How and why can safety, compliance & motivation towards therapy with statin drugs be achieved and maintained in those over 70? Especialy when we have one side saying that statins drugs do not pose a safety risk for the elderly. And the other side saying that statins, and antihyperlipidemic drugs, are associated with multiple side effects, adverse reactions, and drug-drug interactions.
On one side, the American Medical Directors Association (AMDA) says, there is no supporting evidence that individuals with a limited life expectancy (defined as those over 70 years old) can benefit from routine prescribing of lipid-lowering medications in the long-run (Graham, 2013). Especially if they do not have pre-exising cardiovascular disease (CVD). The AMDA stated that routine prescribing may cause more harm than good. The FDA requires drug companies to label statin drugs with indication of the possible risk for memory loss, diabetes, and other complications (U.S. Food and Drug Administration, 2012).
On the other side, studies have suggested that statin drugs may slow the progression of dementia, metabolic disease, and peripheral vascular disease; and prevent bone fractures. A study of people aged 80 to 97 with established coronary artery disease found there was a 50% relative risk reduction in total mortality in patients receiving statin therapy (Morley, 2011). While a meta-analysis of controlled studies concluded that in elderly subjects at high CVD risk without established CVD, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term (Saverese et al, 2012). This suggests that statins can preserve quality of life for those at risk for CVD, and length of life for those with CVD.
None of the other drugs are as effective as HMG-CoA Reductase Inhibitors (statins) in lowering LDL. The goal is 70 to 100 mg/dl. Statins lower LDL levels anywhere from 10 to 60%; modestly increase HDL level by 5 - 23%, and modestly decrease TG by 10 - 30% (Edmunds & Mayhew, 2013). In order of their increasing strength to lower LDL: fluvastatin (Lescol), lovastatin (Mevacor), simvistatin (Zocor), atrovastatin (Lipitor), and rosuvastatin (Crestor). Statins also decrease C-reactive protein (CRP) which is another marker for cardiovascular disease. Most statin drugs, if not all, are dosed once a day at mealtime or bedtime. See ATP III Guidelines.
Headache, GI complaints, muscle pain are some of the side-effects which may hinder compliance if not tolerated or managed. Liver, renal and muscle toxicity (rhabdomyolysis) are the major adverse reaction common to all statins. Hence, liver and renal impairment are the main comorbidities where statins drugs are contraindicated or used with caution. Drug-drug interactions include many drugs that the elderly are not likely to be taking on a daily basis (with the exception of verapramil, and diltiazam). All statins have dosing limits or contraindication with protease inhibitors (Edmunds & Mayhew). Grapefuit juice and eucalyptus essential oil are the major food and herbs to avoid. Both of these are notorious for enhancing the cytochrome P450 enzyme system.
Combination therapy with antihyperlipidemics increases the risk for adverse reactions from any one of them individually. Acupuncture, Chinese herbal medicine, and food as medicine can be use as adjunctive therapy to minimize the need for combination therapy (see Part 2). Here are the six classes of antihyperlipidemics drugs that are used in combination (Edmunds & Mayhew, 2013):
HMG-CoA Reductase Inhibitors (statins) are for primary hyperlipidemia with elevated cholesterol (secondarily for elevated TG).
Fibric Acid Derivitives decrease the risk for CHD in those without history of CHD. They increase HDL, and lower markedly high TG (associated with pancreatitis). They do not lower LDL, and may increase LDL.
Bile Acid Sequesterants are used in adjunct to diet to reduce LDL in those with primary hypercholesterolemia. They are not absorbed systemically, thus are very safe, but they taste bad, and may cause GI upset. They can bind with other drugs in the GI tract, thus are taken separately.
Nicotinic Acid (Niacin, Niaspan) is used for all types of hyperlipidemia (triglycerides and total cholesterol). It lowers LDL, but is more effective at lowering TG, and increasing HDL. "Niacin flush" is an uncomfortable but transient side effect. It can impair glycemic control, and is used with caution with liver impairment and peptic ulcers. Some side effects are dose related.
Selective Cholesterol Absorption Inhibitor decreases GI absorpton of cholesterol by 50%. It is used as monotherapy in adjunct to diet to lower LDL and TG, and increase HDL. The LDL lowering effect is potentiated by 18% when taken with a statin. Ezetimbide is the only drug in this class.
Lovaza is a combination of two omega 3 fatty acids (EPA & DHA) from fish oil. It is used in adjunct to diet for very high TG (>500mg). It can reduce TG by 45%, but may be associated with a rise in LDL, with no effect on HDL. Caution is used with those on anticoagulants.
INTEGRATIVE MEDICINE TIP: A Framingham Risk Score is an easy way to calculate a patients risk for cardiovascular event (e.g. heart attack, stroke) within the next 10 years. It is an online widget that uses age, smoking status, HDL, and systolic blood pressure. A score of 20% or greater indicates risk for a cardiovascular event in 10 years, with the need for primary care & prevention.
Edmunds, M., & Mayhew, M. (2013). Pharmacology for the primary care provider (4th ed). St.
Louis, MO: Elsevier Mosby.
Graham, J. (October, 22, 2013). Controversy over statins for older patients. New York Times
Morley, J. (2011, October). The cholesterol conundrum (editorial). Journal of the American
Geriatrics Society, 59(10), 1955-1956. doi:10.1111/j.1532-5415.2011.03594.x
Saverese, G. et al. (2012). Benefits of statins in elderly subjects without established
cardiovascular disease: a meta-analysis. American Journal of Cardiology 62(22), 2090-9.
doi: 10.1016/j.jacc.2013.07.069. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23954343
U.S. Food and Drug Administration. (2012). FDA news release: FDA announces safety changes in
labeling for some cholesterol-lowering drugs. Retrieved from http://www.fda.gov/Ne