Published in the January 2004 issue of Today’s Hospitalist
Statins are among the most underprescribed medications for their primary use: lowering cholesterol to cut the risk of cardiovascular disease. But that’s only part of the statins story. Studies have suggested that statins may be useful in treating an array of other health problems, including osteoporosis, breast cancer and even Alzheimer’s disease.
Hospitalists, however, may be particularly interested in another potential application. Last spring, researchers from Europe and the United States published a provocative study in the journal Circulation hinting that the drugs could play an important role in reducing cardiovascular complications arising from surgery.
The Circulation study, led by Don Poldermans, MD, an internist at Erasmus Medical Center in Rotterdam, Holland, found that patients already taking statins at the time of surgery had nearly an 80 percent lower risk of heart-related morbidity and mortality than individuals not using the drugs.
Of course, lower cholesterol in the group taking statins could have been a factor in those results. But the statin advantage held even after researchers examined patients with similar total cholesterol levels. That, Dr. Poldermans says, suggests that something other than blood fats is at work.
Questions about timing
In theory, experts say, there’s good reason to suspect that statins might have short-term, circulatory effects that could reduce cardiovascular complications related to surgery. Research has shown that heart attack patients who start taking statins while still in the hospital suffer fewer heart attacks and strokes in the ensuing weeks than patients who begin taking them after discharge.
Why? The leading theory is that statins soothe inflammation of the blood vessel lining. However, the drugs’ ability to bring down low-density lipoprotein takes much longer, suggesting a possible split between their short- and long-term action. For now, Dr. Poldermans says, it’s hard to know what the optimal time frame might be for prescribing statins to surgery patients.
On the strength of their retrospective study, Dr. Poldermans and his colleagues have been giving statins to patients scheduled for vascular surgery. To qualify, patients must be diabetics or have high cholesterol. Treatment typically begins 30 days before surgery and continues after the operation. Dr. Poldermans’ group has been using fluvastatin, sold as Lescol by Novartis, which the researchers feel reacts less with other drugs than do other statins on the market.
“So far, more than 100 patients have undergone the pilot therapy at Erasmus,” Dr. Poldermans says. “Their experience will provide data that we hope will paint a clearer picture than the retrospective evidence.”
Lee Fleisher, MD, of Johns Hopkins Medical Center in Baltimore, worked with Dr. Poldermans’ group on the Circulation study. Dr. Fleisher believes the key to statins’ perioperative benefit involves vulnerable plaques.
These are the vascular equivalent of a hanging chad, a weak spot in the vessel wall caused by inflammation associated with atherosclerosis. Surgery of any kind “but particularly cardiovascular surgery “stresses vulnerable plaques and weakens them further.
What’s more, the perioperative period is marked by excessive blood clotting, which puts even more stress on trouble spots in vessels.
“If you add those together, you could get a very unstable plaque,” Dr. Fleisher says. Statins may protect vulnerable plaques from this one-two punch during and after surgery, he adds, helping them weather the trauma.
Beta-blockers already appear to perform the same role, perhaps for as long as a year after surgery, he notes. The problem is that researchers still haven’t answered several critical therapeutic questions: How far before surgery should you start a patient on beta-blockers? What’s the minimum amount of ramp-up time the drugs need to be effective? And what happens to patients who take beta-blockers long-term?
Add to that list other key questions, Dr. Fleisher says: If we get the beta-blockers right, will statins produce an added benefit? Or will the benefits of statins be drowned out completely “and not worth the added expense?
Too soon to tell
Several researchers in the United States, including Dr. Fleisher, have proposed randomized trials of perioperative statin use. To date, however, those trials have not yet begun.
As a result, experts say it’s still early for this potential hospital application of the cholesterol-busting drugs.
Emile Mohler III, MD, director of vascular medicine at the University of Pennsylvania Health System in Philadelphia, calls the retrospective evidence of a perioperative benefit of statins “impressive.” But he is quick to add that it’s far too soon to tell if that early promise will be borne out in more definitive trials.
“There’s still an unacceptably high rate of heart attacks in patients who undergo surgical procedures who have a history of cardiovascular disease,” says Dr. Mohler, who estimates the odds of such morbidity and mortality at about 10 percent. Beta-blockers have reduced this risk, but not to zero. That means there is still plenty of room for improvement, he says, and for new drugs to help back up beta-blockers.
At the very least, statins have the dual virtues of being approved by the FDA and being relatively safe. “If the prospective studies prove the retrospective studies true,” Dr. Mohler says, “then I think statins would be something you could recommend routinely” in the hospital.
Lee Goldman, MD, chair of the department of medicine at the University of California, San Francisco, says future studies of statins’ perioperative use are “very worthy” of attention. “I think it’s an interesting and promising hypothesis–which right now is not as well-developed as the hypothesis for the use of estrogen to prevent heart disease in post-menopausal women.”
He is quick to point out that he’s raised the issue of hormone replacement therapy (HRT) deliberately. Despite piles of observational data and reasonable theories, HRT fell flat in randomized, controlled trials, he points out.
“We had good nonrandomized evidence” that HRT would reduce heart problems in the women who took it, Dr. Goldman notes. “But it still didn’t work.”
That’s not to say that statins might not one day prove effective in surgery patients. “It may well be true,” Dr. Goldman points out. “But for hospitalists to start everyone on a statin pre-op would be premature.”
Adam Marcus is a freelance writer specializing in health care. He lives in New York.