Merck Blood Thinner Stops Heart Attacks With Risk of Bleeding

A study of an experimental blood thinner from Merck & Co. (MRK) showed that while the drug helped thwart heart attacks it raised the risk of brain bleeding, a side effect that could stymie its approval.

The three-year study of 26,449 patients who had heart attack, stroke or leg artery disease, found those who got Merck’s vorapaxar along with standard therapy were 13 percent less likely to have another heart attack or die from cardiovascular causes than those on standard treatment. More patients on the drug also had serious bleeding, according to data reported today at the American College of Cardiology meeting in Chicago.

The findings are unlikely to be good enough to get U.S. marketing approval, said Steven Nissen, a cardiologist at the Cleveland Clinic who wasn’t involved in the study. New studies are needed to prove vorapaxar can be used in some patients without excess bleeding, he said.

“The results are disappointing,” said Nissen. “The bottom line is it is extremely difficult to make the case that the benefits exceed the risks here.”

In January 2011, Merck narrowed the scope of the trial to stop testing the drug in stroke patients and halted another vorapaxar trial entirely after doctors monitoring the results found an increased risk of brain hemorrhage in those patients. Merck, based in Whitehouse Station, New Jersey, later took a $1.7 billion charge to write down the value of the drug.

Efficacy Goal

Merck Vice President Francis Plat, in an interview at the meeting, called the company-funded vorapaxar study “positive” because it achieved its efficacy goal of preventing heart attacks and heart-related deaths. He said the company is discussing with top cardiologists what role the new medicine might play and which patient groups are likely to benefit.
Until those talks are done, “it is difficult for us to anticipate any strategy in terms of filing” for regulatory approval, he said.

Two clinical trials involving the investigational thrombin receptor antagonist vorapaxar (Merck, Whitehouse Station, NJ) have been tweaked, with investigators for one trial immediately stopping use of the drug in stroke patients .

In an update issued Wednesday by study chair Dr Eugene Braunwald (Brigham and Women's Hospital, Boston, MA) to investigators, Braunwald stated that the data and safety monitoring board (DSMB) had communicated that, based on all of the data (safety and efficacy) available from both trials, it was recommending that subjects with a history of stroke not receive vorapaxar. "[The DSMB has] observed an increase in intracranial hemorrhage in patients with a history of stroke that is not outweighed by their considerations of potential benefit."

David Morrow, a cardiologist at Brigham & Women’s Hospital in Boston who led the study, said that the drug’s benefit was compelling in the subset of 17,779 patients who had previous heart attacks. In that group, vorapaxar reduced the risk of heart attacks, strokes and cardiovascular death by 20 percent.