Atherosclerosis — the scarring of blood vessels that leads to heart attacks and strokes—remains atop the leader board for the most common cause of death in people over 65. Drugs called statins (Crestor, Lipitor and Zocor, to name a few) are a critical part of the treatment of atherosclerosis, reducing cardiovascular mortality by around 30 percent. That’s a big number in fighting such a serious disease, but of course, it can’t be that simple and it isn’t.
You can’t benefit from a medication that you’re not taking, and as many as 20 percent of people who start on a statin end up stopping, primarily due to complaints of muscle aches.
The Problem With Statins
A study in the Journal of the America College of Cardiology looked back at over 100,000 Medicare patients who were started on a statin after being diagnosed with atherosclerosis of the coronary arteries. Over about a two-year period, a remarkably small number of those patients — just 1.65 percent — couldn’t tolerate taking a statin because of muscle aches. Why such a small number? Either this trial sampled an exceptionally grizzled and stoic crowd (any of the lead actors in The Expendables) who mostly chose to ignore the pain, or, as was actually the case, the researchers chose a more stringent definition of “statin intolerance.”
They then compared the 1.65 percent of patients who were statin-intolerant with the 52 percent of patients who managed to fairly consistently take a statin. After accounting for variables that might skew the outcomes, the researchers found that those who couldn’t tolerate a statin had a 50 percent higher risk of having another coronary heart disease event. An “event” was defined as either a heart attack (myocardial infarction) or a near heart attack that led to either angioplasty (opening a blocked artery via a catheter) or coronary artery bypass surgery.
Fewer Heart Problems, but Not Longer Lifespans
The statins did what we thought they would do. They stabilized the scarring process that results in atherosclerosis and lowered the likelihood of more heart problems, and the people who couldn’t take them couldn’t get that benefit. No surprises here — except for one thing: taking a statin didn’t seem to lengthen lifespans.
Unless the muscle aches are severe enough to cause significant muscle injury, there is no lab test that can clinch the diagnosis.
The statin users were less likely to die of heart disease, but then something else got them (cancer is No. 2 on the mortality leader board). Perhaps this was because the analysis involved an older group of patients, and interventions late in life tend to have a lower payoff.
How to Define ‘Statin Intolerance’
As an accompanying editorial by well-known Cleveland Clinic cardiologist Steven Nissen points out, statin intolerance is a vexing issue, beginning with how to define it.
Unless the muscle aches are severe enough to cause significant muscle injury — what doctors call myositis or rhabdomyolysis — there is no lab test that can clinch the statin intolerance diagnosis. But statins and muscle aches are now so thoroughly linked via word of mouth, and the Food and Drug Administration-mandated voiceover disclaimers on TV ads, that many statin users have come to expect they will have muscle aches, what’s been termed the “nocebo effect.” A placebo anticipates a positive effect inconsistent with science (“this antibiotic is sure to kill off the virus that is causing my bronchitis!”) and a nocebo anticipates a negative effect.
The Nocebo Effect
Results from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that the nocebo effect is a genuine phenomenon.
The trial randomized over 10,000 patients to receive either a low dose of atorvastatin (Lipitor) or a regular dose of a placebo. Three years into things, the trial had to be stopped on ethical grounds: those taking atorvastatin had a 36 percent lower chance of either dying from a heart attack or having one that they survived.
The patients who had been taking a placebo were then offered a statin (one-third declined) and enrolled into another branch of ASCOT for another two years.
During the initial three years of the study, where the patients didn’t know whether they were taking a statin or a placebo, there was no statistically significant increase in the reports of muscle aches. But when patients knew they were taking a statin, muscle-related complaints shot up by 41 percent. Ouch.
True Intolerance, or Nocebo Effect?
Unfortunately, this latest research only cements what we already know about the benefits and tolerability of statins, when we could sorely use a jackhammer.
We’re a bit stuck. We know which patients can benefit from being on a statin, but we don’t have a great way to tell the difference between true statin intolerance and the nocebo effect.
In the meantime, if you’re in the unenviable position of needing a statin but not being able to stand one, you’ll need to work through the options with your doctor — who might well use this Statin Intolerance Tool developed by the American College of Cardiology.
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