Pros and Cons of Statin Therapy

Here are two scientific papers, published only one month apart, showing the opposite sides of the contentious statin debate.

Many medical issues are like this, where there is no universally “right” or “wrong” approach. Instead, medical care must be customized for the complicated variations between individuals and even for different times in their lives.

Benefits of statins repeatedly underestimated and the harms exaggerated | London School of Hygiene & Tropical Medicine | LSHTM – 09 September 2016

Common painkillers such as ibuprofen and diclofenac that are used by millions of people in the UK have been linked to an increased risk of heart failure, according to new research published in the British Medical Journal.  

Doctors, patients and the public now have more help to make informed decisions about statin therapy, thanks to a major review of the available evidence on the safety and efficacy of the drug published in the Lancet.  

The authors, including researchers from the London School of Hygiene & Tropical Medicine, warn that the benefits of statin therapy have been underestimated, and the harms exaggerated, because of a failure to acknowledge properly both the wealth of evidence from randomised trials and the limitations of other types of studies.

“The best available scientific evidence tells us that statins are effective, safe drugs that have a crucial role in helping prevent cardiovascular disease: the leading cause of morbidity and mortality worldwide.”

Our review shows that the numbers of people who avoid heart attacks and strokes by taking statin therapy are very much larger than the numbers who have side-effects with it.

In addition, whereas most of the side-effects can be reversed with no residual effects by stopping the statin, the effects of a heart attack or stroke not being prevented are irreversible and can be devastating.

“Consequently there is a serious cost to public health from making misleading claims about high side-effect rates that inappropriately dissuade people from taking statin therapy despite the proven benefits.”

Interpretation of the evidence for the efficacy and safety of statin therapy. The Lancet: DOI 10.1016/S0140-6736(16)31357-5  

Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak | Cardiology | JAMA Internal Medicine | The JAMA Network | Rita F. Redberg, MD, MSc; Mitchell H. Katz, MD – JAMA Intern Med. Published online November 13, 2016.

The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease (CVD) events.

Although the task force did their usual careful job of reviewing the evidence, the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation.

The task force evidence report estimated an absolute benefit for use of statins of 0.40% for all-cause mortality and 0.43% for cardiovascular mortality and indicated that the absolute benefit was greater for patients at greater baseline risk.

Notably, the evidence report did not exclude studies that included patients taking statins for secondary prevention, who have a higher baseline risk of cardiac events and death and thus are more likely to benefit from therapy that inflates the benefit attributed to a primary prevention population.

In contrast, a meta-analysis of 11 studies and 65 229 patients receiving statins for primary prevention, in which patients receiving statins for secondary prevention were excluded, found no benefit of statins for reducing all-cause mortality.

Exacerbating the potential bias, all of the trials included in the task force evidence report2 were industry-sponsored except 1, trial,5 and that trial contributed 0.2% of the weight to the mortality calculation.

Industry-sponsored studies have been shown to report greater benefit and lesser adverse effects than noncommercially sponsored trials of the same drugs. Whether this is true for statins and primary prevention of CVD is unknown.

Understanding the evidence base in evaluating harms of statin therapy is also critically important. Although the benefits of any preventive therapy accrue according to risk of disease (greater benefit in higher-risk patients), the harms of therapy usually distribute equally over all risk levels. Thus, persons at low risk have little chance of benefit but equal chance of harms and thus are more likely to have a net harm.

Many of the trials did not ask about commonly reported statin effects, such as muscle pains and weakness, and only recorded myopathy, for which an increase in creatine kinase levels was required. Because most muscle problems do not involve an increase in creatine kinase levels, this leads to a significant underestimate of muscle problems.

Other studies have estimated that closer to 20% of statin users have muscle problems.

Additionally, the actual trial data are largely held by the Cholesterol Treatment Trialists’ Collaboration on behalf of the industry sponsor and have not been made available to other researchers, despite multiple requests over many years.

Although reported rates of adverse events in clinical trials are low, this does not reflect the experience of clinicians who see patients who are taking statins.

Even though the evidence may be insufficient to support statin treatment for asymptomatic patients, these new guidelines may have a beneficial effect.

Many patients are treated with statins, even though their risk of a cardiovascular event in the next 10 years is less than 7.5%;

If physicians follow the task force recommendation and do not recommend treatment for primary prevention unless risk is greater than 10% in the presence of a risk factor, many patients would potentially avoid unnecessary treatment.

There are unintended consequences of the widespread statin use in healthy persons.

For example, people taking statins are more likely to become obese and more sedentary over time than nonstatin users, likely because these people mistakenly think they do not need to eat a healthy diet and exercise as they can just take a pill to give them the same benefit

Although the estimates of the benefits of statins for primary prevention used by the task force may be inflated, even if these estimates are accurate, this is still a relatively weak intervention. The task force evidence report estimated that to prevent one death from any cause over a 5-year period, 244 patients would need to take a statin daily.

Certainly, one reason the debate is intense is because of the large market for statins if these drugs are recommended for primary prevention. The global market for statins has been estimated to be a staggering $20 billion annually in the last decade.18,19 For that kind of investment, better data on risks and benefits should be required.

In deciding on any therapy, it is important to understand the risks and benefits, particularly for healthy people.

It is incumbent on clinicians to be sure that before recommending that a patient take a daily pill that has multiple adverse effects, there is evidence that the medication will lead to a better quality of life, longer life, or both. Such evidence is lacking for statins in primary prevention

Given the serious concerns about the harms of the reliance on statins for primary prevention, it is in the interest of public health and the medical community to refocus efforts on promoting a heart-healthy diet, regular physical activity, and not smoking.  

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