Review Touts Benefits of Statins, Seeks to Dispel Safety Concerns


A new review aims to clarify the evidence regarding the safety and efficacy of statins, concluding that the benefits of the drugs in terms of reducing major vascular events far outweigh any proven or potential risks.

There are public health consequences from making misleading claims about the safety and efficacy of statin therapy and the rationale for performing the review was to clear up some of the confusion about how to interpret different types of evidence and help people make more informed decisions, lead author Rory Collins (University of Oxford, England), told TCTMD.

“There was almost a bizarre approach by some people to dismiss the randomized controlled evidence and to argue that the observational evidence was reliable,” he said.

Having misinformation in the public domain is a problem, Collins et al say, because it can have a negative impact on patient behavior. They point to research showing that negative media coverage of statins is linked to reduced compliance among patients taking the drugs.

“In such circumstances, much greater caution is warranted than has sometimes been the case when making claims about possible side effects, since otherwise patients at high risk of heart attacks, strokes, and related deaths, and their doctors, may well be inappropriately dissuaded from using statin therapy despite the proven benefits,” Collins et al write.

In the review, the authors consider the relative strengths and limitations of randomized trials and observational studies, evaluate the evidence on the safety and efficacy of statins, and discuss the public health implications of misinterpreting data regarding the effects of the drugs.

“It’s about time,” Howard Weintraub, MD (NYU Langone Medical Center, New York, NY), commented to TCTMD. “This was long overdue.”

Weintraub said there is a disconnect between perceptions about statins among patients and what has been proven in clinical trials, describing how some of his patients attribute any aches and pains to the drugs because of what they’ve seen in news reports or uncovered in online searches.

“This is something that I think is understandable but regrettable,” he said.

Noting the 309 references cited in the review, Weintraub said the authors do a “very good job” describing the safety and efficacy of statins.

“They really went out of their way to show how certain inferences may have been made in error based upon statistical sampling and they go out of their way to show how the benefits of these medications strongly outweigh the problems that have been cited as being caused by the drugs,” Weintraub said.

The review was published online September 8, 2016, ahead of print in the Lancet.

Look To the Randomized Evidence

The review leads off with a discussion about the merits of randomized and observational evidence, and the authors say that even though observational studies can detect rare outcomes and assess the effects of longer durations of exposure, the type of information provided is limited when there is extensive randomized evidence available.

Not only have the limitations of observational studies often been underestimated when attributing adverse effects to treatment (such as misleading claims that statins cause side effects in one-fifth of patients), but also the strengths of randomized trials with masked treatment allocation and systematic ascertainment of many different types of adverse event have been underestimated for the reliable assessment of the safety and efficacy of treatment,” they write.

Focusing on the randomized evidence, they say, shows that statin therapy reduces the risk of major vascular events with only a small increase in adverse effects. They calculate that using statins to reduce LDL cholesterol by 2 mmol/L (77 mg/dL) for 5 years in 10,000 patients would prevent major vascular events in 1,000 patients with pre-existing vascular disease and 500 patients who are at increased risk.

As for adverse effects, Collins et al say the only ones that have been reliably connected to statins are myopathy and diabetes, with a probable increase in hemorrhagic stroke. Nevertheless, the absolute risks remain small, they say, calculating that over a 5-year span in 10,000 patients, statin therapy would cause five cases of myopathy, 50 to 100 new cases of diabetes, and five to 10 hemorrhagic strokes.

“The large-scale evidence available from randomized trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms,” the authors write.

“It is, therefore, of concern that exaggerated claims about side effect rates with statin therapy may be responsible for its underuse among individuals at increased risk of cardiovascular events,” they continue. “For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.”

As a further response to claims of side effects of statin therapy, the Cholesterol Treatment Trialists’ Collaboration, of which several of the review authors are part, has announced plans to launch a new meta-analysis to assess the relative and absolute risks of adverse events tied to lipid-lowering therapy, with preliminary results expected to start being released early next year.

The Lancet Weighs In

In an accompanying note, Lancet Editor-in-Chief Richard Horton draws a parallel between fears of statin side effects and fears of adverse effects of the MMR vaccine bred by a study that has since been retracted to explain the decision to publish and promote this review (the journal also held a press conference).

“One lesson of MMR was that, in the face of an unjustified claim that could harm public health, the scientific community, including journals, should respond quickly and robustly to counter that claim,” he writes. Here, the Lancet is aiming to do just that.

In an email to TCTMD, David Maron, MD (Stanford University School of Medicine, CA), supported the journal’s stance.

“When the evidence is so clear, and patients are harmed by the false impression that a therapy that can help them is dangerous, I commend a journal for taking a stand and forcefully stating its opinion,” he said.

“This review is important to help set the record straight,” Maron said. “As a cardiologist, it is very frustrating to see patients who don’t receive therapy that can save lives and prevent heart attacks and strokes because of misunderstanding the facts.”

He added that he hopes and believes that publication of the review will lead to an uptick in appropriate use of statins, noting, however, that it is written in a form that most patients would not be able to read or understand.

Weintraub had a similar critique, and was more skeptical about the potential impact of the review in terms of reversing some of the negative perceptions about statins. I would really love it if it did. But having said that, I’m not sure that it will.”

For his part, Collins said he was unsure what effect publication of the review would have, but he said it will not quell the criticisms of the “anti-statin fanatics.”

“But I hope for those who are more agnostic, that by presenting both the rationale for relying on particular types of data and then what those data show will be helpful for that audience,” he said. “But it’s certainly not going to convince the people who believe statins are evil or believe it’s a big pharma conspiracy.”

 

Sources
  • Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;Epub ahead of print.

  • Horton R. Offline: lessons from the controversy over statins. Lancet. 2016;Epub ahead of print.

Disclosures
  • Collins reports working for the Clinical Trial Service Unit & Epidemiological Studies Unit at the University of Oxford, which has received research grants from Abbott, AstraZeneca, Bayer, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Schering, and Solvay; and being the co-inventor of a genetic test for statin-related myopathy risk.
  • Maron and Weintraub report no relevant conflicts of interest.

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