Raising good cholesterol, a goal pursued by Eli Lilly and Co. and Merck & Co. as the next milestone in cardiac care, may not cut heart-attack risk, says a study that challenges the development of drugs that may someday generate billions of dollars in sales.

The report, in the United Kingdom medical journal The Lancet, found that people with a genetic condition that causes high HDL have the same heart-attack risk as the general population. The results come from a computer analysis of 20 studies.

The authors suggested the link found earlier between good cholesterol and lower heart risk may come from more subtle lifestyle factors tied to higher HDL levels. If so, it brings into question the development of medicines such as Merck’s anacetrapib, an HDL booster that Tony Butler, a Barclay’s Capital analyst in New York, said on May 7 may generate $4 billion in peak revenue once approved.

“This will have a sobering effect; it would have to,” said John LaMattina, a senior partner at PureTech Ventures and former head of research and development at Pfizer Inc. “HDL has always been a controversial area. You have a question that you have to be willing to commit over a billion dollars in order to get the answer, and that is a very daunting commitment.”

Scientists have said HDL works by sweeping the bad form of the fatty substance known as LDL, or bad cholesterol, out of arteries, reducing clogs. The Lancet study analyzed 20,913 heart attack cases and 95,047 control subjects, the report said.

Steven Nissen, the chief of cardiology at the Cleveland Clinic in Ohio, said The Lancet report runs counter to earlier studies that have found people with naturally high levels of HDL do have lower rates of heart disease.

“This study isn’t definitive,” Nissen said. “It doesn’t support the hypothesis, but it doesn’t rule it out either. I remain cautiously optimistic.”

Merck is in the process of a 30,000-person trial studying anacetrapib that’s slated to be completed in 2017, as part of the final phase of testing normally required for U.S. marketing approval. The company is racing Indianapolis-based Lilly to market the new family of medicines.

Pamela Eisele, a spokeswoman for Whitehouse Station, N.J.-based Merck, wrote in an e-mail that the company is reviewing study.

“The mechanism for the possible cardiovascular benefit of raising HDL cholesterol remains under investigation,” Eisele said. “We await the results of our ongoing studies to learn more about HDL and other lipid markers as targets of therapy.”

The treatment being developed by Lilly, called evacetrapib, boosted HDL by as much as 129 percent and lowered bad cholesterol as much as 36 percent, in a trial reported in November at the American Heart Association meeting.

Lilly spokeswoman Christina D. Gaines said she couldn’t immediately comment on what implications The Lancet study would have on the company’s development efforts. She said the drugmaker is scheduled to begin final-stage testing on its HDL medicine in the second half of the year.

Nissen, the chairman for Lilly’s late-stage test of evacetrapib, said the finding in The Lancet hasn’t changed plans for studying the drug.

Both Merck and Lilly’s drugs boost HDL by blocking a molecule called CETP.

The Lancet study isn’t the first to question the effectiveness of HDL medicines. Roche Holding AG, based in Basel, Switzerland, abandoned development of its experimental HDL booster, dalcetrapib, after a late-stage study showed the drug wasn’t providing a benefit. Abbott Laboratories’ drug Niaspan also failed to show any benefit in reducing heart attack and strokes in a study released last year.

The Lancet study’s authors said their data suggests there’s no guarantee the drugs will make a difference.

“Interventions (lifestyle or pharmacological) that raise plasma HDL cholesterol cannot be assumed ipso facto to lead to a corresponding benefit” on heart risk, the authors, led by Sekar Kathiresan, a researcher at Massachusetts General Hospital in Boston, wrote in their report.

Steve Humphries, a researcher at University College, London, wrote in an editorial accompanying the Lancet report that research on good cholesterol’s effects on the heart needs to continue, despite the finding.

“Even if HDL cholesterol concentration is not validated as a causal factor, further investigation into the mechanisms of HDL cholesterol and its function in coronary heart disease is warranted,” Humphries wrote.