DID YOU KNOW...
individuals stop taking statins due to negative publicity!

Prepared by John. A. Sawdon M.Sc. Public Education & Special Projects Director,
Cardiac Health Foundation of Canada

Background

Although the first commercially approved statin in North America to control cholesterol was approved in 1987 by the United States of America Food and Drug Authority (FDA), research and interest on the casual connection of blood cholesterol, atherosclerosis and coronary heart disease has been underway for almost a century.1 The link between cholesterol and atherosclerosis goes back to 1910 when it was discovered that atherosclerotic plaques from human aorta’s had more than 20 times the level of cholesterol than did normal aorta’s.

In 1939 Norwegian Carl Muller discovered several large families in which high blood cholesterol levels and premature heart attacks together were an inherited trait. This finding was the first genetic connection between cholesterol and heart attacks. In the mid 60’s the genetic understanding of this syndrome known as Familial Hypercholesterolemia from inbred families identified two distinct forms of FH. The first with two cells one from each parent called homozygous form FH which found severe hypercholesterolemia at birth (up to 800 mg/dl) and heart attacks occurring as early as age 5. The second called heterozygous form FH in which one gene was passed on from one parent only found blood cholesterol levels from 300mg/dl to 400mg/dl . Heart attacks for this latter group typically occurred between 35 and 60 years of age. These findings supplemented with animal studies suggested a causal link between cholesterol and atherosclerosis and coronary heart disease. In the 1950’s John Gofman University of California found that heart attacks correlated with elevated levels of blood cholesterol and that cholesterol was contained within low density lipoprotein (LDL-C). He also observed that heart attacks were less frequent when blood contained elevated levels of high density lipoprotein (HDL).

The Framingham Heart Study found evidence that individuals with higher blood cholesterol levels were more likely to experience heart attacks in subsequent follow up years.

As evidence grew that high blood cholesterol levels were linked to heart disease, scientists, universities and industry began to search for drugs that would lower blood cholesterol. In 1971 Citrinin was discovered which inhibited HMGCoA reductase and lowered serum cholesterol in rats. This drug however proved toxic to kidneys and research was suspended. This led to the creation of Compactin by Akira Endo with Sankyo of Tokyo. In collaboration with Akira Yamamoto Osaka University Hospital a series of clinical trials with patients with severe hypercholesterolemia was undertaken leading to a 30 percent reduction of cholesterol without side effects. This first statin however was discontinued due to clinical trials using high dosages with dogs which led to lymphoma. It was revealed that dogs were receiving 200 times the dosage that humans were given. These trials then led to pravastatin with a maximum dosage of 25 miligrams. During the early 80’s Merck who had liaised with Sankyo created and tested Lovastatin the first approved statin in the United States. Since this time 6 statins have been introduced to the market place with Pfizers Lipitor (atorvastatin) being the most popular.2 In 1997 Bayer Pharmaceuticals introduced cerivastatin ( Baycol) and began a number of clinical trials. Although dosage for this potent drug was recommended by Bayer’s scientists to not exceed .4 milligrams, Bayer applied for and received approval for .8 milligram dosage. This led to a number of cases of rhapdomyolysis resulting in 18 deaths worldwide with 12 deaths occurring in the United States. Bayer subsequently pulled this drug from the market place in 2001. 3

In 2010 it was estimated that 30 million people worldwide were taking statins. Since 2016 due to patent expirations 4 several statins have become available as less expensive generics.

Since this time considerable debate has occurred that was fueled by clinical studies as to whether statins prevent heart disease and whether these same statins actually do harm. Some studies have suggested that statins cause muscle deterioration, contribute to cognitive decline and increase the risk of diabetes. These findings fuelled by the discussion that cholesterol is normal and is required by the body to grow healthy cells has led to questioning “why should I take statins at all”?

In a meta-analysis study undertaken in 1995 it was discovered that 65% of patients continued with statin therapy.4 This same article indicated that a Finnish study found a 10 year compliance rate of 44% for statin therapy. People over 74 years of age and under 45 years had the lowest rates of compliance.

In a 2010 comprehensive meta-analysis including the Cochrane Database of Systematic Reviews adherence to statins was found to be problematic with rates fluctuating broadly based on gender, ethnicity and race 5. One year mortality rates for black patients with acute myocardial infarction (heart attack or MI) are 12% to 35% higher than for white patients. In hospital mortality is 30% higher for women than men before the age of 35. In terms of statin use and adherence rates, black patients on medicare have 67% higher odds of discontinuing statin therapy compared to patients of white race. In this same study women were found to have a 10% lower adherence rate to statin therapy than men. In a study of 10,000 US patients on statin use called Understanding Statin Use in America and gaps in Education (USAGE) it was found that 70% had continued their statin therapy. Of those who stopped their statin therapy 32% indicated it was due to cost while 62% indicated it was because of side effects.

In continuing the discussion of why patients stop taking statins especially those high risk individuals with previous histories of cardiovascular disease, we need to pay attention to side effects including potential for diabetes. Researchers for the Canadian Network for Observational Drug Effect Studies6 conducted a study by analyzing the records of 136,966 patients over the age of 40 in Canada, the United States and United Kingdom. 66% of patients were prescribed high potency statins after suffering a major cardiac event. High dosage included more than 10 mg rosuvastatin (Crestor), 20 mg of atorvastatin (Lipitor), or 40 mg of simvastatin (Zocor). The study found that when comparing those taking high dosage statins to low dose statins, those taking high dosage statins had a 15% relative increase in risk of diabetes over two years. This finding creates a dilemma for Doctors and patients alike. It has been a given that those who have had a major cardiac event should be prescribed statins to reduce the potential of having another heart attack or stroke. In light of these findings and the increase in negative news stories around statins including potential side effects, the question becomes ‘To statin or not to Statin”.

