High or abnormal cholesterol levels, inflammation, and endothelial dysfunction play key roles in atherosclerosis and plaque build-up, the leading cause of heart attacks and strokes. (Endothelial dysfunction refers to a dysfunction of the inner lining of blood vessels on the surface of the heart. This causes these vessels to inappropriately narrow rather than dilate, restricting blood flow.) There are many different types of cholesterol, including lipoprotein high density (HDL) or good, cholesterol); Triglycerides (a by-product of excess calories stored as fat); and low density lipoprotein (LDL or bad cholesterol).
It is common knowledge that lowering LDL cholesterol, sometimes whether or not you have high cholesterol, improves cardiovascular outcomes. But do older adults benefit from lowering cholesterol and are they at additional risks?
Lowering LDL reduces cardiovascular risk
Studies have consistently shown that lowering LDL cholesterol reduces the risk of cardiovascular death, heart attack, stroke, and the need for cardiac catheterization or bypass surgery. This has been shown in patients with established coronary artery disease as well as in high risk patients without coronary artery disease.
Lifestyle changes can lower cholesterol levels by around 5% to 10%, while cholesterol lowering drugs can lower LDL cholesterol by 50% or more. While lifestyle changes such as a heart-healthy diet (e.g. the Mediterranean Diet), smoking cessation, regular exercise, and weight loss are critical to reducing cardiovascular risk, medication is often needed to provide additional cardiovascular protection Offer.
Statins, including atorvastatin (Lipitor), simvastatin (Zocor), rosuvastatin (Crestor), and pravastatin (Pravachol), are the main therapy for lowering LDL. Statins work by reducing your body’s production of cholesterol, which increases the absorption of LDL, which is circulated in the blood by the liver. But not all of the benefits of statins can be explained by a decrease in LDL alone. Studies show that statins have beneficial effects on inflammation, endothelial dysfunction, and plaque stabilization (when plaque breaks up, it can cause a heart attack or stroke). Statins have been around for about 40 years, so we have some information on their short- and long-term safety and effectiveness.
Ezetimibe (Zetia) is another type of LDL lowering drug. Taken as a pill, it lowers cholesterol levels by blocking absorption in the small intestine. Ezetimibe is mainly used as an add-on drug to statins to achieve further LDL lowering, or on its own in people who cannot tolerate statins. In older adults, ezetimibe alone was found to reduce cardiovascular events but not stroke.
PCSK9 inhibitors are a newer class of cholesterol lowering drugs. They work by leaving more LDL receptors in the liver, which allows the liver to sweep more LDL cholesterol out of the bloodstream. PCSK9 inhibitors have been shown to lower LDL cholesterol by about 60%. There are two PCSK9 inhibitors on the market, evolocumab (Repatha) and alirocumab (Praluent), and both must be taken by injection every few weeks.
LDL Lowering Therapies: Are They Safe For Older Adults?
The clinical benefit of lowering LDL cholesterol in older adults has been controversial, as people aged 75 and over are typically not included in large numbers in clinical trials. Some have even argued that the risks of LDL lowering treatment might outweigh the benefits for older adults compared to younger adults. But the evidence debunks this myth.
Meta-analyzes and clinical studies show that statin use is not associated with an increased risk of muscle injury, cognitive impairment, cancer, or hemorrhagic stroke, regardless of age, compared to those who do not use statin. Likewise, in clinical trials, the risk of liver or kidney injury in people taking statins or a placebo is similar regardless of age. A prospective study evaluating liver safety in the very elderly found that statins are overall safe in patients 80 years and older.
The most common side effect of statins is muscle pain, which affects less than 1% of patients. Even if one type of statin causes side effects in a person, another statin cannot. Statins can increase blood sugar, but it is unlikely to lead to type 2 diabetes in people who are not already at high risk for the disease. Similarly, ezetimibe is largely safe to use, with diarrhea and upper respiratory infections being the most common side effects. In particular, the safety profile for ezetimibe plus statins is the same as for statins alone, even in older adults. Finally, PCSK9 inhibitors have not been found to increase the risk of diabetes, neurocognitive disorders, liver or muscle injuries.
Evidence for LDL-Lowering Therapies in Older Adults
The question remains: do the benefits of cholesterol lowering treatments outweigh the risks for older adults? In a systematic review and meta-analysis published in The lancetResearchers evaluated the clinical benefit of statin and non-statin cholesterol lowering therapy for older adults. To do this, they extracted and analyzed data from previous studies evaluating treatments to lower statin and non-statin cholesterol. The analysis included 21,492 patients aged 75 and over. Of these, 54.1% of the patients had been included in statin studies; 28.9% in ezetimibe studies; and 16.4% in PCSK9 inhibitor studies.
Investigators made these important observations:
- Elderly patients are 40% more likely to have serious cardiovascular events than younger patients (5.7% versus 4.1%).
- For every 38 mg / dL lowering of LDL cholesterol in elderly patients taking LDL-lowering therapies, the risk of serious cardiovascular events was reduced by 26%.
- The lowering of LDL prevented cardiovascular events in older and younger adults to a similar extent.
- In older adults, statin and non-statin LDL lowering therapies were similarly effective in preventing most major cardiovascular events. The exception was a stroke, where non-statin therapy was slightly more effective; This is likely due to the use of PCSK9 inhibitors.
Most of the above analysis represented elderly patients with pre-existing cardiovascular disease. There are ongoing studies that will help evaluate the utility of statins in elderly patients as primary prevention for major cardiovascular events.
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