Statins in the real world

By Alan Cassels, June 2014

The large drop-out rate during clinical tests on statins has disguised the dangers inherent in their use.

In early April this year, 68-year-old Sooke resident Veronica Diment finally got an explanation of her health problems and an official diagnosis: polymyositis, a chronic inflammation of many muscles.

The former language teacher, who now runs a rural vacation retreat near Sooke, told me the diagnosis landed like a bomb in her life. What was so startling was not that she finally had a name for the disabling condition which has left her at times without the muscle strength to climb the stairs, it was how matter-of-factly a specialist described the source of this auto-immune disorder: “long-term statin use.”

Many pharmaceuticals can improve the quality and length of our lives, yet as Diment’s experience with statins demonstrates, they can also do the opposite. 

Statins are drugs that lower cholesterol, and the most popular ones, such as Crestor (rosuvastatin), Lipitor (atorvastatin) or Zocor (simvastatin) are among the most widely prescribed drugs in the world. In the US, a quarter of the adult population over 45 takes a daily statin. Here in BC close to half a million people take statins in the hopes it will prevent a heart attack or stroke. 

We have known for at least a decade that statins are not for everyone. Large meta-analyses of the drug-industry-funded trials show surprisingly small benefit, while the drugs are made to appear perfectly safe. Men with established heart disease might have a somewhat lower risk of death with statins; however, women, the elderly, and ordinary people at low risk of heart disease do not live any longer with statin therapy. The drugs’ popularity seems to defy such realities.

Veronica Diment talks with energy and dynamism; she’s the sparkly kind of person who seems enthusiastic about everything. She says that when she was in her 50s she was very healthy and active—she rode her bike, swam, and walked. She felt lucky to be someone who rarely went to doctors and who didn’t take any prescription drugs. After surgery on her spine 15 years ago, however, she faced a long road to recovery, during which time she was diagnosed with type 2 diabetes. “Runs in the family,” her doctor explained. In 2010 he convinced her to take a low dose of Lipitor to reduce her cholesterol levels. (Diabetes 2 meant that her chances of having a stroke or heart attack were doubled.) 

“I questioned the idea a bit but then went along with his suggestion,” she said, adding “at no time did he warn me of the potential risks. He just said that this drug was in widespread use and was a valuable preventative.”

For some people the side effects of statins, most commonly the muscle weakening and general tiredness, start right away. In the big clinical studies of statins at least a third of the people taking the drugs dropped out of the trial even before it got going, during the aptly-named “washout period.” For example in the large British Heart Protection Study, after 10 weeks on 40 mg of simvastatin, 11,609 patients dropped out. Many of those “excluded” patients were kicked out of the study because either the drug didn’t work for them, they had increased liver enzymes, or increase in CK, or other reasons. Suffice to say the drop-out rate is high, and as high as 78 percent in one very large statin trial. 

The people left in these studies aren’t like average people.The wash-out period sleight-of-hand is a crucial piece of information that physicians don’t always learn from the published scientific literature or by attending drug company-sponsored scientific meetings. The result? Doctors and patients believe that the drugs are much more well-tolerated than they actually are.

Diment continued taking her statin for a year and a half, when she began to feel exhausted and weak. She asked at a pharmacy if her muscle aches were due to the Lipitor, but the youngish pharmacist said they couldn’t be due to the drug as “too much time had passed.” After several falls, her doctor sent her for a CT scan which turned up nothing. Then, as if a light came on, he said: “Oh, you’re on a statin. I need to send you for a CK count.”

CK stands for Creatine Kinase, an enzyme expressed by a variety of tissues and cells. A high CK blood reading can be a marker of a heart attack, kidney failure, or rhabdomyolysis, which is severe muscle breakdown. Diment’s CK test results came back at 19,400 (normal is 200-400) and her doctor said: “I’ve never seen a count this high.” She stopped the drug immediately yet her weakness persisted and worsened. “I was unable to walk or lift my arms. I became ever weaker and spent the first three months of 2012 bedridden due to paralysis of my legs and arms.” Over the next year, she regained her ability to walk with the aid of a leg splint and a cane but in August 2013, the weakness worsened in her hands, arms, trunk and legs. Diment says she now uses a walker “because I am always in danger of falling.”  

After many tests and more inconclusive results, she was eventually referred to the Neuro-Muscular clinic at Vancouver General Hospital where a specialist diagnosed it right away: polymyositis, adding that it was definitely caused by the statins.  

At least she now had an answer, but what an ordeal it’s been.