A study by Sune Fallgaard Nielson and Borge Gronne Nordestgaard which tested the effect of negative news stories on statin adherence rates in Denmark may help to answer this question7. This study examined 674,900 patient records of individuals over age 40 that were prescribed statins between 1995 and 2010 and then were followed until December 31, 2011. It also identified all news stories about statins (1931) during this time period and classified these as follows: 110 graded as negative, 1090 graded as neutral and 731 graded as positive. They analysed this and found that early discontinuation of statins increased with negative statin related news stories, statin dose, being male, and living in cities with ethnicity other than Danish. They also found that early discontinuation of statin use was also associated with increased risk for myocardial infarction (25%) and death from cardiovascular disease (18%). In a 2012 published report in the Journal of Arthritis Care & Research, Mary De Vera Ph.D. with University of British Columbia School of Population & Public Health and Arthritis Research Centre of Canada found that Rheumatoid Arthritis patients who discontinue statin therapy are at increased risk of death from cardiovascular disease. This study found that statin discontinuation was associated with a 60% increased risk for cardiovascular disease deaths and 79% for deaths from all causes.8 Barbara H. Roberts M.D., Director of Women’s Cardiac Centre, Miriam Hospital, Rhode Island and Associate Clinical Professor of Medicine, Alpert Medical School of Brown University and ranked as one of the Top Doctors for Women by Women`s Health Magazine is clear that statins should never be prescribed for healthy women. She indicates in her book, “The Truth about Statins” that statins have never been of benefit to women to just lower cholesterol. She also indicates that statins have greater negative side effects for women than men. In 2012 the US FDA called for safety warnings on statins, saying the drugs posed an elevated risk of inducing memory loss and raising blood sugar levels. In early 2013 Health Canada called on statin makers to update labels to include warnings about the increased risk of diabetes from statins and urged Doctors to monitor patients taking statins who were at risk of diabetes.

Although we have not definitively answered the question “To Statin or Not to Statin”, we encourage you to have a discussion with your Doctor about any concerns you have. Dr. Barbara Roberts poses a series of questions in her book “The Truth about Statins” that women should ask Doctors in exploring whether to take statins or not. These questions centre on risk, using diets as a way to lower cholesterol and exploring potential side effects of statins. The research is clear that statins reduce hospitalizations, myocardial infarction and death for those who have had a major cardiovascular event previously. For those looking to prevent cardiovascular disease including atherosclerosis in the first place the science is not so clear. We encourage you to conduct your own research and to engage in a discussion with your Doctor.

This article is intended to provide you with information from which to make decisions and to protect your health in managing and or preventing cardiovascular disease. We encourage you to let us know if this article was helpful for you including suggestions or questions you hope get answered through future articles.

Please send your comments and reactions to jsawdon@cardiachealth.ca

References:

  1. Endo Akira, Beppu Teruhiko: A historical perspective on the discovery of statins. Proceedings of the Japan Academy series B Physical and Biological Sciences 2010 May 11; 86(5):484-493 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108295/
  2. Statin from Wikipedia, the free encyclopedia. http://en.wikepedia.org/wiki/statin
  3. Roberts, Barbara H M.D. The Truth about Statins: Risks and Alternatives to Cholesterol Lowering Drugs; Pocket Books 2012, a Division of Simon & Shuster 1230 Avenue of the Americas, New York 10020 ISBN 978-1-4516-5639-8
  4. Adherence- Keeping up the Statin Usage Through the Years; http//www.statinanswers.com/compliance.htm
  5. Lewey Jennifer M.D., Shrank William H.MD. MSHS, Bowry Ashna D.K. MBChB, Kilabuk Elaine, BA, Brennan Troyen A. MD JD MPH & Choudry Niteesh K. MD PhD Boton MA, New York NY, Ontario Canada, Woonsocket RI; Gender and Racial Disparities in adherence to statin therapy: A Meta-analysis http://dx.doi.org/10.1016/ahj.2013.02.011
  6. Elliot Josh CTV News Study links Statins to Higher Diabetes Risk, May 29, 2014: http://www.ctvnews.ca/health/study-lins-statins-to higher-diabetes-risk-1.1843765
  7. Nielson Sune Fallgaard & Nordestgaard Borge Gronne: Negative statin-related news stories decrease statin persistence and increae myocardial infarction and cardiovascular mortality: a nationwide cohort study: European Heart Journal (2016) 37, 908-916 ; doi:10.1093/euroheartj/ehv641
  8. News (http://creakyjoints.org/category/news/) Stopping Statin Therapy increases Risk of Death for Rheumatoid Arthritis Patients; https://creakyjoints.org/news/stopping-statin-therapy-increases-risk-death-rheumatoid-arthritis-patients/.

The articles, on the Cardiac Health Foundation of Canada website, are presented with the understanding that the Foundation is providing information only and not rendering medical advice. Please check with your family physician, specialist or health care professional before implementing any of the ideas expressed in these articles.