Risk for muscle symptoms from statins small, far outweighed by CV benefits
Click Here to Manage Email Alerts
While statin therapy may cause a small excess of mostly mild muscle pain, most muscle symptoms reported in statin trials were not caused by the drug, according to a meta-analysis presented at the European Society of Cardiology Congress.
The Cholesterol Treatment Trialists’ Collaboration concluded that the risks for muscle symptoms from statins are much lower than the drugs’ known CV benefits.
“Statins can cause serious muscle problems, but this is rare,” Colin Baigent, FMedSci, professor of epidemiology at the Nuffield department of population health at Oxford University and director of the Medical Research Council Population Health Research Unit, said at a press conference. “We are talking about myopathy, where muscles can become damaged and creatine kinase rises. The effects of statins on other muscle symptoms without biochemical evidence of damage are less certain. There has been quite a bit of information on social media and in the press about statins and their effect on muscle symptoms, with many nonrandomized studies claiming that the risk of muscle symptoms with statins is extremely high. In response to this, we put together a program of data collection, validation and analysis to try and provide reliable information, since the nonrandomized studies suffered from biases.”
The researchers conducted an individual participant data meta-analysis of 123,940 participants (mean age, 63 years; 28% women; 48% with previous vascular disease; 18.5% with diabetes) from 19 trials of statins vs. placebo. The findings were simultaneously published in The Lancet.
Over a weighted average median of 4.3 years, individuals assigned statins were slightly more likely to report muscle pain or weakness than those assigned placebo (27.1% vs. 26.6%; RR = 1.03; 95% CI, 1.01-1.06), according to the researchers.
At 1 year, statin therapy was associated with a 7% relative increase in muscle pain or weakness (RR = 1.07; 95% CI, 1.04-1.1), which corresponded to an absolute excess rate of 11 events (95% CI, 6-16) per 1,000 person-years, indicating that one in 15 reports of muscle pain or weakness were actually due to the statin, Baigent and colleagues found.
‘It is due to something else’
“This means that for the vast majority of people who experience muscle pain or weakness on a statin soon after they started, it is not due to the statin,” Baigent said at the press conference. “It is due to something else — aging, thyroid disease, exercise. Something else is causing it.”
After 1 year, there was no excess of muscle pain or weakness reports from individuals assigned statins compared with those assigned placebo (RR = 0.99; 95% CI, 0.96-1.02).
By contrast, Baigent said, statins prevent 25 CV events per 1,000 for 5 years of treatment in the general population and 50 CV events per 1,000 for 5 years of treatment in the secondary prevention population.
Compared with placebo, both more-intensive statin regimens (RR = 1.08; 95% CI, 1.04-1.13) and less-intensive statin regimens (RR = 1.03; 95% CI, 1-1.05) were associated with more muscle pain or weakness reports during the course of the study, and there was a small excess of reports for more-intensive statin regimens after the first year (RR = 1.05; 95% CI, 0.99-1.12), according to the researchers.
“What this now means is that we need to do two things,” Baigent said. “First of all, we need to find ways of better managing muscle pain in patients taking a statin, because when they stop taking a statin, most of the time they are doing it when the drug isn’t actually the cause. The second thing we need to do is provide better information in package inserts about the real risks of pain when taking a statin. That is a very important objective that we now have. Statins are one of the most effective medicines we have in our armamentarium, and they are responsible for reducing the risk for coronary heart disease, but their value is being limited by people stopping statins or not being willing to start them if they are at high risk of muscle pain.”
The researchers also conducted a meta-analysis of four trials of more-intensive statin regimens compared with less-intensive statin regimens, and the results were similar to the statin vs. placebo analysis.
The RR did not vary by statin or by clinical circumstances, the researchers found.
“There’s no one statin that’s causing the problem, which is reassuring,” Baigent said.
Focus on CVD risk
In a related editorial published in The Lancet, Maciej Banach, MD, PhD, FNLA, FAHA, FESC, president of Polish Mother's Memorial Hospital in Lodz, Poland, research institute head of the Cardiovascular Research Centre, University of Zielona Góra, Zielona Góra, Poland, and professor of cardiology and head of the department of hypertension at Medical University of Lodz, wrote that “it should be strongly emphasized that the small risk of muscle symptoms is insignificant in comparison with the highly proven cardiovascular benefits of statins. Thus, the possible side effects of statins should not be considered before treatment is initiated; instead, focusing on how best to reduce cardiovascular disease risk in these patients should be considered first, and optimal treatment should be initiated accordingly, because ultimately (if statin intolerance recommendations are strictly followed), statin treatment can be continued in up to 98% of patients.”
References:
- Banach M. Lancet. 2022;doi:10.1016/S0140-6736(22)01643-9.
- Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;doi:10.1016/S0140-6736(22)01545-8.
Perspective
Back to Top
Gregg C. Fonarow, MD, FACC, FAHA, FHFSA
Statin therapy has been demonstrated to be highly effective in preventing and treating atherosclerotic CVD with reductions in acute coronary events, stroke, the need for hospitalization and premature CV death.
Despite these proven benefits, concerns regarding potential side effects, particularly skeletal muscle pain and weakness, have resulted in eligible patients not initiating or continuing on statin therapy.
In individual clinical trials where patients are randomly assigned to either statin medication or matching placebo in a double-blind fashion, the rates of muscle pain and weakness with statin therapy is generally low and comparable to placebo. In clinical practice, where patients know they are receiving statin therapy, high rates of muscle pain and weakness are reported.
In this new, very large analysis of 23 trials of statin therapy involving over 150,000 men and women, there was very little excess in muscle pain, and when it occurred, more than 90% of the time it was not due to statin therapy. The small excess in muscle pain detected was usually mild and did not differ by which statin or which dose.
The key findings are that the benefits of statins outweigh the potential risks and that for most patients experiencing muscle pain or weakness they perceive to be caused by the statin, those symptoms are not actually due to the statin.
These findings should be very reassuring to patients concerned with or experiencing skeletal muscle related symptoms, as the probability that the symptoms are actually caused by the statin is low and less than 1 in 10.
Collapse
Baigent C, et al. Hot Line 9. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
Read more about
Click Here to Manage Email Alerts