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Statins

In my six-plus decades, I have been living with the conundrum of cholesterol. The word conundrum fits my fascination with cholesterol perfectly. Per the Merriam-Webster dictionary, the meaning of conundrum is “a difficult or intricate problem or a riddle whose answer is or involves a pun.” I always remember the Dave Barry quote: “It is a scientific fact that your body will not absorb cholesterol if you take it from another person’s plate.”

Cholesterol is a lipid molecule produced in animal cells and is a component of all cell membranes. Cholesterol is necessary to produce bile acids that help the digestion of food. Cholesterol is also necessary to produce steroid hormones and vitamin D in the body.

Cholesterol was first isolated from gallstones in 1784. Thirteen Nobel prizes have been awarded to scientists doing cholesterol research. The lipid was not linked to the deposition and forming of plaques in arteries until the 1940s.

We are bombarded with information in magazines, TV, and the Internet concerning our health and the role of cholesterol. LDL, HDL, and total cholesterol levels should be tested in men over 35 and women over 45 years of age.

In normal digestion, the body will use the cholesterol it needs and then ship the leftovers over to the liver for elimination. Low Density Lipids (LDL), if in excess, will be deposited in the coronary arteries and become a plaque. High Density Lipids (HDL), as I was taught, are your “scrubbing bubbles” that scour away the LDL and send it to the liver. A high HDL level is good, but I have not found any data or studies in the medical literature to prove that. I was taught that having patients take niacin in high doses increases HDL, and lowers triglycerides and LDL levels. There is very little data, however, proving that it decreases the risk of heart attack or stroke in patients.

In 1987, statins were added to niacin and bile acid sequestrants as agents to decrease cholesterol levels. Statins work by reducing LDL cholesterol and other lipoproteins circulating in the blood. Statins cause the liver to produce more LDL receptors, therefore grabbing more LDL from the blood. It was also discovered that statins are anti-inflammatory and decrease plaque size and formation. A patient taking a statin will start seeing the full benefits to their cardiac health in a few months. In the mid-2000s, a study was done giving two doses of Atorvastatin (Lipitor®) before the patient went for cardiac catheterization. This study showed an 88% risk reduction of major cardiac events at 30 days (ARMYDA-ACS JACC Vol 49, Issue 12, March 2007).

The new cholesterol guidelines were released November 10, 2018, from the American College of Cardiology/American Heart Association. Some noteworthy changes were adding family history, ethnicity, chronic kidney disease, and high lipid biomarkers to high blood pressure, smoking, and high blood sugar as risk factors for a coronary event. In children between the ages of 9 and 11 and 17 and 21 who have a family history of heart disease or high cholesterol, an elective cholesterol screening may be necessary. This really hits me right in the stomach, as I remember my dietary habits of visiting fast food restaurants on a regular basis between the ages of 9 and 21 years of age.

The first statin on the market back in September 1987 was lovastatin (Mevacor®). The trial was called AFCAPS/TexCAPS, Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels (JAMA 1998;279(20):1615-1622).

This study showed a 37% risk reduction of having a major cardiovascular event. Lovastatin was followed by simvastatin (Zocor®), fluvastatin (Lescol®), pravastatin (Pravachol®), atorvastatin (Lipitor®), pitavastatin (Livalo®), and rosuvastatin (Crestor®). Every statin listed here is on the FAA Accepted Medications Database as approved for use while flying.

The statin studies have shown over these many years that the lower the LDL the better. The gold standard goal LDL level has gone from 160, to 100, to 70, and now it is at 50 for high-risk patients. I was involved in a study called IMPROVE-IT, where simvastatin was combined with ezetimibe (Zetia®), a drug that decreases absorption of cholesterol in the gut. In 18,144 patients there was a 2% absolute risk reduction of cardiovascular events and the LDL was lowered to 50 with the combination of simvastatin/ezetimibe (N Engl J Med 2015; 372:2387-2397).

Statins are approved both for primary and secondary prevention for cardiovascular events. Primary prevention means the patient has risk factors like smoking, high blood pressure, and abnormally high lipid levels with no diagnosed cardiovascular disease. Administering a statin would reduce the risk in this patient for a heart attack. Secondary prevention means the patient has cardiovascular disease and administering a statin will decrease the risk for a heart attack as well.

The side effects of statins are muscle aches and pains, liver damage, and rhabdomyolysis. Rhabdomyolysis is a breakdown of skeletal muscle. This happens very rarely with statins. Muscle aches and pains happen about 10% of the time and the remedy for that is to change to a different statin or decrease the dose of the present statin.

The big controversy with statins is the FDA claims of causing diabetes, liver disease, and changes in cognitive function and memory loss or dementia. The claim that statins cause memory loss or dementia has never been studied. Some folks taking statins will report a “fuzzy feeling” while taking them. This is easily remedied by decreasing the dose of the statin or switching to a different one. There are ongoing studies showing dementia is caused by atherosclerosis. Taking a statin decreases atherosclerosis and would therefore decrease the risk for dementia. So the FDA claim is a little fuzzy for me to understand. No, I am not on a statin.

Statins may increase the body’s blood sugar. The patients who need to take statins are at a high risk of getting diabetes due to their poor diet, exercise, and family history. Some patients who get prescribed a statin come into their physician’s office and have underlying pre-diabetes. The blood sugar goes up due to both the statin and the pre-diabetic state. The statin gets blamed as the cause.

The liver toxicity of statins is very small. In the beginning when lovastatin came onto the market, the patient had to get liver enzyme testing every 3 months. That proved to be a waste of time and money. Liver enzyme testing has been stopped unless the patient is showing signs of liver disease.

In the right patients, statins save lives, decrease the risk for stroke, and act as an anti-inflammatory. The benefits far outweigh the risks especially when it comes to stopping and reversing cardiovascular disease with a statin combined with a healthy lifestyle. Fellow pilots, if you are a candidate for a statin or are already on a statin, know that the data is behind you to keep you flying for a very long time to come.

Larry M. Diamond, PharmD, CFII

Larry Diamond has a Doctor of Pharmacy Degree and has been a pharmacist for 37 years. Larry’s pharmacy practice has been as a Clinical Pharmacy Specialist in Cardiology, Orthopedic Surgery Specialist and most recently Clinical Pharmacy Coordinator. He is a CFII, a pilot for 33 years and has been an AOPA member since 1984.

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