For each newsletter we strive to choose topics which are current and controversial. This issue will be no exception. One of the axioms in medicine is “Never be the first nor the last to prescribe a medicine.” There is a lot of wisdom in this simple principal. Being the last to prescribe a medicine implies that one is not keeping up with the science of medicine. On the other hand being one of the first to prescribe a medicine implies practicing in an unproven way. There are many examples in medicine of medications or procedures which initially seemed to be very effective but turned out producing very disappointing results.How Medical Reviewers Define What Is Experimental or Investigational
DUR Pharmacy Could Have Prevented PVC Mistreatments
Two examples illustrate this concept. In the late 1980’s a new medication was introduced to the market which had been developed to treat PVC’S (Premature Ventricular Contractions). PVC’s are premature heart beats which can range from being simply annoying, but innocuous in young, healthy people, to becoming debilitating and even life threatening in some elderly patients.
The medication clearly decreased the frequency of PVC’S. However it also increased the mortality rate of the same population of patients it was developed to help. In other words, what seemed to make sense, i.e., decreasing the mortality rate of elderly patients by decreasing the frequency of PVC’S, did not turn out to be true.
What Was Learned from Hip Replacements
Another example of an unexpected and disappointing result is the case of metal-on-metal hip replacements in the first decade of this century. In the laboratory this type of prosthetic hip had been shown to be capable of withstanding far more compression cycles than the previous types of materials used in prosthetic hips.
However after several years metal on metal prosthetic hips were taken off the market because of the unacceptably high rate of early failure of the joints. It turned out that when the components of the hip were not perfectly aligned as in the laboratory, the surfaces would rub against each other in an asymmetrical way and would produce small flakes of metal, resulting in a condition called metallosis. The condition of metallosis consists of an entire spectrum of undesirable effects ranging from mildly elevated concentrations of certain heavy metals, to severe local tissue destruction and even severe system adverse effects including a decrease in cognitive function. So once again what seemed to be a logical step forward in medicine turned out to a step backwards.
A Recent Need for Medical Use Evaluation
One of the current controversies in medicine is the utilization of a new class of medications called “PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitor antibodies” which have been designed to lower cholesterol, particularly LDL (low density lipoprotein). For many years it has been known that high cholesterol, especially elevated LDL, has been a risk factor for the development of atherosclerotic cardiovascular disease. Other risk factors include a positive family history, age, smoking, diabetes, diet, and lack of exercise. The main methods used to treat elevated LDL levels have been lifestyle changes (diet, exercise, and weight loss) and medications. While there are a number of medications which have been used to treat elevated cholesterol, including niacin, fish oil, red yeast rice, etc., the mainstay of medical therapy has been the class of medications known as statins. The statins lower LDL cholesterol by acting on metabolic pathways in the liver. Their main clinical benefits are in individuals who already have clinical ASCVD (atherosclerotic cardiovascular disease) such as an MI, embolic stroke, peripheral arterial disease, etc.
The “PCSK9 inhibitor antibodies” have clearly been proven to lower LDL cholesterol by acting on metabolic pathways which are different from the pathways effected by statins. They have also been demonstrated to be relatively safe. The problem is that while they have been proven to lower LDL cholesterol, they have not yet been proven in long term studies to change morbidity and mortality secondary to ASCVD.
On the surface it would seem that if the medications lower LDL cholesterol and are safe there should be no problem. However at this point in time there are two problems:
1) The medications are quite expensive and ordinarily would be prescribed for life.
2) As illustrated by the two cases at the beginning of this article, what seems logical is not always factual.
Only time will tell if this becomes an example of:
Just Because “It Makes Sense” Doesn’t Mean it is True!
Bennion D. Buchanan, MD, FACEP, MBA