New heart drugs hailed as breakthrough treatments by researchers are struggling to gain traction among prescribing doctors, posing a headache for makers such as Novartis, which reported more weak sales for its Entresto medicine on Thursday.

Novartis has touted the novel heart failure drug as a $5 billion-a-year seller and is banking on the product to help offset loss of patent protection on its blockbuster cancer medicine Glivec.

Yet first-quarter sales of $17 million were well below analyst expectations of $25-30 million and the company now predicts 2016 sales of just $200 million, or less than half of consensus forecasts compiled by Thomson Reuters Cortellis.

Novartis' problems are not unique. Sanofi and Amgen are also battling to win prescriptions for their new so-called PCSK9 cholesterol-fighting injections Praluent and Repatha.

Such difficulties are in marked contrast to other disease areas such as cancer, where Bristol-Myers Squibb's new treatment Opdivo is an outstanding commercial hit. Novartis' own psoriasis drug Cosentyx is also beating expectations.

U.S. heart specialist Richard Chazal, president of the American College of Cardiology (ACC), believes slow uptake of pricey new heart drugs highlights the peculiar difficulties surrounding such medicines, which are typically given for life.

"Cost is a problem," he said in an interview. "There is concern on the part of many clinicians that if patients are reasonably stable and one starts a new medicine then they may become discouraged by the cost and actually stop taking medication."

The U.S. list price for Entresto is around $4,500 a year, while the PCSK9 drugs cost about $14,000.

Adding to doctors' reticence is the lack of specific guidelines from professional bodies such as the ACC, American Heart Association and European Society of Cardiology.

While updated guidelines covering the potential use of Entresto are in the works, the delay has frustrated some experts such as Milton Packer, one of the cardiologists who led trial research into Entresto that found it cut the risk of both cardiovascular death and admissions to hospital by a fifth.

Packer complained in a journal article last month about the fact that the guideline process had so far been "silent".

For Praluent and Repatha there is the added complication that while both drugs have been shown to reduce cholesterol dramatically, clinical trials are still ongoing to prove this will actually cut heart attacks as expected.

In the long term, most experts still predict the new clutch of heart drugs will become multibillion-dollar-a-year sellers, but it is going to be a longer haul than initially anticipated.

"We're extraordinarily fortunate to have these wonderful new tools that science shows us can potentially improve outcomes," said Chazal. "How to use them is something we are still working through but I think we will see increased uptake in the next 12 months."

In a bid to invigorate Entresto sales, Novartis said it was expanding its U.S. field force of sales representatives, starting this month, and also launching a direct-to-consumer advertising campaign.

However, the combination of lower sales and increased marketing spend suggests that Entresto - arguably the Swiss company's single biggest new drug hope - will take time to contribute significantly to the bottom line.

(Editing by Mark Potter)