Large Study of Peripheral Artery Disease Clarifies Treatment Options
The finding that the drug ticagrelor proved no better than clopidogrel in reducing cardiovascular events for patients with peripheral artery disease should both assure patients about current treatments and demonstrate that new options are still needed, Duke Clinical Research Institute investigators say.
The findings, reported Nov. 13 at the annual American Heart Association Scientific Sessions meeting and in the New England Journal of Medicine, followed a four-year study of nearly 14,000 patients throughout the world. It was the largest study of patients with peripheral artery disease, which is a narrowing of the vessels to the extremities.
“This is a disease that affects a lot of people -- more than 8 million in the United States and millions more worldwide,” said corresponding author Manesh R. Patel, M.D., chief of Duke’s Division of Cardiology and member of the Duke Clinical Research Institute (DCRI). “But there aren’t many therapies to treat the condition, so it’s important to determine if new therapies offer any advantages, but also if current therapies are sufficiently effective.”
Patel said the study provided a head-to-head comparison of a potential new therapy, ticagrelor, which is marketed as Brilinta, against the current standard of care, clopidogrel, which is now generic but is also marketed under the brand name Plavix.
Both are anti-platelet drugs. Aside from clopidogrel, the only other anti-clotting agent that has been tested as a single therapy for peripheral artery disease is aspirin, which showed only a modest reduction in cardiovascular events compared with a placebo pill.
Ticagrelor is currently approved for use in patients with acute coronary syndrome and post-myocardial infarction; in studies of patients with those conditions, the drug in combination with aspirin showed evidence of benefitting peripheral artery disease.
In the comparative study led by DCRI and CPC Clinical Research at the University of Colorado, the researchers found that 10.8 percent of the patients taking ticagrelor had a heart attack, ischemic stroke or cardiovascular death, compared to 10.6 percent of clopidogrel-treated patients. Major bleeding occurred at the same rate -- 1.6 percent -- of patients treated with either ticagrelor or clopidogrel.
“Given the initial evidence, ticagrelor was considered a potent anti-platelet agent with potential benefit also in patients with peripheral artery disease,” Patel said. “Our trial demonstrates the hazards of extrapolating evidence from coronary artery disease populations to patients with peripheral artery disease.”
Patel said the findings demonstrate that ticagrelor could be considered a reasonable alternative for patients who could not take clopidogrel, but that new treatments are needed to give patients more options.
“There is still a huge unmet need and high event rates for people with this disease,” Patel said. “We need other therapies to address this disease burden. Future trials should evaluate well-defined peripheral artery disease populations, and take into account the procedures, drugs and devices used to treat symptomatic peripheral artery disease.”
In addition to Patel, study authors include principal investigator William R. Hiatt from the University of Colorado School of Medicine and CPC Clinical Research, and co-principal investigator F. Gerry R. Fowkes of Usher Institute of Population Health Sciences and Informatics. They were joined by Gretchen Heizer, Jeffrey S. Berger, Iris Baumgartner, Peter Held, Brian G. Katona, Kenneth W. Mahaffey, Lars Norgren, W. Schuyler Jones, Juuso Blomster, Marcus Millegård, and Craig Reist on behalf of the International Steering Committee and Investigators of the EUCLID Trial (Examining Use of tiCagreLor In paD).
The study received funding from AstraZeneca, which markets ticagrelor.