|Possible for new antiplatelet drug to enter market based on trial results. Source: South Dakota State University|
Eli Lilly and Daiichi Sankyo’s antiplatelet drug, prasugrel, reduces heart risks, but has a higher bleeding rate compared to the gold standard drug, Plavix or clopidogrel, for patients who have undergone percutaneous coronary intervention (PCI), according to a late-breaking clinical trial presented at the American Heart Association’s Scientific Sessions held this week in Orlando, Fla.
Elliot Antman, MD, director of Samuel A. Levine cardiac unit at Brigham and Women’s Hospital in Boston, and professor of medicine at Harvard School of Medicine in Boston, made the presentation on behalf of Eli Lilly and Daiichi Sankyo.
The TRITON-TIMI 38, an international, double-blind phase III trial, compared single dosage regimens of prasugrel and clopidogrel, which are both in a class of medications called thienopyridines.
In regard to Plavix, Antman said that “although [prasugrel] is an effective drug, patients continue to have [cardiac] events. Therefore, there is a clinical need to improve on the benefits observed with clopidogrel.”
The trial consisted of 13,608 patients with moderate to high risk for acute coronary syndrome (ACS), who were scheduled to undergo PCI. Participants were randomized at 707 sites in 30 countries, and were given either prasugrel (60mg as a one-time “loading” dose, followed by a daily 10 mg maintenance dose) or clopidogrel (300mg loading dose and a daily 75mg maintenance dose) for up to 15 months after PCI.
The primary efficacy endpoint (death from cardiovascular causes, heart attack or stoke) was significantly lower on prasugrel (12.1 percent of patients randomized to clopidogrel and 9.9 percent of patients randomized to prasugrel). The prasugrel dose was also associated with a significantly lower incidence of stent thrombosis, urgent target vessel revascularization and heart attacks.
However, major bleeding was significantly higher with prasugrel (2.4 percent of patients versus 1.8 percent of patients randomized to clopidogrel). But, the balance of efficacy and safety, net clinical benefit (all cause mortality, nonfatal MI, nonfatal stroke, or nonfatal major bleed) favored prasugrel.
Antman said that many of the patients who did not do as well with the prasugrel dosage were elderly and had a low body weight.
According to Antman following his presentation at a press conference, “96 percent in trial should take this drug, or a slightly modified dose.” He also disagreed that the benefits of prasugrel leveled out with Plavix after the first 60 days following PCI.
Antman believed it was premature for anyone to comment about the FDA approval, but he said that “prasugrel is definitely an approvable drug on these results.” Antman also stressed that additional trials would be costly and time-consuming.
Gordon Tomaselli, MD, chairman of the AHA committee on the scientific sessions program, as well as chief of the cardiology division at Johns Hopkins University School of Medicine, concurred that trials are complicated: “You have to realize how much time, money and effort these studies take.” However, in order for prasugrel to receive FDA approval, he added, “it’s my guess that’s what will need to occur.”