MASAB Medical Memo #3, November 2, 2017
The PIONEER Trial, Three May End Up Being a Crowd
by Samuel A. Berkman, MD, FACP, Clinical Professor of Medicine, Division of Hematology-Oncology, UCLA
People with heart disease often require the placement of a stent as part of their treatment. Many need medication — most often aspirin and clopidogrel — to keep the stent from becoming blocked. These are called antiplatelet drugs. Some of these patients also have Afib and must take blood thinners, typically warfarin, to prevent the formation of blood clots that could otherwise cause a serious stroke. This combination of drugs successfully addresses the two problems, but has an important side effect, and that is major bleeding risk. This medication “cocktail” is essential, but physicians and patients have been looking for alternatives that would have less bleeding risk.
The Pioneer trial was an ambitious, important comparison of three treatment regimens to help identify an effective, and less risky, alternative therapy. The study was conducted at 426 sites in 26 countries and involved 2,124 patients, so people can have confidence in the results.
The study had three arms and patients were randomly assigned to one of the three. The first alternate treatment group received only two drugs, clopidogrel and rivaroxaban, a newer blood thinner. The second alternate treatment group consisted of very low-dose rivaroxaban, clopidogrel and aspirin. Group three was the control group and they received the traditional “triple therapy” of aspirin, clopidogrel, and warfarin.
The trial measured the number of patients in each arm who experienced clinically significant bleeding.
What did the study show? The patients in Groups 1 and 2 (alternate therapies) had decreased bleeding versus the control or traditional triple therapy (16.1% in Group 1, 18% in Group 2, and 26% in Group 3).
Another important finding was that Group 1 had no increase in strokes, heart attacks, and stent blockages compared to Group 3. Furthermore, both rivaroxaban groups had a statistically significant decrease in hospitalizations, which would potentially save patients and families stressful and expensive hospitalizations and procedures. Data from the study also showed that stent blockage was only seen in 0.8% of the patients in Group 1, the group which did not receive any aspirin. This was in contrast to 0.9% in Group 2 and 0.7% in Group 3, both of which received three drugs including aspirin. In the past, aspirin has been considered crucial in stent patients, particularly during the first month post stent placement as stent blockage is viewed by cardiologists as a catastrophe.
Therefore, what this study suggests is that many patients who have both Afib and a stent may no longer need the standard triple therapy with the high bleeding risks. The newer blood thinner reduced that risk. These individuals will continue to need multiple therapies, one to protect the stent from clogging and one to prevent blood clots. However, triple therapy may be replaced by “double therapy,” as aspirin appears to be no longer needed in the cocktail and may be on the way out. Further studies and regulatory approval will be needed before this is routinely recommended.
1.Gibson, CM, Mehran RM, Bode C et al, Prevention of bleeding in patients with atrial fibrillation undergoing PCI. New England Journal of Medicine 2016; 375 (25) 2423-2434
2. Gibson CM, Pinto DS, Chi G. Recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with two treatment strategies of Rivaroxaban or a dose of adjusted oral vitamin K antagonist treatment strategy. Circulation. 2017; 135 (4): 323-333.
3. Berkman S.A., Prevention of Bleeding in Patients with atrial fibrillation undergoing PCI (Pioneer; Three may end up being a crowd, Clinical and Applied Thrombosis/Hemostasis published online open access 5/2017