An article Online First and in an upcoming edition of The Lancet reports the new analysis of the PLATO trial (PLATelet inhibition and patient Outcomes). New research shows that the stronger anticlotting medication tricagrelor reduces death rates without increasing bleeding compared with the current standard treatment of clopidogrel for heart attack patients. The article is the work of Dr Christopher P Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA, USA, and colleagues.
Dr Cannon explains: “Heart attacks are caused by blood clots in the heart artery. We see today that using a stronger anticlotting drug lowered the chance of having a second heart attack – and reduced the risk of dying from one. This is a key advance for heart attack patients.” An associated note qualifies the introduction of ticagrelor as ‘a landmark event that should redefine the care of patients with acute coronary syndromes’.
Clopidogrel is an antiplatelet drug. It is used in combination with aspirin in patients with acute coronary syndrome (heart attack/unstable angina). It prevents clots forming and reduces the risk of further heart attacks, stroke, and death. Ticagrelor has a superior and more consistent antiplatelet effect than does clopidogrel. In addition, it has a faster onset and offset of action. The authors compared in this study the two drugs in patients with acute coronary syndromes who were planned to undergo invasive procedures. Those procedures included angioplasty and stenting of the coronary artery.
Of a total of 18,624 patients hospitalised for acute coronary syndromes, an invasive strategy was planned at the beginning of the study for 13,408 (72 percent). Randomly, patients were assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300 – 600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for six to twelve months. All patients were given aspirin. The primary endpoint was any of cardiovascular death, myocardial infarction, or stroke.
Results indicated that patients in the ticagrelor group were 16 percent less likely to experience the primary endpoint than those in the clopidogrel group. The endpoint of cardiovascular death, heart attack, or stroke occurred in fewer patients in the ticagrelor group than in the clopidogrel group (event rate at 360 days 9.0 percent compared to 10.7 percent). Furthermore, the risk of death was considerably reduced from 5.0 percent (clopidogrel) to 3.9 percent (ticagrelor). There was a reduction in the risk of dying over one year of around one fifth. Blood clots developing inside heart stents were also significantly reduced. On the other hand, there was no statistically significant disparity between clopidogrel and ticagrelor groups in the rates of total major bleeding (12 percent each group), or severe bleeding (3 percent both groups).
The authors comment: “Patients given ticagrelor had significant and clinically relevant reductions in cardiovascular and total deaths, myocardial infarction, and stent thrombosis, without an increase in risk of major bleeding. The benefits with respect to clinical events and stent thrombosis were consistent whether or not patients were given standard or higher loading doses of clopidogrel, as advocated for patients undergoing invasive strategies.Thereby, ticagrelor has important advantages, and improves the early invasive and long-term management of patients with acute coronary syndromes.”
They say in conclusion: “We estimate that use of ticagrelor instead of clopidogrel for 1 year in 1,000 patients with acute coronary syndromes and who are planned to undergo an invasive strategy at the start of drug treatment would lead to 11 fewer deaths, 13 fewer myocardial infarctions, and six fewer cases of stent thrombosis without an increase in the rates of major bleeding or transfusion.”
In an associated comment, Dr Gregg W Stone, Columbia University Medical Center, Cardiovascular Research Foundation, New York, USA, remarks: “These compelling results support ticagrelor as a new standard of care in acute coronary syndromes. However, a personalised approach to drug selection should be used wherein each patient’s individualised risk of ischaemia versus bleeding is considered. Clopidogrel might still be appropriate for selected patients who are at relatively low risk of myocardial infarction or stent thrombosis and/or high risk of major bleeding, and/or for whom non-compliance with ticagrelor because of cost or other considerations (eg, twice daily dosing) is a concern. Nonetheless, the introduction of ticagrelor, a more potent and effective agent which is as safe as its predecessor, is a landmark event that should redefine the care of patients with acute coronary syndromes.”
“Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study”
Christopher P Cannon, Robert A Harrington, Stefan James, Diego Ardissino, Richard C Becker, Håkan Emanuelsson, Steen Husted, Hugo Katus, Matyas Keltai, Nardev S Khurmi, Frederic Kontny, Basil S Lewis, Philippe Gabriel Steg, Robert F Storey, Daniel Wojdyla, Lars Wallentin for the PLATelet inhibition and patient Outcomes (PLATO) investigators
DOI: 10.1016/S0140-6736(09)62191-7
The Lancet
Written by Stephanie Brunner (B.A.)