The hunt for new heart drugs is losing momentum as resources are switched to other areas, notably cancer research, where investors get a better bang for their buck.
Cardiologists fear the fight against heart disease could stall as a result, following major advances in recent decades marked by the advent of drugs to lower cholesterol and blood pressure and to prevent dangerous blood clots.
The disparity between advances in cancer and heart medicines is already stark. Since the beginning of 2012, 17 cancer drugs been approved by the Food and Drug Administration, compared with just three for heart disease.
"There is a clear move of R&D from cardiovascular to cancer and other areas," said Michel Komajda, a heart specialist at Pitie-Salpetriere Hospital in Paris and a former president of the European Society of Cardiology (ESC).
Like many of his colleagues gathered at the annual ESC congress this week in Amsterdam, Komajda is worried.
Despite the giant drugmakers' stand touting heart medicines at this week's meeting of some 30,000 doctors, investment in cardiovascular medicine is ebbing—prompting calls for an urgent rebalancing of research priorities.
"There is a view among some that because we have already made a lot of progress in cardiovascular medicine then maybe it doesn't make sense to invest any more," Komajda said. "But there are still some big areas where we need progress, including acute heart failure, which is a growing problem because of an aging population."
To some extent, cardiology is a victim of its own success. By any measure, the global war on heart disease to date has been successful, because of better drugs as well as prevention strategies such as anti-smoking campaigns.
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In Europe, the death rate from cardiovascular disease has been cut in half over the past 30 years, while the risk of dying within 30 days of a heart attack has been halved in just 20 years.
No. 1 killer
Yet cardiovascular disease remains the No. 1 killer worldwide, and doctors fear a renewed epidemic of problems in 20 to 30 years time as a new generation of overweight and obese youngsters reaches middle age.
"It's a huge concern," said Patrick O'Gara of Boston's Brigham and Women's Hospital, who is also president-elect of the American College of Cardiology. "We need to replenish the fuel that drives the engine."
Many patients remain at risk of clogged arteries, despite taking cholesterol-lowering statins, while heart failure—where the heart fails to pump blood adequately—remains a deadly disease that has seen little progress in treatment in 40 years.
Developing new heart drugs takes particularly heavy spending, with uncertain returns. Further, patent expirations mean many previously profitable heart drugs are now available as cheap generics, reducing drugmakers' revenue.
In contrast to oncology, where a better understanding of the genetics behind different tumors means drugs can be tested rapidly in small groups of highly targeted patients, heart drugs still need large and lengthy studies to prove a benefit.
Each of these tests can cost hundreds of millions of dollars, raising doubts about whether funding cardiovascular research is worth it—especially after recent high-profile setbacks.
Both Pfizer and Roche had disappointing results with drugs designed to raise levels of "good," or high-density lipoprotein, cholesterol.
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The relatively bare heart medicine cabinet was evident at the ESC meeting, where negative clinical trials outnumbered positive ones and the biggest good news a was a fourth-to-market new oral anticoagulant from Daiichi Sankyo.
Learning from cancer
Some heart doctors argue it is time to learn from cancer.
"We need to take a lesson from our colleagues in oncology where the approaches are really very smart," said Keith Fox, professor of cardiology at Edinburgh University. "We need to move from blanket approaches to more targeted approaches."
So far, however, working out how to target heart drugs effectively has proved elusive—a fact that has not been lost on investors in emerging medical technologies, according to Briggs Morrison, head of global medicines development at AstraZeneca, which is investing in both areas.
"If you are a biotech company and you go into oncology, there is a very rapid path to approval with a small patient population that means investors can get a return," he said.
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"In cardiovascular disease, it's a long road, it's a lot of patients, and it's a big investment."
What the cardiovascular field needs is a "Glivec moment," according to American Heart Association President Mariell Jessup, referring to the Novartis leukemia drug that kick-started interest in targeted cancer drugs a decade ago.
One area that might deliver fresh impetus is the emerging class of experimental cholesterol-lowering drugs known as PCSK9 inhibitors. They are now in mid-stage studies.
Delivered by injection, the man-made antibodies offer a new way of fighting atherosclerosis, or the build-up of artery-clogging fatty deposits—but still need to prove themselves in late-stage tests.
"There are other discoveries out there like this that we need to be making," he said. "We need to peel away at this onion of atherosclerosis because we understand only about a third of the risk factors responsible for it."