Abstract
Purpose
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the
United States. Recently published cholesterol treatment guidelines emphasize the use
of statins as the preferred treatment strategy for both primary and secondary prevention
of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin
therapy or those who need additional lipid-lowering therapy is unclear in light of
recent evidence that demonstrates a lack of improved cardiovascular outcomes with
combination therapy. The purpose of this review is to summarize and interpret evidence
that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide
recommendations for use of nonstatin therapies in clinical practice, and to review
emerging nonstatin therapies for management of dyslipidemia.
Methods
Relevant articles were identified through searches of PubMed, International Pharmaceutical
Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin,
omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil,
cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin
9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes.
Only English language, human clinical trials, meta-analyses, and systematic reviews
were included. Additional references were identified from citations of published articles.
Findings
Niacin may reduce cardiovascular events as monotherapy; however, recent trials in
combination with statins have failed to show a benefit. Trials with omega-3 FAs have
failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates
may improve cardiovascular outcomes as monotherapy; however, trials in combination
with statins have failed to show a benefit, except in those with elevated triglycerides
(>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile
acid sequestrant in combination with statin therapy on reducing cardiovascular events.
Ezetimibe–statin combination therapy can reduce cardiovascular outcomes in those with
chronic kidney disease and following vascular surgery or acute coronary syndrome.
Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are
currently being evaluated in ongoing Phase III trials.
Implications
Nonstatin therapies have a limited role in reducing cardiovascular events in those
maintained on guideline-directed statin therapy. In certain clinical situations, such
as patients who are unable to tolerate statin therapy or recommended intensities of
statin therapy, those with persistent severe elevations in triglycerides, or patients
with high cardiovascular risk, some nonstatin therapies may be useful in reducing
cardiovascular events. Future research is needed to evaluate the role of nonstatin
therapies in those who are unable to tolerate guideline-directed statin doses.
Key words
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Article info
Publication history
Published online: September 24, 2015
Accepted:
September 1,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
