There is nothing like a pipeline setback to have Wall Street second guessing your every move. But that is the predicament that Merck execs face today after disclosing an experimental clotbuster is no longer being given to patients in one study called TRACER and to some patients in another Phase III trial called TRA-2P after the drug was considered inappropriate for patients who suffered a stroke.

Neither Merck nor the researchers offered much explanation for the move (see the statements here and here), although they tried to place a spin on the sour disclosure by noting the trial endpoints had, nonetheless, been reached.

But the news is hurting Merck stock, because the drug was widely seen as one of the most important products that came with the Schering-Plough acquistion. Until now, the clotbuster was pegged as a potential blockbuster with sales reaching more than $1.1 billion in revenue by 2015, representing as much as 2.5 percent of total revenues, according to Sanford Bernstein analyst Tim Anderson.

For the moment, the assumption is that vorapaxar caused unacceptable bleeding, a typical worry involving anti-platelet therapies. And so the setback “will partly call into question” the justification for buying Schering-Plough, Anderson writes in an investor note. Of course, there is also the Remicade rheumatoid arthritis treatment, but the rights are being challenged by Johnson & Johnson and the dispute is being arbitrated with a possibility that Merck may lose some future revenue.

“As Merck is a large company, especially after the acquisition of Schering-Plough, losing vorapaxar – while clearly a negative – will not affect Merck’s financials substantially, but it does strip away the company’s highest profile pipeline drug,” writes Anderson whose note carries this headline: ‘Vorapaxar Bites the Dust.’

Over at Deutsche Bank, Barbara Ryan speculates two things; first, significantly increased bleeding is not a concern with maintenance dosing for secondary prevention for myocardial infarction or peripheral artery disease and, second, the incidence or severity of stroke may have been higher with vorapaxar therapy and the drug should be contraindicated in patients with prior stroke, who are at much higher stroke risk, she wrote in an investor note. “There are lots of other possibilities,” she concludes, “but the bottom line is that this is a significant setback for the program.”