Study adds fuel to controversy about whether cholesterol-lowering drugs benefit low-risk individuals

Statins (medicines used to lower cholesterol) were famously touted as “the new aspirin” in 2001 — a drug that almost every middle-aged person should take to prevent heart attacks and stroke.

In fact, as I reported here last year, one group of cardiologists has even proposed that statins be handed out like condiments at McDonald’s.

What a difference a decade can make in medicine. We now know that the risks of daily aspirin (most notably, intestinal bleeding and hemorrhagic stroke) may outweigh the benefits in many people. And some researchers are coming to similar conclusions about statins.

The latest study to cast doubt on recommending statins routinely to people without a history of heart disease was published last week by the highly respected and independent Cochrane Collaboration. Here’s Boston Globe reporter Deborah Kotz’s summary:

The review, which analyzed 14 [randomized controlled] trials involving the use of statins to prevent heart disease in low-risk patients, found only ‘limited evidence’ that the drugs provide significant benefits, especially in women, and urge that ‘caution should be taken when prescribing statins’ to prevent heart disease.

The cholesterol-lowering drugs – which include atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin (Zocor) – have clearly been shown to reduce heart attacks, strokes, and deaths in higher risk patients such as those with diabetes or established heart disease. And they have minimal side effects.

In fact, the American Heart Association recommends that low-risk patients with high cholesterol consider taking a statin if lifestyle changes, such as increased exercise or weight loss, don’t work to bring cholesterol levels down.

But the Cochrane review study — written by British researchers — calls that practice into question, highlighting ‘shortcomings’ in studies that found clear benefits in anyone who took statins to lower high cholesterol levels.

Most studies industry-funded
As MedPage Today reporter Crystal Phend reports, those shortcomings include

the fact that eight of the 14 randomized controlled primary prevention trials of statins analyzed did not report on adverse events at all and more than a third of the studies reported selective rather than intent-to-treat outcomes.

Furthermore, … two of the larger trials were stopped prematurely at a point when the benefits may have been overestimated; the populations studied were overwhelmingly white, male, and middle-age, which may not generalize to older adults or women; and all but one of the studies had some form of pharmaceutical industry sponsorship.

Even if the health benefits claimed in these studies prove true, the Cochrane review suggests that 1,000 low-risk people would have to be treated for one year to prevent one death from heart disease. That means the other 999 people would be taking on the risks and costs of the drug without the benefits. Although serious complications seem to be rare, statins do have potential side effects, most notably muscle pain. And they do have costs. Generic statins cost about $4 per month, reports Phend.

A heated response
Needless to say, the Cochrane review has instigated a quick and sometimes angry response from statin supporters. One of the most outspoken critics (quoted in both the Boston Globe and the MedPage Today stories) is Dr. Christopher Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. He told Phend that the review was “completely biased.”

Cannon wrote an editorial last fall that accompanied another meta-analysis of statin use in low-risk patients, which appeared in the medical journal Lancet. That analysis, which looked at 13 trials, concluded that statins can lower the relative risk of heart attacks and strokes in low-risk individuals by 25 percent over four years. (It also found statins raised the relative risk of developing diabetes by 9 percent.)

But — and we’re risking study whiplash here — the major finding from yet another meta-analysis of studies (11 trials), also published last year (in the Archives of Internal Medicine), appears to agree with that of the Cochrane review. It reported no evidence that statins reduced the risk of premature death among people without a history of heart disease.

Complicating the issue
As the Boston Globe points out, Cannon “has accepted research grants from statin manufacturers and served on an advisory board for Bristol-Myers Squibb, which makes the statin Pravachol.” (MedPage Today provides an even longer conflict-of-interest list for Cannon.)

Do those conflicts mean that his criticism of the Cochrane review isn’t valid? No. But they raise questions about his own possible biases. As I noted on another topic last week, the fact that data about financial conflicts of interest are now beginning to be widely reported is going to have consequences in terms of believability for doctors, researchers and others in the medical community.

Ask questions
We haven’t heard the last about the risks vs. benefits of prescribing statins to individuals at low-risk of heart disease. (There’s a lot of money at stake. Statin drugs have apparently reached $27 billion in annual sales.) In the meantime, I agree with Minnesota blogger and medical media watchdog Gary Schwitzer (HealthNewsReview): This latest Cochrane review is “an important moment … for shared decision-making,” he writes. “This is exactly the kind of issue that demands a deep discussion between patient and physician, and a clear communication of what’s known and isn’t known about the tradeoffs of benefits and harms.”