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Current Drug Options for Raising HDL Cholesterol
Richard L Dunbar1, Daniel J Rader
1University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia, PHI building, Suite 351, 39th and Market Streets, Philadelphia, PA 19104, USA. richard.dunbar@uphs.upenn.edu.
Insights
Raising high-density lipoprotein cholesterol (HDLC) lacks definitive event-based trial data. Therapy decisions for low HDLC focus on cardiovascular risk, often involving statins and potentially niacin or fibrates for high-risk individuals.
Area of Science:
- Cardiology
- Metabolic Disorders
- Pharmacology
Background:
- Low high-density lipoprotein cholesterol (HDLC) is linked to cardiovascular risk, but evidence for HDLC-raising therapy benefits is limited.
- Current dyslipidemia guidelines prioritize low-density lipoprotein cholesterol (LDLC) and non-HDLC targets.
- The decision to target low HDLC is based on individual cardiovascular event risk assessment.
Purpose of the Study:
- To review the current evidence and clinical considerations for high-density lipoprotein (HDL)-raising therapy in patients with low HDLC.
- To outline therapeutic strategies for managing low HDLC in various cardiovascular risk groups.
Main Methods:
- Review of existing clinical guidelines and evidence regarding HDLC management.
- Analysis of pharmacologic approaches for increasing HDLC levels.
- Discussion of risk stratification for guiding HDLC-targeted therapy.
Main Results:
- Statins are primary therapy for LDLC and non-HDLC goals, often benefiting patients with low HDLC.
- Niacin or fibrates may be added to statins for significant HDLC elevation in high-risk patients.
- No formal HDLC goals exist, but target levels are generally >40 mg/dL (men) and >50 mg/dL (women).
Conclusions:
- Pharmacologic intervention to raise HDLC is primarily considered for high-risk patients (e.g., established vascular disease, diabetes, high Framingham score).
- Therapy for moderate-risk patients with low HDLC requires careful individualization.
- Further event-based trials are needed to definitively establish the benefit of HDL-raising therapies.
Abstract:
Although circumstantial evidence supports raising high-density lipoprotein cholesterol (HDLC) in patients with low levels of HDLC, the scarcity of event-based trials has led to uncertainty with regard to the benefit of high-density lipoprotein (HDL)-raising therapy. Based on the National Cholesterol Education Program guidelines, therapy for dyslipidemia is focused initially on targeting low-density lipoprotein cholesterol (LDLC), and in patients with hypertriglyceridemia, secondarily on targeting non-HDLC. When HDLC remains low, the decision to target HDLC depends on the assessment of risk of cardiovascular events. We often consider drug therapy specifically to raise HDLC in high-risk patients, such as those with established atherosclerotic vascular disease, type 2 diabetes, or a Framingham risk score of 20% or above. The majority of high-risk patients require drug therapy, usually a statin, to achieve aggressive LDLC and non-HDLC goals, and thus many patients with low HDLC are candidates for statin therapy. However, a second drug is often required to achieve substantial HDL raising. Although no formal goals for HDLC exist, reasonable goals are HDLC greater than 40 mg/dL in men and greater than 50 mg/dL in women. We often add either niacin or a fibrate to a statin in high-risk patients with low HDLC levels. Targeting HDLC with pharmacologic therapy is a more difficult decision in moderate-risk patients, in whom therapy must be highly individualized.
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