Cardiologists at a conference in Chicago last week came away voicing concerns over the benefits and safety of Vytorin and Zetia, two of the most widely prescribed medications developed to control cholesterol. The companies who make them, Merck and Schering-Plough, earned about $5 billion in sales last year. Four million Americans are thought to take them.

Another drug manufactured by Merck, Singulair, prescribed for asthma and allergic rhinitis, is the subject of a recently announced FDA probe into its safety after a link to dangerous mood swings, suicidal thoughts and behaviors, and suicide itself have been reported. Several years ago, another Merck-manufactured drug, Vioxx, was pulled from the market after increased risk of heart attack and stroke was reported in patients taking that medication.

The concern with Vytorin and Zetia stems from the fact that there has been no conclusive outcome study done on either of the drugs. An outcome study typically produces reliable evidence of the beneficial, or harmful, effect of the particular drug under investigation. Such a study involves at least 10,000 patients, requires several years of clinical study, and is very expensive.

After Zetia had been on the market for four years, Merck and Schering-Plough began an in-house outcome study comparing people taking Vytorin to those taking Zocor, another cholesterol-lowering drug. That trial began in 2006 and was originally planned to reach conclusion in 2011 but the drug makers announced last Friday that the trial would continue into 2012 at least, with the possibility of extending even further into the future.

Zetia’s potential cholesterol-lowering properties come by blocking the absorption of dietary cholesterol in the intestinal tract. Another class of cholesterol-lowering drugs, statins, work by preventing the liver from producing cholesterol. Vytorin combines Zetia with a statin, Zocor.

The statins Zocor and Lipitor have been proven in outcome studies to effectively reduce the level of LDL cholesterol in the bloodstream, thereby lowering the patient’s risk of heart attack and stroke. LDL cholesterol is considered the harmful form and an excess of it can increase the risk of stroke and heart attack.

At the Chicago conference, the annual meeting of the American College of Cardiology, the full results of a short, two-year, clinical trial of Zetia and Vytorin were revealed. It’s this study, which revealed that there is no evidence of reduced cholesterol levels in patients taking the drugs but there is the possibility that taking them might have actually sped up the accumulation of dangerous fatty arterial plaques instead, which sparked the doctors’ concerns.

One cardiologist present at the conference expressed concern that prescribing these drugs at this time means doing so without hard evidence of their beneficial effect. Another advised his colleagues to prescribe these drugs only as a means of last resort. Still another said that knowing how a drug works on cholesterol isn’t the same as knowing how the drug works on the patient.

In a Sunday editorial, the prestigious New England Journal of Medicine concluded that Zetia and Vytorin may not work after all and should be restricted for use only as a last resort.