For years doctors have known that thinning the blood, using drugs such as aspirin, can reduce heart attacks. So for years they have used a super aspirin, Plavix, to prevent heart attacks in patients who have angioplasty, and are at greater risk for developing clots.
Today at the country's biggest heart meeting, heart specialists heard about a new drug called Prasugrel, even more powerful at blood thinning than Plavix. A new study of more than 13,000 patients found that Prasugrel significantly reduced cardiovascular complications, including clots in stents.
The lead investigators of the so-called TRITONTIMI 38 study said their data suggested that 96 percent of patients who were high risk for heart events and were having a stent could be potential candidates for this drug, which is not yet approved.
Many heart specialists at the American Heart Association Scientific Sessions in Orlando, Fla., Sunday were enthusiastic about the success of the drug, which reduced the number of heart events in the study participants from 19 percent to as much as 50 percent.
"This is the first validation that more-powerful oral anti-platelet drugs further reduce coronary complications," said Deepak Bhatt, associate director of the cardiovascular coordinating center at Cleveland Clinic, who wrote the editorial accompanying the study in the New England Journal of Medicine.
However, in the world of anti-platelet therapies, more isn't always better.
Heart specialists spent the day debating whether the price for this success at blood thinning was too high. The more powerful ability to thin the blood means that the drug also causes various kind of bleeding, some of which can be fatal. Major bleeding happened in 2.4 percent of patients receiving Prasugrel and 1.8 percent receiving Plavix.
"I think the bleeding was too excessive to warrant immediate use of this new agent," said Adolph Hutter, associate director of the coronary care unit at Massachusetts General Hospital.
Dr. Elliot Antman, of Brigham and Women's Hospital, one of the lead investigators of the study, said the risk to benefit ratio suggests that 4 percent of patients — those who had a previous stroke or so-called mini-stroke — should not take the drug. Antman said 16 percent, including those older than 75 and less than 132 pounds, might benefit if the dose were adjusted.
"One great thing about the Triton Trial is it points out that the risk and benefit balance is not something you can talk about for the whole population," said Robert Califf, vice chancellor for clinical research and professor of medicine in the Division of Cardiology at Duke University. "Some people get more benefit than risk and other people have more risks than benefit relative to the alternative, [Plavix]."
According to Cindy Grines, vice chief of academic affairs and an interventional cardiologist at William Beaumont Hospital, this trade-off between the benefits and risks of blood-thinner drugs is not a new concept to physicians, and shouldn't scare doctors from prescribing the medication or patients from using it. "There are no free lunches — every drug that thins the blood to reduce clotting will cause bleeding," Grines said.
After the study was presented, Dr. Eric Topol, director of the Scripps Translational Science Institute, told the heart meeting that there were two heart attacks prevented for every major bleed caused by Prasugrel.
Topol called the Prasugrel results "incremental efficacy" and said the trial only suggests the drug should be used in a "narrow group of patients." Topol was the heart specialist invited to comment on the study.
"Overall, the number of cardiac events averted was larger than bleeding events caused by Prasugrel," said Harlan Krumholz, professor of medicine, epidemiology and public health at Yale University. "But the clinical decision can be improved by tailoring it to the patient's risk profile for cardiac events and bleeding."
Bhatt specifies in his editorial the subgroups of patients who received no clinical benefit from Prasugrel — specifically, patients older than 75, those who are underweight, those with cerebrovascular disease and those with a history of stroke. Moreover, because Prasugrel increases risk of heavy or even fatal bleeding, patients who are expected to receive major heart surgery, such as coronary artery bypass graft surgery, should not consider this potent drug thinner as a treatment option.
Because the trial was successful in determining subgroups of patients who would receive no clinical benefit from Prasugrel, many doctors and surgeons believe that if prescribed responsibly — that is, taking into account each patient's specific risk factors — Prasugrel has the potential to become a positive addition to the current standard of treatment for heart attack patients.
"If the protocol of the study is followed and the patient does not receive [Prasugrel] until the angiography is done, and … complex or higher risk anatomy is avoided, then the risk of needing emergency surgery and severe hemorrhage is very low and acceptable," said Nicholas Smedira, surgical director of the Kaufman Center for Heart Failure.
More importantly, many physicians stress the need for public education on the topic of which patients will and which will not benefit from the use of Prasugrel.
"If CABG [coronary artery bypass graft] is needed and you are on this drug, it will be a problem," said Thoralf Sundt, professor of cardiovascular surgery at the Mayo Clinic in Rochester, Minn. "It is important for the public to understand this as these drugs get pushed onto the masses with direct marketing."