New drugs to prevent dangerous blood clots promise to shake up the market but pharmaceutical companies face an uphill fight on price.

Cost will be key for both AstraZeneca's Brilinta and Boehringer Ingelheim's Pradaxa as they jostle for sales against cheap generics and a pipeline of rival treatments, at a time of unprecedented pressure on healthcare budgets.

Heart experts from Europe and the US, meeting this week at the European Society of Cardiology congress, were impressed by clinical results for both drugs but conscious of pricing.

"The economic situation is not easy," said Kurt Huber of Wilhelmine Hospital in Vienna. "I would like to be free to use a more active and potent drug in patients where there is a clear advantage ... but there could be restrictions, especially if the price difference becomes huge."

Brilinta is gunning for Sanofi-Aventis and Bristol-Myers Squibb's $9 billion-a-year drug Plavix as a treatment for heart-attack patients.

Pradaxa is a potential replacement for warfarin, an old and problematic drug, in patients at risk of stroke due to a quivering heart. Experts believe it may be the first of a new generation of oral anticoagulants with sales potential of more than $10 billion.

But neither is the only game in town.

Plavix already has one competitor from Eli Lilly and Daiichi Sankyo in Effient, though it is hampered by increased bleeding risk. And other rival anti-platelets are in development, including Novartis and Portola Pharmaceuticals' elinogrel, which is due to enter final-stage trials in 2010.

What price a heart attack?

More importantly, Plavix is set to face generic competition in the US from 2012, drastically changing the market dynamics. In parts of Europe, it is already off patent.

"The biggest hurdle to widespread adoption of either Effient or Brilinta has yet to come," said Tim Anderson, an industry analyst at Sanford Bernstein.

"The price disparity between Effient, Brilinta and generic Plavix could tip those payers, patients, physicians who are on the fence about which drug to use to choose the least costly alternative -- i.e. generic Plavix."

For some European doctors, the issue is already very real, including Steen Dalby Kristensen of Aarhus University Hospital in Denmark, where generic Plavix has recently gone on sale.

"The first generic was not that much cheaper but I'm sure the price will really drop ... there will be health-economic issues surrounding that. How much extra will we pay to save an ischaemic event (heart attack or stroke)?"

Arguably, unlisted German drugmaker Boehringer has an easier task than AstraZeneca, since it enjoys a lead of at least a year over its rivals in replacing warfarin, provided Pradaxa is approved by the end of 2010 as hoped.

But Bayer and Johnson & Johnson are chasing hard with Xarelto, which may be even more effective -- as long as it does not raise bleeding rates excessively.

Other oral anticoagulants in development include Pfizer and Bristol's apixaban and Merck and Portola's betrixaban. And AstraZeneca has a follow-up drug in mid-stage tests it hopes will do better than Exanta, which famously failed to replace warfarin five years ago because of liver toxicity.

Bill Lis, head of business and commercial development at Portola, predicts the oral anticoagulant market could be worth $14 billion in annual sales by 2017 or 2018.

Boehringer hopes for pricing headroom, given its new drug's superior profile to warfarin and the fact it does away with the need for regular blood monitoring costing $50 to $500 a month.

Payers, however, are likely to take a long, hard look at Pradaxa before the signing the cheques.

"It's going to be a battle," said Alfred Bove of Temple University in Philadelphia and president of the American College of Cardiology. "I can tell you we are going to be on the phone frequ