On Wednesdays, I try to write on a topic of exercise and health.
If you exercise but still have high cholesterol or other risks for heart disease, you may be interested in a new study from my old medical school proving ground–Hartford Hospital.
The deftly named STOMP trial looked carefully at the effects of statin drugs on muscular strength and endurance.
The Background:
Muscular complaints related to statin drugs are a common occurrence. I see it often. The incidence of muscle-related issues (pain, weakness, or enzyme abnormalities) range from 1% to 25%. Estimates from clinical trials of statin drugs likely underestimate the real world incidence of the problem. Observational trials, which look back at general populations, mirror what most doctors will tell you: that the incidence of muscle symptoms on these drugs approaches 10% or higher. It’s a vexing problem because statin drugs offer selected patients significant protection from cardiovascular events.
For exercisers, especially competitive athletes, muscle function is something that we hold dear. We don’t want a heart attack or stroke; we’d take a drug that would lower that risk; but we cannot have—it would just be too bitter a pill—a treatment that hurts our precious muscles. For cyclists and runners alike, “bad legs” is a never event—always to be avoided.
The STOMP study:
Reed Miller has a nice recap on theHeart.org. Here’s my short summary:
Researchers randomized 468 patients to either a statin drug (atorvastatin, Lipitor 80mg daily) or a placebo. The study was double blinded. Neither the investigators nor the patients knew the treatment assignment. Patients were followed and tested over a 6-month period. This simple but elegant experiment allowed the researchers to answer their main question (hypothesis): Do statin drugs reduce muscular strength or endurance?
The findings:
- Patients on atorvastatin exhibited a small rise in CK (muscle enzyme) levels, although no subject reached the definition of muscle inflammation (myositis).
- More patients on the statin drug than placebo (40 v 29) had CK levels out of the normal range.
- Muscle pain or myalgia (strictly defined) was noted in 19 subjects on statin v 10 on placebo.
- Statin-induced muscle complaints involved the big muscles of the legs, whereas placebo-induced complaints scattered throughout the body.
- Muscular strength and aerobic performance were similar in both groups.
The conclusion:
The findings of the STOMP trial provide a degree of reassurance to patients and doctors. Although high-dose statin therapy may increase the incidence of muscle complaints or cause slight rises in muscle enzymes, these drugs do not reduce muscle strength or endurance.
My thoughts:
If confirmed in other studies, this is big news for athletes.
I found STOMP worth mentioning because I’ve always wondered whether these (potentially) life-extending drugs force an exerciser to make a choice. Does one have to trade watts, MPH, min/mile, bench press (or whatever your measure) for cardiac protection?
Of course, as an athlete, I favor such favorable results. It’s what I wanted to hear. I didn’t want to have to tell exercisers that a statin drug will make them slower or weaker.
Liking a study’s results a lot should trigger an internal warning sensation. It should cause you to talk to yourself. Am I drawn to the findings because they are sound scientifically or do they support my pre-conceived notion?
So let’s be careful not to overreach. STOMP is a small single center study done on low-risk young patients. It has significant limitations. These findings may not generalize to older and sicker patients. (Remember: it would be unethical to do such a study in older high-risk patients–as statins have proven benefit in this group.)
The major limitation of the study, however, was its short duration—only six months. Many patients prescribed statin drugs will be on them longer than six months. Will these muscle-neutral findings hold up over years or decades? That question can only be answered with longer follow-up.
And this final caveat:
Please don’t misinterpret my commentary. I am not citing this study as proof positive that statin drugs are safe. Like all medicines, statins are potent chemicals that have real effects on the human body. They have risks, benefits and alternatives. I’m not delving into whether you should take a statin drug. That should be a shared decision between patient and doctor.
JMM
Other good references:
Nice review article on Statin myopathy: A common dilemma not reflected in clinical trial
22-patient study on professional athletes with familial high cholesterol levels.
