Wednesday, January 23, 2008

More Questions on the Value of Statins

Statins, (technically known as HMG-CoA reductase inhibitors) form a class of lipid-reducing drugs which are prescribed to reduce the so-called "bad" low-density lipoprotein (LDL) cholesterol levels in the blood of people with or who are believed to be at risk of cardiovascular disease. Cardiovascular disease is the single biggest killer of all people with diabetes (type 1 and type 2), so as a group, patients with diabetes have long been assumed to have the same risk as someone who has already had a heart attack.

For those of you who aren't familiar with them (or having been living in a cave for the past decade), statins are perhaps the drug industry's biggest category of blockbusters (meaning annual sales are well over $1 billion for each drug) and include such drugs as atorvastatin (Pfizer's Lipitor), fluvastatin (Novartis' Lescol), pravastatin (Bristol-Myers Squibb's Pravachol), rosuvastatin (AstraZeneca's Crestor), and simvastatin (Merck's Zocor, which is now widely available as a generic since its patent expired in June 2006). The drug industry has made a fortune off these drugs, and they are among the most widely prescribed medications on earth. In fact, BusinessWeek reported that statins are the best-selling medicines in history, used by more than 13 million Americans and an additional 12 million patients around the world, producing $27.8 billion in sales in 2006.

Of course, we have also seen a pattern emerge recently, whereby the drug industry tends to release only studies which show a benefit to their drugs, while studies which do not show a clear benefit are seldom (if ever) published. I wrote about this last week (see here for that article). No doubt, the statins fall into the same pattern (at least when they were launched a number of years ago), although truthfully, this drug category has seen far more objective research than most others, so it's now easier to sort fact from fiction when it comes to statins.

But in people with diabetes (both type 1 and type 2), there has always been some question whether there was any real benefit, or whether doctors were simply prescribing these pills without having sufficient evidence of incremental benefit in people with diabetes who are already at at increased risk for cardiovascular disease because of diabetes (although the risks are different in both type 1 and type 2, it is nevertheless a risk in both groups) -- often at considerable expense. I have already called attention to the fact that there needs to be a separate cardiovascular risk model in people with type 1 diabetes because there is not currently a cardiovascular risk model exclusively for this group in spite of the fact that heart disease remains the single biggest killer for them as a group. But he real question was whether statins provided any incremental benefit over the population at large?

Recently, a large meta-analysis was conducted looking at the results for nearly 20,000 patients with type 1 or 2 diabetes, and the conclusion was that all-cause mortality decreased by 9% with every 1 mmol/L decline in LDLs, the international Cholesterol Treatment Trialists' Collaborators reported in the Jan. 12 issue of The Lancet. This means statins for all adults with diabetes, right? That is certainly what the media is telling everyone. Not so fast.

While the supposed benefits of statins have been well-established, another fairly recent study also shows that taking statins destroys your muscle to at least some degree, which also includes the heart as one of the most important muscles in the body. Some bloggers find the way statin drugs have been marketed to be a scam. While I am not big on conspiracy theories, I do think the supposed benefits have been pushed without the same consideration given to the risk or expense.

Something else to consider: last week, in a cover story, BusinessWeek cast further doubt on the benefits of statins for the general population. That article singled out Pfizer's Lipitor, noting that in a 3 1/3 year study, the drug reduced the rate of heart attacks from 3% to 2%. In other words, to prevent a single heart attack, 100 people needed to take the drug for more than 3 years, prompting some scientists to suggest that patients who don't have heart disease don't really need statins.

BusinessWeek reported that drug companies made "everyone with high cholesterol think they really need to reduce it," according to Dr. Bryan A. Liang, who directs the Institute of Health law Studies at the California Western School of Law.

The reality is that the LDL cholesterol itself is not "bad", but how and where the cholesterol is being transported, and in what amounts over time, is what causes adverse effects. And not all people with diabetes have the same risk. Certainly many do, particularly those who are overweight and have type 2 diabetes may have significantly increased risk because their lipid profiles are impacted.

Diabetes in Control notes that "In type 2 diabetes, triglyceride levels are frequently elevated, and HDL cholesterol levels are suppressed. However, in type 1 diabetes, HDL cholesterol levels are generally normal or even elevated. Meanwhile, LDL cholesterol levels among patients with both type 1 and type 2 diabetes are frequently reflective of those of the general population and are not necessarily elevated."

But those people with diabetes who do not already have heart disease may not benefit any more than people without diabetes. And we cannot not conclude that a statin should automatically be prescribed for all patients with diabetes.

"It was once believed that the mere fact of having diabetes gives a person the same risk of heart attack as a person who had a heart attack before," lead-researcher Cheung said. "We are now treating people's diabetes much better than before, and their baseline risk of heart disease is lower than before."

Cheung also said that everyone with diabetes should discuss cholesterol-lowering therapy with their doctors, but he does not think doctors should always recommend drug therapy.

The most recent meta-analysis concluded that in people with diabetes, whether they are male or female, get just as much benefit from statins as anyone else -- not more. If 1,000 people with diabetes took statins for 5 years, 42 of them would avoid heart death, heart attack, or coronary revascularization (bypass or stenting). That is an improvement, but not a major one, and it comes at considerable expense to patients and/or their healthcare providers.

The reality is that statins may provide benefit for some, but the drug has almost certainly been over-prescribed, and the benefits may not be worth the huge expense for everyone. Generics are helping with the cost, and should continue next year. Once again, I will point to a particular posting from fellow d-blogger Ryan Bruner, who so eloquently wrote "I don't need no stinkin' statins!" Nor we should not conclude that everyone with type 2 diabetes needs a statin. Some may, but that needs to be evaluated relative to their risk of heart attack, not automatically prescribed. We need to be a bit more cautious in prescribing drugs among those who don't need them. This wasteful habit has cost our healthcare system (or rather the lack thereof) billions unnecessarily, for a benefit has not been proven conclusively.

3 comments:

Jenny said...

Scott,

What hasn't been mentioned in the otherwise excellent discussion provoked by Business Week's upcoming issue is that cholesterol levels have never accurately predicted heart attack for anyone, but there IS a blood test that does: A1c.

And further testing is showing that it is the post-prandial component of A1c that seems to be the most significant. (Details at Blood Sugar 101 - A1c Predicts Heart Attack

Instead of spending a fortune for a drug that gives people over 65 dementia wouldn't it be nice to help people get better post-prandial numbers using effective insulin regimens?

You could pay for a lot of CGMSes with the money NOT spent on statins.

Anonymous said...

The meta analysis did not include the most recent NEGATIVE studies--4D, ASPEN and CORONA, small trials, unpublished trials, or trials published in languages other than English.
May also behoove all of us to remember that the meta analyses on all the HRT studies were positive for their association with decrease in breast cancer and heart disease in women. Only with randomized, double blind trials did the truth come out.......

Leah said...

I feel the same way about ACE inhibitors. Although cheaper than statins, there is still an expense involved, and although they are relatively safe they still carry adverse affects - including KIDNEY DAMAGE! I truly feel like a type 1 patient does not need an ACE inhibitor until they start showing macroalbuminiuria, or microalbuminuria with other risk factors such as HTN. But to put all type 1s on ACE inhibitors? Waste of money.