From the Guidelines
If your cholesterol and LDL levels are very low while on a statin, you should not make any changes to your medication without first discussing it with your healthcare provider. While statins are designed to lower cholesterol, the current evidence suggests that very low LDL-C levels are not associated with significant clinical adverse effects 1. In fact, studies have shown that patients with lifelong low LDL-C levels, such as those with PCSK9 loss-of-function mutations, experience significantly fewer coronary events compared to control groups 1. The European Heart Journal study published in 2021 found that the mechanism of achieving low LDL-C levels, such as through increased LDL-C clearance, appears to have fewer side effects compared to decreased lipoprotein secretion or production 1.
The goal of statin treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL) 1. However, the benefits of statins extend beyond just cholesterol lowering, and any medication changes should balance the risks of low cholesterol against the benefits of continued statin therapy. Some patients may experience side effects with very low cholesterol levels, including muscle pain, cognitive issues, or increased risk of hemorrhagic stroke, though these are relatively rare 1.
- Key points to consider:
- Very low LDL-C levels are not associated with significant clinical adverse effects 1
- The mechanism of achieving low LDL-C levels is important, with increased LDL-C clearance having fewer side effects 1
- The goal of statin treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL) 1
- Regular monitoring of cholesterol levels and discussing any symptoms with your doctor is important
- Cardiovascular benefits of statins extend beyond just cholesterol lowering, so any medication changes should balance the risks of low cholesterol against the benefits of continued statin therapy 1
From the FDA Drug Label
12.2 Pharmacodynamics Inhibition of HMG-CoA reductase by simvastatin acid accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. The answer to the question of low cholesterol and low LDL on statin is that simvastatin can help achieve this by:
- Decreasing plasma LDL-C and total cholesterol
- Accelerating the expression of LDL-receptors
- Increasing the uptake of LDL-C from blood to the liver 2
From the Research
Low Cholesterol and Low LDL on Statin
- The use of statins to lower low-density lipoprotein cholesterol (LDL-C) has been widely studied, with evidence suggesting that high LDL-C levels cause atherosclerotic heart disease 3.
- Current guidelines recommend an LDL-C target of 70 mg/dL for patients at high or very high risk, with epidemiologic studies showing that very low LDL-C levels (lower than 70 mg/dL) are associated with a very low risk of cardiovascular disease 3.
- Analyses of randomized clinical trials have shown a greater benefit in reducing the risk of cardiovascular disease among those with very low achieved LDL (below 40 mg/dL) 3.
- High-intensity statin therapy is associated with a higher rate of transaminase elevations, but no hepatic failure, a very small risk of myopathy, and an increased risk of developing diabetes, although the small increase in the risk of developing diabetes is much smaller than the marked lowering of cardiovascular risk 3.
Statin Intensity and Clinical Outcome
- A study of patients with stable coronary artery disease (CAD) and very low LDL-C found that higher intensity statins were beneficial for cardiovascular outcomes, with statins equivalent to or stronger than atorvastatin 20 mg being more effective than lower intensity statins 4.
- The study found that patients who received higher intensity statins had a lower incidence of major adverse cardiac events (MACE), which were mostly related to a lower incidence of coronary revascularization 4.
- Another study found that adding ezetimibe to statin therapy consistently reduced the risk for cardiovascular events in post-acute coronary syndrome (ACS) patients, irrespective of baseline LDL-C values, supporting the use of intensive lipid-lowering therapy with ezetimibe even in patients with baseline LDL-C <70 mg/dL 5.
Benefits of Low LDL-C
- Epidemiologic studies have shown that very low LDL-C levels are associated with a very low risk of cardiovascular disease 3.
- A study of patients with achieved LDL cholesterol below 30 mg/dL found no increase in the usual adverse events compared to patients with LDL cholesterol levels above 30 mg/dL 3.
- The use of PCSK9 inhibitors, which can reduce LDL-C by 50-60% above that achieved by statin therapy alone, has been shown to reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 6.