the risk of bleeding, the researchers noted.
However, patients taking ticagrelor were more likely to have spontaneous intracranial and gastrointestinal bleeding than people taking clopidogrel (4.5 percent versus 3.8 percent).
In addition, shortness of breath was more common in patients taking ticagrelor, compared with patients taking clopidogrel (14.2 percent versus 9.2 percent). However, only a few patients stopped treatment because of it, the study authors reported.
Wallentin noted that ticagrelor and clopidogrel work differently. "Clopidogrel has an irreversible affect on the platelets, so platelets remain inactive for up to a week. With ticagrelor, as soon as you stop the treatment the effect stays for one to two days," he said.
This difference is important for patients who need surgery where excess bleeding is a major risk, Wallentin explained.
Also, about 30 percent of patients do not respond to clopidogrel, Wallentin said. "But with the new compound, everybody has enough protection," he added.
Ticagrelor is not yet approved by the U.S. Food and Drug Administration, Harrington noted.
"Sponsor [Astra Zeneca] needs to apply for regulatory approval, but assuming approval, clinicians and patients will have an alternative to clopidogrel that appears to be associated with better cardiac clinical outcomes," he said.
Dr. Albert Schomig, from the Department of Cardiology at Deutsches Herzzentrum Munchen in Munich, Germany, and author of an accompanying journal editorial, found both strengths and weaknesses in the trial and the new drug.
"The new drug ticagrelor has interesting properties: rapid, strong and reversible antiplatelet effects," Schomig said. "It is the first time to have an oral antiplatelet drug with reversible effect suitable for chronic use in patients with acute coronary syndromes. This is a very useful property for patients who are likely to have surgery shortly," he said.
However, a few side effects such as shortness of breath, slowed heartbeat, increases in uric acid and creatinine levels in blood that appeared with ticagrelor have not been seen before with other antiplatelet drugs, Schomig said. "Therefore, ticagrelor should be used after careful exclusion of patients at higher risk of showing these side effects," he said.
On the whole, ticagrelor is a useful addition to the antiplatelet therapy, Schomig said. "We have now the opportunity to choose between three drugs, clopidogrel, prasugrel [Effient] and ticagrelor, in patients with acute coronary syndromes, taking into account the advantages and disadvantages of each one," he said.
Another expert, UCLA cardiologist Dr. Gregg C. Fonarow, said "the findings from the PLATO trial are very compelling. The significant reduction in deaths from vascular causes, myocardial infarction and stroke with ticagrelor, compared to clopidogrel, without any significant increase in fatal or life-threatening bleeding and coupled with a reduction in all-cause mortality, are very impressive."
Fonarow added, "Ticagrelor represents an important new treatment advance for the management of patients with acute coronary syndromes."
Dr. Byron Lee, a cardiologist from the University of California at San Francisco, said that "ticagrelor is known to be a more potent antiplatelet agent than clopidogrel. Therefore, we were worried about more bleeds with this new agent. However, this study convincingly shows that ticagrelor leads to better outcomes with only minimal increase in bleeding risk. I expect this new drug to get FDA approval very soon."
Another study reported in the same journal that was also scheduled to be presented Sunday at the cardiology meeting in Barcelona compared the blood thinner warfarin with a new drug, dabigatran (Pradaxa) in 18,113 patients with atrial fibrillation.
Atrial fibrillation is a common heart rhythm problem that causes the heart to beat too fast and irregularly. This, in turn, affects the pumping action of the heart and raises the risk for stroke. Patients with atrial fibrillation often take warfarin to prevent strokes. However, finding the right dose can be difficult and most patients need monthly blood tests to monitor the drug.
In this study, Canadian researchers found that dabigatran was as effective as warfarin in preventing strokes. In addition, the lower dose of dabigatran caused less bleeding than warfarin. At the higher dose, the risk of bleeding was the same for both drugs, the researchers reported.
While not yet approved for use in the United States, dabigatran has been approved in Europe to prevent clotting in people who have had hip or knee replacement surgery.
Posted: August 2009