A lot of news outlets including AP yesterday and the NY Times today, are fronting an important study being published in the medical literature touting the expanded use of at least one company's Statin (lipid lowering) drug for preventing heart attacks and strokes.
However, some caution is warranted.
Below, I offer below an explanation in plain language that hopefully will be helpful to the community in explaining the truth and cautionary notes behind the hype (and yes there are health politics and policy implications):
Background:
- About 450,000 Americans will die of heart disease, which is the leading cause of death for both men and women.
- In addition to blood cholesterol levels, people with increased levels of CRP a marker of inflammation, have a higher risk for cardiovascular events.
- About half of all heart attacks and strokes occur in apparently healthy people who had pretty good levels of the "bad" LDL cholesterol. Some of these people are identifiable by having bad levels of CRP and the new "spinoff" hsCRP test.
- Statins are known to lower CRP levels, in addition to cholesterol levels.
The New Study:
The new study shows that one of the more controversial and less preferred of the cholesterol-lowering drug, appears to protect against heart attacks, strokes and death in people who do not have high cholesterol, but did have another risk factor, that being did have high levels of C-reactive protein (CRP), a marker for the inflammation process which is implicated heart attacks and strokes and related diseases.
The study randomized almost 18,000 people - men 50 and older and women 60 and older, with no history of cardiovascular disease, no diabetes and no uncontrolled hypertension, with LDL cholesterol levels less than 130 milligrams per deciliter (130 is considered "borderline high") and CRP levels of 2 milligrams per liter or higher (considered average risk) to take 20 milligrams of Crestor (rosuvastatin) daily or a placebo.
The Positives:
- The blood test markers were reduced - LDL levels by 50 percent and CRP levels by 37 percent.
- Actual disease events were also reduced. This is important because too many studies only make claims based on the markers for disease and not real disease outcomes.
- There was a 44 percent reduction in all cardiovascular events including heart attack, stroke and death.
Compared to Placebo, the group receiving the drug had:
- Heart attacks cut by 54 percent.
- Strokes reduced by 48 percent.
- The need for angioplasty or bypass was cut by 46 percent.
- 20 percent less likely to die from any cause.
That sounds great, BUT...
The Caveats:
The big immediate caveat is that those seemingly large percent reductions in disease, are actually a lot smaller then it seems when put into terms of putting a large number of healthy people in the population on the drug. This is known as the problem of the "Number Needed to Treat."
- The real bottom-line is that about 120 people would have to take Crestor for two years to prevent a single heart attack, stroke or death.
To repeat: 120 people have to take the drug for two years, to prevent one heart attack, stroke or death.
- Over 5 years, out of 100 people like those in the study, 8 would get would get heart attacks, strokes, need surgery or die if they did not get the drug; compared to 4 out of the 100 if they do take the drug every day for those 5 years.
- It is estimated that 7.4 million Americans, or more than 4 percent of the adult population, are like the people in this study. Treating them all with Crestor would cost $9 billion a year and prevent about 30,000 heart attacks, strokes or deaths. That's out of the 450,000 cardiovascular deaths per year, or still just 6.7%.
The above is the sort of population-based statistics that we use in what is called "Evidenced-Based Medice" (EBM), that the drug company hype does not report. It is part of the problem underlying the rise in cost of medical care.
- A note of caution: some studies in the past have NOT found the association with hsCRP and cardiovascular disease. More studies are coming.
- The company that make the drug, AstraZeneca, paid for the study, and the authors have been paid consultants for the company and other Statin makers. The better news articles had no trouble finding qualified physicians raising caveats, but those tended to be people not being paid by the drug company.
- The drug studied, Crestor, also has the highest rate among statins of a rare but serious muscle problem and other side effects. The company has been anxious to justify its being kept on the market.
- A co-inventor on the patent for the special high sensitivity CRP (hsCRP) test led the new study. Obviously he has a stake in this new hsCRP test becoming more widely used. It currently costs about $90.
- More people in the Crestor group had an abnormal rise in blood-sugar levels including full blown new diagnoses of diabetes. If many more now healthy people start taking the drug, we will likely see more about the side effects as well as the possible benefits.
- It is unclear which other Statins, including those which are available as much less expensive generics and which also have less side-effects, may provide the same benefit. Again, the people not affiliated with this particular drug company suggest that at least some of the other statins are likely to have the same effects.
As the editorial that accompanies the journal article points out:
Everybody likes the idea of prevention. We need to slow down and ask how many people are we going to be treating with drugs for the rest of their lives to prevent heart disease, versus a lot of other things we're not doing" to improve health.
As I would add:
- I kinda hate in principle to treat with massive population-wide drug use, what remains to a great extent a lifestyle disease.
- Typically when the use of a drug becomes widespread, the benefits turn out to be a little less and the side effects a little bit more common than initially thought. Often new side effects turn out. It can take several years, of population wide use to figure this out.
- My best guess at this time, is that there is a real net benefit, and that at least some of the other cheaper and safer Statins would/will provide the same benefit. We will probably be prescribing statins to a wider range of folks in the near future. But caveat emptor still applies.
Update:
- Thanks for rec list.
- For the record, I am on a statin myself for standard cholesterol reasons. Also multivitamin, calcium and fish oil pills. I eat more healthy than most Americans but am not as strict as I should be and most of all I don't exercise enough. See #6 below.
- In addition to the hsCRP going down, the LDLs also went way down. Hard to say which, or both, is related to the decrease in disease.
- Per my Caveat #3 & #9, UndercoverRxer points out that the study drug Crestor costs $1200/yr compared to statins available as generics at < $100 per year. Likely that other statins provide similar effect, that that this is a class effect, but don't know for certain, and there may be some drug-to-drug varation. The problem is that no such study is out yet, and any quickly done study will be using markers (hsCRP) and not real outcomes. I hope the other companies have similar studies in the pipeline. But their incentive is less when it's gone generic. This is part of the problem with how drug studies are done. Too much dependence on the drug companies. Too little truly independent research. Need true FDA-done studies comparing look-alikes, to see where variations if any really are.
- Similarly per my caveat #9 and plf515 below: On the one hand there are class effects, all statins similar (but not identical). On the other hand, there is some drug-to-drug variation within the class/theme, with slight differences, more or less effects on maybe on LDL, HDL, anti-inflmatory hsCRP effect, and side-effect profiles. And there are also some individual person-to-person variation, wherein one statin may work better than another in different people. But such variation is probably overtouted by the drug comapanies to justify the plethora of look-alikes. Again, because there is no serious money to do independent head-to-head studies comparing look-alikes, we do not know about such variation as much as we need to. This is actually a matter of federal policy, what Congress mandates and funds the FDA (or NIH, or AHRQ) to do.
- Diet & Physical Activity: I am not going to endorse specific brand name diets, but my quick version of a healthy diet is: "Fish, Broccoli & Beans". Also, physical activity to raise your heart rate and break a sweat for at least 15 minutes a day or 30 minutes 3 times per week. Now... go do as I say, not as I do. ;)