A simmering scientific dispute over statins, the cholesterol-lowering prescription drugs that rake in some $26 billion a year for their makers, heated up Monday with an exchange of published volleys that drove back the reputation of the widely prescribed medications in one area even as it advanced their stature in another.

A meta-analysis — a review of previous studies — published in the Archives of Internal Medicine found that statins do not lower death rates among patients with risk factors but no evidence of established cardiovascular disease who take them as a preventive measure. The new study would seem to be a blow both to the drugs' makers and to three-quarters of statin users — that is, those who take the drug in hopes of averting a first heart attack or stroke.

At the same time, a study in the journal Cancer suggests that for men who have undergone surgery for prostate cancer, statin use appears to reduce the chance that the disease will return.

Against the backdrop of such research, a third study released Monday characterized as "flawed" a widely hailed 2008 study that appeared to establish the benefit of the statin rosuvastatin (commercially marketed as Crestor) in the prevention of heart attack and stroke.

The third article, also published in the Archives of Internal Medicine, raised questions about the financial and professional motives of the medical researchers who conducted the highly influential study, known as the JUPITER trial. Nine clinical trials published in the last six years have found no benefit to the use of statins in the prevention of heart disease, but "the results [of the JUPITER trial] have undoubtedly propelled many healthy persons without elevated cholesterol levels onto long-term statin treatment," wrote the authors of the critique.

The belief that statins lower the risk of a heart attack or stroke has helped make them the second-most-commonly prescribed class of drugs in the United States, behind antipsychotic medications.

Both studies published in the Archives suggest that statins' effectiveness in this area has been limited, at best, to preventing nonfatal attacks, while failing to budge the rates of fatal ones. The first, an analysis of 11 clinical trials that included a total of 65,229 patients, found that among patients who were considered at high risk of heart attack or stroke but who had not had one, statin therapy did not lower the risk of death.

Reaction to those studies underscored the rift that statins' widening use has prompted among physicians and researchers. Dr. Beatrice Golomb, a researcher at UC San Diego who is tallying reports of statins' side effects, said the thrust of the studies "supports what we should already have known — that for patients without established heart disease, statins are more risky than helpful."

Cleveland Clinic cardiologist Dr. Steven Nissen defended the use of statins in the prevention of heart attack and stroke for some patients. He also decried what he called an "ad hominem attack" on the reputations of the JUPITER trial's lead researchers — scientists he described as "eminent," "legendary" and "above reproach."

"We know that in the right patients, with the right reasons, statins can reduce a first heart attack," Nissen said. "Should they be put in water? Absolutely not. But there was definitely a reduction and it was definitely sizeable in the right people."

Editorializing in the Archives, Dr. Lee A. Green of the University of Michigan acknowledged that physicians faced with advising their still-healthy patients on the use of statin medications "really must admit that we do not know" what their best course should be. But the research that will inform those consultations in the future, Green wrote, "must be free of incentives to find any desired answer."