Bone Drug May Boost Statin's Heart Benefits

A bone-strengthening drug sometimes used to treat osteoporosis may boost the cholesterol-lowering power of statins, according to preliminary research presented today at an American Heart Association meeting in Chicago.

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By Lynne Peeples

THURSDAY, April 28, 2011 ( — A bone-strengthening drug sometimes used to treat osteoporosis may boost the cholesterol-lowering power of statins, according to preliminary research presented today at an American Heart Association meeting in Chicago.

Researchers in Canada and Japan found that the combination of a statin and a bisphosphonate appears to work better than a statin alone at slowing the buildup of cholesterol-filled plaques in the aorta, the major blood vessel that carries oxygen-rich blood from the heart to other parts of the body.

Plaques in the aorta gradually thicken the wall of the artery and can impede blood flow. (This process is known as atherosclerosis.) If the plaques burst, the resulting blood clots can cause heart attacks and other serious heart problems.

Statins are usually effective at keeping atherosclerosis in check, but the drugs are far from perfect, says the lead author of the study, Tetsuya Kawahara, MD, of the University of Calgary, in Alberta. While statins can reduce plaque buildup in the section of the aorta that passes through the chest (the thoracic aorta), they appear to have little effect on plaques in the abdominal section of the aorta.

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Dr. Kawahara and his colleagues suspected that a bisphosphonate known as etidronate (Didronel) might boost the efficacy of statins. Previous research has suggested that etidronate may interfere with the buildup of calcium deposits that contribute to the narrowing and hardening of arteries.

To test this theory, they randomly assigned 251 older adults with high LDL, or bad cholesterol, to a daily regimen of atorvastatin (Lipitor), or atorvastatin plus 400 milligrams of etidronate. After two years, the researchers compared changes in plaque buildup by using magnetic resonance imaging (MRI) to measure the thickness of the blood-vessel walls in different regions of the patients' aortas.

In the thoracic aorta, the thickness of the vessel wall shrank by 13% to 15% in both groups. In the abdominal aorta, by contrast, the wall thickness shrank by 12% in the combination group and just 1% in the statin-only group.

Further, only 1 of 128 patients on the combination experienced a heart attack or other cardiac event over the two years, compared with 6 of 123 patients in the other group.

The differences in wall thickness seen in the study might be due to the different types of plaque in each section of the aorta, Dr. Kawahara explains. Fatty plaques are common in the thoracic aorta, while calcified plaques are common in the abdominal aorta.

The findings are important, says Robert Shamburek, MD, a researcher at the National Heart, Lung and Blood Institute, in Bethesda, Md. But he cautions against drawing firm conclusions from the study because of the small number of patients and the relatively short duration.

"It's too early to go to a doctor and ask for this combination if you don't have an indication for the osteoporosis drug," he says.

Dr. Shamburek, who was not involved in the new study, also points out that the 20-milligram dose of atorvastatin used in the study is far lower than what is typically prescribed in the U.S., which makes it hard to judge how the findings might translate into everyday practice.

Still, Kawahara predicts that if a large-scale clinical trial can confirm the benefit, the combination of etidronate and a statin could be commonly used within five or six years.

Etidronate and a similar drug, clodronate, are the only bisphosphonates that are believed to fight artery calcification. They belong to an older class of bisphosphonates and were not included in the Food and Drug Administration's 2010 warning about a possible increased risk of thigh-bone fractures in people taking newer bisphosphonate drugs.

Unlike newer bisphosphonates, etidronate is not primarily used to treat osteoporosis. Though doctors sometimes prescribe it off-label for that purpose, it is mainly used in hip-replacement patients and people with the bone condition known as Paget's disease.

Dr. Kawahara presented the findings at the American Heart Association's annual meeting on Arteriosclerosis, Thrombosis, and Vascular Biology. Unlike the studies published in medical journals, the research has not been thoroughly vetted by other experts.

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