Ken Grauer, MD says
December 20, 2012 at 6:05 amThanks to Dr. John for posting this recently published from Circulation study on statins. My “take” of this article is a bit more skeptical than that which I read above. No longer having access to PubMed – my thoughts had to be based on the abstract and write-up by Reed Miller in theHeart.org. A total of 420 healthy, statin-naive subjects were given a hefty (80mg) dose of atorvastatin for 6 months. I agree with Dr. John on the GOOD news of this study – namely that for athletic, younger healthy adults – it does seem that 6-months of full dose statin use does not impair objective measure of exercise performance.
I saw a different spectrum of patients when I was in practice. It is difficult to sort out groups and conclusions from this study. I see in Reed Miller’s write-up 3 different age groups (30-ish up to 55 years or older) which really means small numbers of patients had to be in each group. The overall incidence of “myalgias” seemed to be a bit under 10% in the statin group (vs 5% in placebo) – but I don’t know the breakdown for relative proportion having myalgias among older subjects vs younger adults in this study (and given the small numbers I don’t know how conclusive that would be even if I knew the “breakdown”).
I see numerous potential conflicts of interest on theheart.org at the bottom for author relationships with various pharmaceutical companies … (sponsorship, consulting, etc.).
So the issue I saw daily in my practice was of older patients – often with other comorbidities (and on many drugs) – who complained of difficult-to-describe muscle discomfort after being placed on statin drugs – which only went away after stopping those drugs. Anecdotally – the incidence seemed a good bit more than 10% to me … Though admittedly not an easy subset to objectively study – THAT is the issue I’d like to see addressed before suggestions from a small study on healthy subjects by authors with multiple pharmaceutical ties claims “statins are safe” (with presumed intended implication in this article that widespread statin use should not be hindered by potential for adverse effects). Makes me wonder about potential financial impact of these results. The above – just thoughts from this skeptical mind …
Dr John says
December 20, 2012 at 6:34 amThanks Ken.
I agree with you on the difficulty of generalizing this trial to older sicker patients. So do the authors, I think. Here is a quote from the conclusions:
“The inclusion of younger subjects and both genders may have reduced the number of subjects with myalgia during atorvastatin treatment since subjects with statin myalgia in STOMP tended to be older and more were woman. STOMP only lasted 6 months so may underestimate the incidence of myopathic complaints during longer term statin therapy, although onset of myalgia with atorvastatin occurred an average of one month after initiation of therapy.”
A lot of athletes have come up to me on rides and said they don’t want the statin because it will make them weak. Herein lies is a ‘little reassurance.’ Whether a younger person should take a statin for primary prevention is a hotly debated topic indeed. Smart people make strong arguments for and against.
Phil says
December 20, 2012 at 1:57 pmDr. John,
Thanks for sharing. I am a 53 y/o patient of your colleague ***** and suffered an MI in 7-07 while training on my bike. In light of my CAD, dehydration was the major contributing factor that hot summer day and i still kick myself for that considering the expensive health insurance premiums I am faced with. I’ve been on 20mg Lipitor, 10 lisinopril, plavix, and ASA and within a year completed a 1/2 ironman and continue to pursue triathlons. Phil
jane says
December 21, 2012 at 5:48 pmWe’re also told that exercise reduces our risk of having heart problems and extends life expectancy, which statins do not do for many subgroups of users, not to mention functional life expectancy. For those individuals who do report that their muscle pain or fatigue is so bad that they “can barely climb stairs” and have to give up physical activities, I have a huge suspicion that (except maybe for some of the sub-70-year-old, male, secondary prevention patients) the statistical longevity hit they take from becoming totally sedentary is greater than the statistical benefit to be gained from the drug. But where can a patient who places high value on life expectancy go to get unbiased data on the subject? Some cardiologists – not you! – aggressively dismiss any concern that use of a drug may prevent someone from exercising more or eating better and thereby perhaps recovering. I’m not sure whether it is because they refuse to believe that lifestyle can be as potent as a drug, or because they refuse to believe that a heart patient engages or ever will engage in healthy behaviors.