 

Perhaps because I have researched statins for over a decade nothing in Diment’s story surprised me. What has always been a mystery has been the difference in rates of adverse effects such as memory, muscle and balance problems in “real world” statin takers compared to people in clinical studies. It has become clear to me that while the companies have been manipulating the clinical studies to make the muscle-weakening and other adverse effects disappear, it’s harder to fool people in the real world.

One person who knows this intimately is Dr Beatrice Golomb, who has been researching and publishing the real world effects of statins for more than 15 years at the University of California at San Diego. She has carried out some of the world’s most comprehensive examinations of statin harm, (www.statineffects.com/info) with a focus on collecting actual reports from real people in the real world (a far cry from the rarefied world of a drug company-controlled clinical trial). Golomb recently lambasted a group of researchers for downplaying the dangers of statins, saying that when physicians misunderstand the evidence of harm of statins “many patients remain on the drugs and die.” As if to underline how profound the ignorance is she says: “those deaths would not even be recognized as statin-related.”

Others here in BC have studied company-sponsored trials of cholesterol-lowering drugs and even those show a marginal, some might say non-existent benefit of statins for most people. UBC’s Therapeutics Initiative (TI), which is funded by the BC Ministry of Health and takes no money from the pharmaceutical industry, has published several newsletters about statins. A 2003 letter sent out to all of BC’s 4000 or so general practitioners noted that “no study has shown a significant reduction in mortality in women treated with statins” (www.ti.ubc.ca/letter48). In other words: Why would physicians even prescribe these drugs to women?

Its latest newsletter, published in May, does a thorough examination of the harms related to statins. I asked Dr Jim Wright, the director of the Therapeutics Initiative, if polymyositis is common in women who take statins and he said it’s not, but it is “the kind of thing you’d see in case reports.” His newsletter documents the other kinds of rare but serious effects found in case reports on statin users, including “peripheral neuropathy, sexual dysfunction, gynecomastia (breast enlargement), irritability, aggression, behaviour change, memory loss, depression, psychosis, interstitial lung disease, heart failure, weight gain, Parkinson syndrome, lupus-like syndrome, dermatomyositis, other auto-immune syndromes, pancreatitis and others.” (See www.ti.ubc.ca )

The most common adverse effect, however, remains the muscle pain, aches, soreness, weakness or fatigue that happens to between one in 20 and one in 4 statin patients in the real world. Even when patients have normal CK readings they can be experiencing muscle damage, and worst of all, some patients—like Diment—can experience muscle destruction and not know it.

Adding to the chorus of warnings around statins, last year pharmaco-epidemiologist Colin Dormuth, also with TI but based here in Victoria, published findings that said people taking higher strength statins faced an increased risk of kidney injury. Part of Canada’s Drug Safety and Effectiveness Network (DSEN), his group is part of a Canada-wide effort to study the real world effects of drugs. By tapping into large, comprehensive health databases—such as BC’s PharmaNet—Dormuth and his colleagues have also found that higher dose statins turn more people into diabetics than lower dose ones, findings that have just been published. 

With wider awareness of the work by the TI, DSEN, and researchers like Beatrice Golomb, the world is starting to seriously question these drugs. A May article in the New York Times (“A New Woman’s Issue: Statins”) says that even though many otherwise healthy women take statins, “some research indicates the drugs will do them little good and may be more likely to cause serious side effects in women.”

One of the biggest problems with statins is that even if a person is not debilitated, the drugs can interfere with the one thing a person needs to do to maintain cardiovascular health: exercise.

Over the last two decades I’ve seen the aggressive marketing of and overenthusiastic embrace of statins arriving with the message that the drugs are perfectly safe. That picture is thankfully changing.

I asked Veronica Diment to describe her experience to me in an email: “I feel a hot brew of grim, grim anger, disappointment in my lack of critical thinking when I decided to accept the doctor’s idea that I needed to go on the drug.” Feeling like she’d been deceived by the medical system and betrayed by big pharma, she says “worst of all is the feeling of having been robbed of an active old age,” she writes, adding, “I feel as if I have been fast forwarded into my late 80s.”

She said she wanted to tell her story because “I don’t want anyone to go through the experience I have had,” adding that if you’re told to take statins as a preventive measure, “make sure you are aware of the potential of severe side effects.”

Alan Cassels is a Victoria pharmaceutical policy researcher and author of three books, all which contain chapters on statins. You can read his other writings at www.alancassels.com or follow him on twitter @akecassels.