Statin enthusiasts have half jokingly suggested that statins are such marvelous medications that they should be introduced into the water supply, almost like fluoride. Their argument goes that if everyone got a daily dose of statins, they could dramatically reduce the risk of heart disease, and almost everything else for that matter.
Two studies just published in the New England Journal of Medicine (and an editorial titled “Statin Strikeout”) suggest that the statin juggernaut might be losing a little steam. This research was funded by taxpayer money and attempted to determine the value of statins for people with really severe breathing problems.
In one study, nearly 900 patients with chronic obstructive pulmonary disease (COPD) were recruited to receive either simvastatin (Zocor) or placebo. They were followed for roughly 641 days. The hypothesis was that patients taking simvastatin would have fewer flare-ups (“exacerbations” or serious breathing problems), hospitalizations or deaths compared to those on placebo.
The results were disappointing. Simvastatin (40 mg daily) did not improve lung function, did not enhance quality of life, did not reduce exacerbations and did not diminish deaths. The researchers pointed out that their results contradicted previous “observational” studies that demonstrated tremendous lung benefits from statins, thereby suggesting that such epidemiological research is often unreliable. This randomized controlled trial (RCT) put the brakes on the enthusiasts who were ready to start prescribing statins to patients with COPD.
The other study was equally disillusioning. Severely ill patients diagnosed with acute respiratory distress syndrome (ARDS) were the subjects in this trial. These are patients with a life-threatening lung condition sometimes called “shock lung.” It is life threatening and can be triggered by a respiratory infection such as pneumonia. People with ARDS have trouble breathing because of terrible lung inflammation and frequently have an accompanying systemic infection. Organ system failure often follows the profound inflammatory response called sepsis. Because statins have an anti-inflammatory effect, the researchers hoped rosuvastatin (Crestor) would “improve clinical outcomes.”
Au contraire. Here are the conclusions:
“Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.”
In other words the rosuvastatin did not reduce mortality from ARDS or improve other outcomes such as fewer days on a ventilator or improved lung function. There was also some suggestion that this statin had a negative impact on both kidney and liver function, not a good outcome for patients in a life-threatening situation already.
Other Statin Strikeouts: Alzheimer’s Disease
This is not the first time that epidemiological studies had suggested statin benefits for health conditions other than heart disease. There has been a drumroll of enthusiasm for using statins to prevent or treat Alzheimer’s disease and dementia. Again, the theory was that the anti-inflammatory effect of statins would be beneficial for the brain. A number of observational studies suggested that older people taking statins might be less likely to develop dementia.
Needless to say, this sort of finding created a lot of excitement within the statin-enthusiasts community. But epidemiological research doesn’t hold a candle to the gold-standard type of research in which one group of patients gets placebo and the other gets active drug (RCTs or randomized controlled trials). One such trial was conducted with atorvastatin (Lipitor). In this study 640 older people with mild to moderate Alzheimer’s disease were randomized to receive either 80 mg of atorvastatin daily or placebo. The statin did not slow cognitive decline.
Despite this negative finding, there is growing interest in prescribing statins to prevent Alzheimer’s disease. That is why the analysis by the independent experts at the Cochrane Collaboration is so important:
“There is good evidence from RCTs that statins given in late life to individuals at risk of vascular disease have no effect in preventing AD [Alzheimer's disease] or dementia. Biologically it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. Indication bias may have been a factor in these studies however and the evidence from subsequent RCTs has been negative.”
And this from the Cochrane Database of Systematic Reviews regarding treatment of cognitive decline:
“There is insufficient evidence to recommend statins for the treatment of dementia.”
The Statin Wars Continue
Just as there is polarization in politics these days, there is growing polarization within medicine when it comes to the benefits and risks of statins. The enthusiasts are quick to point out that statins have been shown to reduce the risk of recurrent heart attacks. That is to say, once a person has diagnosed heart disease, has a stent inserted in a coronary artery or has experienced a cardiac event, statins can reduce the risk of another event or death. This is called secondary prevention. There is little controversy about this.
What is far more contentious is whether statins do anything positive for people who are otherwise healthy. Some researchers are adamant that statins work to prevent cardiac events in so-called primary prevention. Others say not so fast. The number crunchers at TheNNT.com have analyzed the available data from randomized controlled trials. Their conclusions regarding people without known heart disease:
Taking a statin for 5 years:
1) did not prevent death
2) prevented a heart attack in 1.6% of subjects
3) prevented a stroke in 0.4% of subjects
4) provided no benefit in 98% of subjects
Statin Side Effects
Some physicians are relying on randomized controlled trials to demonstrate that statin side effects are insignificant and do not exceed side effects from placebos. A recent meta-analysis (The European Journal of Preventive Cardiology (March, 2014) concluded:
“At the doses tested in these 83,880 patients, only a small minority of symptoms reported on statins are genuinely due to the statins: almost all reported symptoms occurred just as frequently when patients were administered placebo. New-onset diabetes mellitus was the only potentially or actually symptomatic side effect whose rate was significantly higher on statins than placebo; nevertheless, only 1 in 5 of these new cases were actually caused by statins.”
In other words, except for a touch of diabetes, statins do not cause muscle pain, weakness, peripheral neuropathy (nerve damage), or any of the other side effects that have been widely reported on this website and even in the medical literature. One reason that the randomized controlled trials may not have identified side effects such as muscle pain is a lack of a shared definition. A recent report in the American Heart Journal (April 10, 2014) notes that in the real world of clinical practice, muscle problems are reported by 10-25% of people taking statins.
The take home message from the New England Journal of Medicine articles is that both observational studies and randomized controlled trails have weaknesses. Epidemiology doesn’t do a good job of identifying how effective a treatment may be, which is why the researchers were a bit nonplussed when their expensive trials of statins for severe respiratory problems struck out. RCTs are not always well designed to detect side effects.
Tell your statin story below. Anecdotes are the least accurate scientific evidence, but they are not meaningless. If you have great success with statins, share your experience. If you have had trouble with side effects, please let us know too.