Ken Grauer, MD says
December 21, 2012 at 6:52 pm@Jane – Please check out this link: http://www.thennt.com/statins-for-heart-disease-prevention-without-prior-heart-disease/ – It will take you to a NNT (= Number-Needed-to-Treat) piece on use of Statin Drugs Given for 5 Years for Heart Disease Prevention in Persons WITHOUT Known Heart Disease). Many of the treatments that are offered to patients by physicians might not be as readily accepted IF data was presented to patients in terms of NNT = How many patients need to take a drug or undergo a treatment in order for one patient to benefit.
The above piece re Use of Statins as Primary Prevention was written by David Newman, who I am aware of by reputation as an astute clinician/researcher. You can look up the details at the link – but 98% of patients get NO benefit from 5 years of statins – 2% have a stroke or heart attack prevented – and no one’s life was saved in the literature search they performed (at least by the statistics analyzed). This means that out of 100 patients all taking statins daily for 5 years – paying for the drug, as well as for follow-up blood tests and doctor visits – 98 are likely to get NO benefit (nada). IF you are one of the 2/100 patients who have a heart attack prevented by taking the drug – then taking the drug IS worth it – but for every patient to benefit – 49 will get NO benefit – and the drug is costly, requires much follow-up AND there is not insignificant possibility of side effects (including myalgias as mentioned). Whether the potential to get benefit vs the potential for harm/adverse effects/cost is “worth it” should be an individualized decision to be made by the patient (in my opinion). It will be for some – it may not be for others.
All that said – in my opinion, vigorous attention to lifestyle factors including healthy diet and appropriate regular exercise leading to increased fitness and weight loss to me give an otherwise healthy individual much more bang for the buck than taking a daily statin …. (This all assumes the patient is a non-smoker – since smoking cessation clearly is the most important thing to do to lower one’s risk … ).
Final Comment – The above relates ONLY to primary prevention. The benefits of statins are MUCH greater (and clearly worthwhile) in patients who have already had their heart attack (ie, as secondary prevention).
jane says
December 22, 2012 at 11:32 amDr. Grauer – Thanks! Suppose though that you are a patient who shares the doctor’s values (avoiding strokes or heart attacks, and for the secondary prevention group also extending life, are the highest values) but who is having his physical activity limited by statins. What would you use as a definitive NNT for exercise to compare to the NNT for statins, since you’re only going to be able to use one of those interventions? All large long-term studies of exercise are subject to confounding, and as far as I know, there’s no reliable estimate. Most of those studies are in people who start off healthy; what would the NNT for exercise be for a secondary prevention patient? What are the relative NNTs in women and the very old, who haven’t been shown to benefit much from statins? Even if a doctor was willing to deal with this issue, I don’t know that he would be able to provide numbers that were meaningful enough to support informed decision-making.
Ken Grauer, MD says
December 22, 2012 at 2:46 pm@Jane- The same web site that I got the NNT figure for primary prevention cited the following for secondary prevention (http://www.thennt.com/statins-for-heart-disease-prevention-with-known-heart-disease/ ) – 96% of patients with known heart disease taking a statin for 5 years saw no benefit – but 1.2% were SAVED from death; 2.6% had a 2nd heart attack prevented – and 0.8% had a stroke prevented. Incidence of side effects was similar as for primary prevention (same cost, chance for adverse effects including myalgias). Thus, there clearly IS life-saving benefit, even though the reality is that most patients taking the statin still won’t get benefit. That said – potential benefit for the few patients who DO have a positive effect is clearly significant – so I agree with general consensus that statins ARE overall a “good thing” to do for patients who have known heart disease.
That said – there still should (in my opinion) be individualizing for each patient – because true NNT vs NNH (number needed to harm) numbers may vary depending on age, sex, associated co-morbidities, and how particular patients tolerate the drugs. For some patients subject to truly bothersome muscle aches on any dose of any statin – it may simply not be worth it to take the drug. How much that patient can make up by attention to lifestyle measures without statin use is unknown. And perhaps some patients may be able to tolerate a low dose of a certain statin – which while not lowering lipids to “target” may nevertheless provide significant risk reduction at a dose that becomes tolerable. Bottom Line: NO perfect answer – each patient should be individualized, with I believe goal at maximizing patient-directed decision-making as much as is possible and desirable. Hope that helps.