Feature | March 17, 2010

Ticagrelor Shows Lower Mortality Than Clopidogrel After CABG

March 17, 2010 – New Results from PLATO trial suggest ticagrelor (Brilinta) leads to lower mortality and no increased risk of bleeding when compared to clopidogrel (Plavix) in patients with acute coronary syndrome who undergo coronary artery bypass graft (CABG) surgery.

Patients are less likely to develop fatal outcomes when given ticagrelor instead of clopidogrel as an anti-platelet medication, according to research presented this week at the American College of Cardiology’s 59th annual scientific session. ACC.10 is the premier cardiovascular medical meeting, bringing together cardiologists and cardiovascular specialists to further advances in cardiovascular medicine.

Ticagrelor is pending FDA review and is not yet available in the U.S. market. It is anticipated to be a big competitor to clopidogrel when it is cleared, possibly in the next year. Unlike clopidogrel, the anti-platelet agent’s effects are reversible.

Examining a subpopulation of 1,261 patients in the Platelet Inhibition and Patient Outcomes (PLATO) Trial who underwent CABG, researchers found 10.5 percent of patients given ticagrelor and aspirin within seven days of their procedure had a primary composite endpoint that included cardiovascular death, heart attack, and stroke, compared with 12.6 percent of patients given clopidogrel and aspirin. This reduction was consistent with the overall effect of ticagrelor versus clopidogrel in the main PLATO study.

Patients on ticagrelor had a total mortality rate of 4.6 percent, compared to 9.2 percent for patients on clopidogrel, and the cardiovascular death rates were 4 and 7.5 percent, respectively. When examined individually, there was no statistically significant difference between the two groups for heart attack and stroke, and there was no significant difference in CABG-related major bleedings.

“Ticagrelor seems to be a very promising alternative to clopidogrel for patients with acute coronary syndrome who might be candidates for CABG surgery, because of the significant reduction in mortality and the similar bleeding rate,” said Claes Held, M.D., Ph.D., associate professor of cardiology at the Uppsala Clinical Research Center and Department of Cardiology, and the substudy’s lead researcher. “Because there is such an obvious risk of severe bleeding and fatal complications during surgery, patients with a potential need for CABG comprise an especially important group, for which platelet inhibitors with a better safety-efficacy profile are needed.”

The results of the analysis are in line with data recorded from the overall PLATO trial – a double-blind study which randomized 18,624 patients in 43 countries with acute coronary syndrome to receive treatment with either ticagrelor or clopidogrel. The overall study found an efficacy advantage for ticagrelor compared with clopidogrel and no significant difference in major bleeding. At the time of the original PLATO trial’s publication, ticagrelor was the first antiplatelet agent to demonstrate a reduction in cardiovascular and total deaths in patients with acute coronary syndrome versus clopidogrel.

Both drugs are oral anti-platelet medications and are designed to prevent the formation of blood clots by inhibiting the clumping of platelets, but they belong to two different chemical classes. Clopidogrel is a thienopyridine, which requires metabolic conversion in the body after ingestion, leading to a delayed onset of action. Thienopyridines are also associated with wide inter-individual variability in platelet inhibition (leading to some clopidogrel “nonresponders”) and irreversible binding to P2Y12 receptors, which eliminates the ability to recover platelet function until the body produces new platelets.
By contrast, ticagrelor, which is in a new chemical class called the cyclopentyl-triazolo-pyrimidines, does not require metabolic conversion; binds directly to P2Y12 receptors which leads to more complete platelet inhibition; and binds resversibly, allowing for faster recovery of platelet function.

“With ticagrelor, you get a more efficient and predictable platelet inhibition response but still a more rapid and reversible offset than with clopidogrel,” said Dr. Held.

Although Dr. Held notes that the substudy results are provocative, he adds that caution is warranted in interpreting the findings, especially because of the study’s retrospective, post-randomization comparison between the treatment arms.

The PLATO trial was funded by AstraZeneca, maker of ticagrelor. Clopidogrel is manufactured by Bristol-Myers Squibb and Sanofi-Aventis.

The statistical analyses of this substudy were independently performed by Uppsala Clinical Research Center, Duke Clinical Research Institute, and AstraZeneca.

For more information: www.astrazeneca-us.com.

Related Content

Abbott, Absorb bioresorbable stent, dissolving, UAB, University of Alabama at Birmingham, first in state
News | Stents Bioresorbable| July 26, 2016
On July 20, Massoud Leesar, M.D., of University of Alabama at Birmingham Hospital implanted a patient with Absorb, the...
CMS, Overall Hospital Quality Star Rating, national distribution, quailty of care
News | Business| July 26, 2016
July 25, 2016 — The Centers for Medicare and Medicaid Services (CMS) announced that it expects to launch its new Over
CMS, bundled payment models, coronary artery bypass surgery, ACC, STS
News | Business| July 26, 2016
July 26, 2016 — The Centers for Medicare & Medicaid Services (CMS) has proposed the creation of new...
Stryker Sustainability Solutions, Angiodynamics Soft Vu Omni Flush Angiographic Catheters, recall
News | Angiographic Catheter| July 25, 2016
Stryker Sustainability Solutions (formerly Ascent Healthcare Solutions) is recalling Angiodynamics Soft Vu Omni Flush...
Million Hearts Cardiovascular Disease Risk Reduction Model, CMS, reduce heart attacks and strokes, participants
News | Patient Engagement| July 22, 2016
July 22, 2016 — The Centers for Medicare & Medicaid Services (CMS) recently announced 516 awardees in 47 states,
heart failure, after first heart attack, cancer risk, JACC study
News | Cardiac Diagnostics| July 21, 2016
People who develop heart failure after their first heart attack have a greater risk of developing cancer when compared...
Absorb, bioresorbable stent, BVS

The Abbott Absorb stent gained FDA clearance in July 2016. It has metallic markers at each end so it can be visualized for proper positioning under angiographic X-ray imaging. 

Feature | Stents Bioresorbable| July 21, 2016 | Alphonse Ambrosia, D.O.
Some have labeled bioresorbable scaffolds (BRS), also known as bioresorbable stents, as the fourth evolution of inter
Sponsored Content | Videos | Inventory Management| July 19, 2016
You have bigger priorities than managing inventory.
Abbott Absorb bioresorbable stent, dissolving BVS, first West Coast implant, Good Samaritan Hospital Los Angeles
News | Stents Bioresorbable| July 19, 2016
Good Samaritan Hospital, Los Angeles, is the first hospital on the West Coast to offer patients with coronary artery...
Medtronic, In.Pact Admiral drug coated balloon, DCB, FDA approval, 150 mm length
Technology | Drug-Eluting Balloons| July 18, 2016
Medtronic plc has received U.S. Food and Drug Administration (FDA) approval for the IN.PACT Admiral drug-coated balloon...
Overlay Init