A Swedish warning on the potential risks of using statins in high doses has triggered strong criticism from some of the top U.S. cardiologists.
The timing of the debate is apt: Recently revised recommendations in the United States call for lowering cholesterol more than ever before as a way of reducing the risk of heart disease, and that translates into more people taking statins, and in higher doses.
That trend is troubling, claims a report in the June 3 issue of the British Medical Journal, because the side effects of taking these cholesterol-lowering medications in higher doses could be potentially dangerous.
However, U.S. experts said this is not the case and that the authors of this article ignored the findings of many large clinical trials that show the benefits and safety of statins, even in large doses.
The American National Cholesterol Education Program said last year that people at high risk of heart disease should be treated more aggressively. Aggressively lowering cholesterol means that LDL cholesterol should be lowered to less than 1.81 millimoles per liter of blood (mmol/l) in high-risk individuals. Current guidelines generally recommend 2.56 mmol/l.
According to Uffe Ravnskov, an independent researcher from Lund, Sweden, achieving this new goal would mean that most of the western world's adult population would be on statins, and doses would have to be more than eight times higher than currently used.
Doses this high would increase both the number and seriousness of side effects, Ravnskov's team contended. Side effects could include heart failure, myalgia and rhabdomyolysis (which destroys muscle tissue), neurological problems and cancers.
In addition, the researchers claimed that clinical trials suggest that higher doses of statins do not lower overall mortality, and side effects are generally under-reported.
"In the paper we have argued in detail why we distrust the reporting of side effects in the statin trials. There are many indications that they are under-reported. It is a question of confidence," Ravnskov said.
And any reduction in nonfatal events from the use of high doses of statins may be outweighed by more numerous and more severe side effects, Ravnskov's group concluded.
However, one expert thinks Ravnskov's group is entirely wrong.
"Ravnskov's arguments are not compelling," said Dr. Steven E. Nissen, interim chairman of the department of cardiovascular medicine at the Cleveland Clinic, and president of the American College of Cardiology. "High doses [of statins] are safe."
Nissen noted that many studies have shown these drugs are safe. "There are side effects," he said. "But most people tolerate these drugs very well. There is no data on heart failure, there is no good data on neurological symptoms, and there is certainly no compelling data on cancer."
Nissen believes that the benefits of these drugs outweigh the risks. "Ravnskov is understating the benefits, which have been shown in dozens of clinical trails across large populations," he said.
Statins are not for everyone, Nissen noted. In terms of how low cholesterol should be, Nissen said it depends on who you are. "If you have existing coronary disease, probably as low as possible," he said.
"When you examine Ravnskov's arguments, which have been around for longer than I have, they just don't cut it," Nissen said.
Another U.S. expert agreed with Nissen.
"The authors in this article are stating that occasional side effects that are entirely reversible should be given greater consideration in therapeutic decision-making than significant reductions in the risk of myocardial infarction and stroke," said Dr. Gregg C. Fonarow, a professor of cardiology at the University of California, Los Angeles.
"There are countless well-controlled trials demonstrating [that] the benefits of statin therapy greatly outweigh the potential risks, even at high doses," he said.
The study authors overlooked data from multiple randomized clinical trials that disprove their statements, Fonarow added. "They selectively cite studies only if it supports their viewpoint, even if the totality of evidence negates their view."
"For example, they state that statins may cause heart failure, but seem to be unaware of the studies showing that statins lower the risk of heart failure compared to placebo," Fonarow said.
"The views expressed in this article are not consistent with other very careful and scientifically rigorous analyses on this subject," Fonarow said. "Nor are they consistent with peer-reviewed statements from the American Heart Association, American College of Cardiology, nor the National Heart, Lung, and Blood Institute."
However, one of the authors of the article disagreed with the idea that statins carry no dangers. "If you look at the data, that's not really true," said Dr. Morley C. Sutter, an emeritus professor of pharmacology at the University of British Columbia.
"They upset the liver, they upset muscle function, and it is possible that they alter brain function," he said. "The fact that they have as little undesirable effects as they do is quite miraculous."
The reason this information isn't taken into account is due to the large commercial interest in statins, Sutter claimed. "It's the biggest-selling drug in the world -- billions of dollars," he said.
As far as taking a statin to prevent a heart attack, Sutter said he's against it. "Certainly, unless I had a heart attack, I would not take a statin," he said. "If I were a woman, I would not take a statin because there is no evidence that they help women."