PATIENT EDUCATION

Why doctors prescribe statins

How a half a billion-year war between ancient
bacteria and fungi have helped to lower
cholesterol and become a new weapon
to fight cancer

About 40 million adults in the U.S. take a statin to lower their cholesterol and to reduce their risk of heart disease, heart attack, or stroke. New research suggests a possible anti-cancer benefit for statins. Dr. Robert Benton, Director of Research at Capital Cardiology Associates, explains how statins became one of the standard medications prescribed for heart health.

The link to lowering cholesterol production

Some say the history of statins in medicine begins with Virchow, the German pathologist and one of the 19th century’s foremost leaders in medicine and pathology. He discovered a yellow, fatty substance on the artery walls of patients dying of heart disease or a heart attack before the turn of the century. That plaque was later identified as cholesterol. At that time, physicians were not convinced of the link between cholesterol and coronary heart disease. That connection would not be made until the 1950s.

The Seven Countries Study, initiated in the 1950s, brought together researchers from all over the world. It became a collective effort to study their common questions about heart and vascular diseases among countries with different traditions in diets and lifestyles. This study focused on coronary disease and cholesterol in Italy, Spain, South Africa, and Japan from 1952 to 1956 and Finland, Italy, and Greece from 1956 to 1957. We learned that cholesterol, blood pressure, diabetes, and smoking are universal risk factors for coronary heart disease. The discovery was made that when the body makes too much cholesterol, there is a higher risk of heart disease, heart attack, or stroke.

Researchers began studying how to lower cholesterol to benefit patients. They tried using diet modifications at first, promoting the eating pattern they found in Italy and Greece in the 1950s and 60s, now popularly called “The Mediterranean Diet.” By the mid-1960s, scientists were exploring for ways to alter how cholesterol was produced, chemically. In the 1970s, a microbiologist in Japan, Akira Endo, added research into how antimicrobial agents reduced cholesterol. “It’s almost like the discovery of penicillin. You find the effect of one organism on another and use that to attack a problem. This is a similar thought process that led to finding statins,” noted Dr. Benton. By 1978, the first statin, lovastatin, was discovered.

What is a statin

“A statin is an enzyme that works in your liver to help you make cholesterol, usually at night. What the statins do as a class of medicine, is prevent that long chain of metabolic steps from being completed,” explained Dr. Benton. By the mid-1980s, lovastatin became available for prescription use and was able to reduce LDL cholesterol, producing very few side effects effectively. “I don’t remember my first statin prescription; it was probably in medical school in the early 1990s. When I became a cardiologist, that’s when statins became standard in the care of patients. There were other medicines that we used before that which were not as effective,” recalled Benton.

Simvastatin (Zocor) was the second statin used clinically. Pravastatin (Pravachol) followed in 1991, fluvastatin (Lescol) in 1994, atorvastatin (Lipitor) in 1997, cerivastatin (Baycol, Lipobay) in 1998, and rosuvastatin (Crestor) in 2003. “What happens is there is one chemical entity, and science tries to make it better. Can it be better absorbed, lasts longer, have a better target, or durability? Clinical trials then test to see if it’s safe and effective in lowering cholesterol and heart disease endpoints. That’s how you make the progression through the different statins that have been prescribed over time,” outlined Dr. Benton. Today, statins are one of the most common medicines prescribed in the U.S., with about 40 million people taking them. “Statins are clearly the first-line therapy along with modifications in diet and exercise in lowering cholesterol. Certainly, for secondary prevention, a person who has had a heart attack or stroke should be on a statin. A person with diabetes should be on a stain. These are generic medicines that do not cost very much,” states Benton.

Statin controversy

For a 42-year old drug, statins have had their fair share of reviews and criticism. A bitter dispute erupted in September of 2016 among doctors over suggestions that statins should be prescribed to millions of healthy people at low risk of heart disease. The controversy focuses on who should receive statings and how common/serious are the side effects. Dr. Benton is well aware of the conflict, “like any medicine; there is a risk/benefit profile. I think there is no controversy for being on a statin for secondary prevention after a cardiac or vascular event – that’s not an issue.” In 2013, a joint task force of the American College of Cardiology and the American Heart Association released guidelines for treating cholesterol. These guidelines focused on treating the patient based on his or her risk of developing heart disease, not a target number.

GROUP I

People without cardiovascular disease who have risk factors for the disease and a higher 10-year risk of a heart attack. This group includes people who have diabetes, high cholesterol, high blood pressure, or who smoke and whose 10-year risk of a heart attack is 7.5 percent or higher.

GROUP II

People who already have cardiovascular disease related to hardening of the arteries (atherosclerosis). This group includes people who have had heart attacks, strokes caused by blockages in a blood vessel, ministrokes (transient ischemic attacks), peripheral artery disease, or prior surgery to open or replace coronary arteries.

GROUP III

People who have very high LDL (bad) cholesterol. This group includes adults who have LDL cholesterol levels of 190 mg/dL (4.9 mmol/L) or higher.

GROUP IV

People who have diabetes. This group includes adults who have diabetes and an LDL between 70 and 189 mg/dL (1.8 and 4.9 mmol/L), especially if they have evidence of vascular disease or other risk factors for heart disease such as high blood pressure, smoking or being older than age 40.

The most common side effect of statins is muscle ache or pain. “Somewhere around 5 to 10% of people have muscle ache or myalgia. That’s real,” said Dr. Benton. Typically, aches and pain can be eliminated by changing the dose, frequency, or type of statin. Please talk with your doctor about your concerns as they can usually find a statin that you can tolerate without side effects. “There are people who are at a predisposition to have mild muscle aches. In extreme rare occurrences, there is dissolution of the muscles, they become destroyed, but that is a sporadic occurrence.”

There is a controversial link between statins and memory loss. A John Hopkins review of dozens of studies on the use of statin medications to prevent heart attacks shows that the commonly prescribed drugs pose no threat to short-term memory and that they may even protect against dementia when taken for more than one year. “All medications, including stat-ins, may cause side effects, and many patients take multiple medicines that could theoretically interact with each other and cause cognitive problems,” says Kristopher Swiger, a primary author of the study. In 2015, the U.S. Food and Drug Administration (FDA) made labeling changes to statins to outline the potential for non-serious and reversible side effects, which include: memory loss and confusion, increased blood sugar, increased hemoglobin A1c levels.

Statins anti-cancer properties

Doctors at Duke University School of Medicine in Durham, North Carolina investigated whether statin use affected outcomes in veterans at a VA Medical Center who had been diagnosed with colorectal cancer. They found that after five years, those taking a statin were 38% less likely to die from colorectal cancer. How does a cholesterol drug fight cancer? Dr. Benton explained how statins block the same enzyme the body needs to make cholesterol, called HMG-CoA. This process also slows cancer cell growth. “There are multiple enzymes in cancer cells. Statins, as a class of medicines, have many different targets that they work on. Any type of chemical entity that would interfere with that pathway of growth is probably a method of preventing cancer cells from progressing. I don’t think you are going to find people treating cancer with statins; it may be an off-target approach. You need cancer medicines, chemotherapy or biologics, or radiation, but statins may have some augmented type of function.” Research is also underway on the anti-cancer properties using statins and the diabetes drug metformin (often prescribed together) in men with prostate cancer. Men who took both drugs in a study lived longer than those who only took the statin or those who didn’t take either drug. Researchers believe the drug combo may help slow the growth process of prostate cancer. Expect to see more news on clinical trials using either metformin or a statin in cancer treatment in the coming months.

Written by Michael Arce, Marketing Coordinator