Let’s close the chapter on statin safety


There was important news recently on statin drugs. As one of the world’s most effective and commonly used medications, statins provide great writing topics. Lots of people have high cholesterol–including cyclists. Lots of people are interested in avoiding our mostly deadly disease.

I’d like to tell you about a recently-published landmark study in the Lancet that should quell safety concerns over statin drugs.

The punch line after I tell you the study’s results are short and sweet. Scroll down if you wish. But first, statin drugs are misunderstood enough to warrant a little blog-like simplicity. Let’s start with some background.

A brief statin review

Statin drugs are best known for their cholesterol-lowering properties. The notion is simple: high cholesterol levels are associated with heart disease and stroke. Drugs that lower cholesterol figure to reduce heart disease.

For statin drugs this hypothesis proved correct–but most clearly for patients that already have heart disease or are at high risk for heart disease (diabetic patients, for example).

In a nutshell, statins are probably the most important pill a patient with heart disease can take. For these high-risk patients, the secondary prevention effect of statins are remarkable.

The statin intrigue

What’s surprising and intriguing is how statins confer benefit. It turns out that the cholesterol-lowering effect of statins is not likely how they prevent heart disease. This idea is hard to explain because statins simultaneously reduce both cholesterol levels and heart attacks. Here’s the thing though: patients at risk for heart disease derive benefit from statins regardless of their cholesterol level. Moreover, lowering cholesterol levels with non-statin drugs does not reduce heart attacks or death!

I have come to believe—and over-simplistically explain to patients—that cholesterol lowering is only a side effect of statins. Their real effect probably has to do with their ability to prevent plaques from rupturing and platelets from clumping in the inside of the blood vessel. Consider statins anti-inflammatory agents for blood vessels.

All this seems too good to be true. If these pills are as good as you say, let’s put them in the water or at least sell them over-the-counter. Heck, you can easily buy drugs that increase strokes, heart attacks, internal bleeding and even AF. Why not let patients buy a drug that has been shown to reduce heart attacks and strokes?

Well, there is a rub. Of course there is a rub; we are talking about pills here. Regular readers and most masters of the obvious know that swallowing a pill can’t solve heart problems.

Statin unknowns

Two major issues have suppressed widespread non-prescription use of statins. The first is safety and the second is effectiveness in lower-risk patients.

Let me readdress the effectiveness issue first. Though study after study unequivocally demonstrate that statins reduce heart attacks and strokes in high-risk patients, the evidence is less convincing for low-risk patients. Experts far smarter than I debate this issue and a discourse here is beyond the scope of this blog post. Suffice it to say, it’s not clear whether statins make a difference in patients with high-cholesterol but few other risk factors for heart disease. (Medical people call this primary prevention–using a therapy to prevent a problem in the first place.)

The most recent news story centers on the question of statin safety. Though these drugs remain one of the most studied and safest pills of all time, they are dogged by concerns over safety. I am not sure why this is the case, but my (admittedly anecdotal) experience holds that even educated people are frequently blinded to the benefits of statins because of exceedingly rare adverse effects. It seems a .001% chance of a serious adverse effect from the drug trumps its 25% reduction in the chance of dying from a heart attack. (Misplaced fear analogy: It’s like being scared of lightening but not potato chips).

The HPS statin studies are worth knowing about

The follow-up data from the Heart Protection Study sheds a bright light on statin safety. The mostly British researchers with the Heart Protection Study Collaborative Group have done a great deed. They continued following patients in the HPS (1997) trial for another six years after the 5-year trial was completed. Now, both doctors and patients have yet more reassuring news about the long-term use of statins.

Let me summarize what they found (you can read excellent summaries on Cardiobrief and TheHeart.org):

  • Published in 2002, the original HPS trial compared more than 20,000 patients with heart disease, peripheral artery disease or diabetes who took simvastatin 40mg (Zocor) daily to those who took placebo.
  • The results were breath-taking. Across every subgroup, including those with ‘normal’ cholesterol, patients on the statin drug suffered fewer heart attacks, strokes and deaths. Additionally, there was no evidence of an increase in liver failure, cancer or any non-heart related illness with statins.
  • Most recently, HPS investigators report on the long-term follow-up of these same patients. After the original HPS trial ended, researchers instructed patients on statins to stay on them, and control patients to start them. They then followed these two groups for 6 more years.
  • In 11 years of follow-up, the researchers found that the original benefits of the statins remained. (No further benefit was shown because equal numbers of patients were on statins).

The big news was this:

  • The incidence of cancer and non-heart related death was the same in both groups.

One can only hope that most can now agree with what distinguished experts, Drs. Payal Kohli and Christopher Cannon, wrote in an accompanying editorial:

…the long-term results of HPS suggest that the early benefit of statins is likely to be followed by a prolonged legacy period, with benefit maintained over time and that extended use of statins is safe with respect to possible risk of cancer and non-vascular mortality.

Let’s close the chapter on statin safety. Let’s mute the purveyors of misinformation.

Sure, there are some patients that cannot take statins because of muscle pain. That doesn’t mean, however, that statins cause permanent or irreversible health problems. This 11-year trial in 20,000 patients provide compelling safety results: statins do not increase the risk of death, cancer or serious non-heart-related illness.

Though I can’t answer the question of whether statins benefit low-risk patients, I now feel even more confident in saying that the long-term risks of statin drugs are not scary.

John Mandrola is a cardiologist who blogs at Dr John M.

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