New Delhi, Sept. 2: New studies have injected uncertainty over the safety and efficacy of a combination of two drugs prescribed by doctors as a cholesterol-reducing cocktail in many countries, including India.

An international study released today has shown that cancer occurred more frequently among patients who had received a combination of simvastatin and ezetimibe, than among patients on placebo — sham treatment.

Both simvastatin and ezetimibe help lower cholesterol, and reduce the risk of heart attacks and strokes. Doctors in India estimate that between 10 per cent and 15 per cent of the adults in metros with diabetes or at risk of heart disease need these drugs.

In the study involving 1,873 patients, doctors detected cancer in 105 who had received the drug combination compared with 70 who got the placebo. The increased cancers in the treatment group was “unexpected and requires further exploration,” Ann Rossebo from Aker University Hospital Oslo (Norway) and her colleagues said in the New England Journal of Medicine .

The US Food and Drugs Administration (FDA) said it was probing a possible association between the use of the simvastatin-ezetimibe cocktail and a potentially increased incidence of cancer. It also said a lower overall cardiovascular risk was not found with the two-drug combination.

However, the FDA has said the findings should not prompt patients to stop taking this combination or any other cholesterol-lowering drug. A detailed safety review could be expected in about six months, the agency said.

“The findings are significant and need to pass down to physicians across India,” said Anoop Misra, head of the diabetes division at Delhi’s Fortis Healthcare Hospital. “But some of us have shifted from this combination even before these results.”

The simvastatin-ezetimibe cocktail is made by at least three Indian drug-makers and sold as Simvotin EZ, Starstat EZ, and Simvas EZ, said Chandra Gulhati, editor of the Monthly Index of Medical Specialities, India, a drugs journal.

“The combination was primarily given to avoid increasing the dose of statins,” said Suman Bhandari, director of cardiology at Delhi’s Escorts Heart Institute. It is an option for patients who cannot tolerate high doses of statins. But doctors believe statins go beyond reducing cholesterol. “Statins influence some mechanisms involved in heart disease and such a combination may deny patients benefits from higher doses,” Misra said.

Gulhati said the combination was already a source of concern. “It is not wise to use a combination of drugs when both have the potential to cause a severe muscle injury,” said Gulhati. Both drugs carry the risk of a condition called rhabdomyolysis — muscle breakdown.