The Food and Drug Administration is considering expanding the use of cholesterol-lowering statin Crestor to those who have increased levels of inflammation—but not high cholesterol. The agency moved one step closer on Tuesday after an advisory panel voted 12 to 4 (with one abstention) to approve Crestor for this expanded use, which could open the door for 6.5 million more Americans to take statins.
Experts are divided. Cardiologist Melissa Walton-Shirley, who moderates a forum on theheart.org, says she's thrilled about the expanded use. "Any effort towards prevention is admirable. With Crestor, maybe folks with inflammation, known to promote atherosclerosis, never have to develop artery plaque at all." FDA advisory panel member Charles Mouton, however, voted against the label change because, he tells me, he was worried that the drug might be promoted to the wrong people: younger folks at very low risk of developing heart disease in the near future.
Then there's that nagging risk of diabetes. The Jupiter study on which the potential label change is based found that 2.8 percent of folks in the Crestor group developed diabetes compared with 2.3 percent of those who took placebos. (That would amount to more than 30,000 new cases of diabetes if an additional 6.5 million people started taking statins.) The folks in the Jupiter trial had normal cholesterol levels but elevated levels of C-reactive protein, an inflammation marker measured via a blood test. [Here are the full details of the study.]
Experts still can't explain why Crestor would increase the likelihood of diabetes, but other research suggests that the entire class of statin drugs appears to have this downside. An October study in Diabetes Care that analyzed trials using various kinds of statins found a 13 percent increased risk in diabetes in the statin users. "What do you do if you have a drug that might be causing a small number of excess cases of diabetes but is indicated in the same population to protect them from cardiovascular disease and mortality?" says Allison B. Goldfine, section head of clinical research at the Joslin Diabetes Center in Boston. "I think it's a very interesting question." The diabetes risks, she adds, need to be weighed against the cardiovascular benefits: The Jupiter trial found that 1.5 percent of the placebo takers had a heart attack or stroke compared with 0.72 percent of the statin takers, which would come out to about 50,000 fewer heart attacks and strokes out of a potential 6.5 million extra users.
Of course, there's also the question of who would actually wind up taking statins should the new indication go through. (The FDA hasn't said when it will make a decision, but the agency usually follows the recommendations of its advisory committees.) The expanded indication would be for men ages 50 and over and women ages 60 and over who have a high-sensitivity CRP test score of 2 mg/L or above. Mouton says he's concerned that Crestor commercials and magazine ads will portray younger-looking people—making, say, an otherwise healthy 40-something woman with elevated CRP mistakenly think she needs a statin, even though her heart disease risk is extremely low.
Beyond diabetes, statins can have some troubling side effects. Women, in particular, are more likely to develop muscle pain from statin drugs, which happens in anywhere from 3 to 15 percent of users. "It feels like that really sore feeling you get two days after going to the gym for the first time and using every machine to the max," says Walton-Shirley, who developed the pains herself when she started taking a statin for her high cholesterol, prompting her to switch to a lower dose. Mild memory loss can occasionally occur, and in very rare cases the drugs can have a detrimental impact on the liver. [Here's more on the pros and cons of statins.]
Whether the benefits measured in the Jupiter study apply to any older person with an elevated CRP level remains to be seen. The folks in the Jupiter trial had an average CRP level of 4 mg/L, though those with levels as low as 2 mg/L were allowed to join. They also tended to be overweight, and many were on the cusp of developing diabetes. In other words, these are people who were already heading toward heart disease. What all this means is that should the label change go through, women with no heart disease risk factors other than an elevated CRP will need to have a long talk with their doctors about whether they fit the profile of someone who could indeed benefit from a statin.