Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy

Abstract

Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; AIM-HIGH ClinicalTrials.gov number, NCT00120289.).

National Trends in Nonstatin Use and Expenditures Among the US Adult Population From 2002 to 2013: Insights From Medical Expenditure Panel Survey

“…Over the study period, total gross domestic product‐adjusted costs associated with nonstatins peaked at more than $9 billion in 2008‐2009. The slightly lower rates of nonstatin LLT use seen since then may have been due to a series of trials mostly demonstrating no cardiovascular outcome benefits of nonstatin LLT 3, 4, 5. However, despite weak evidence for clinical improvement from fibrates and net harm from niacin, in 2012‐2013 they accounted for $2.5 billion and $873 million in annual national expenditure, respectively.…”

“…This was highlighted in the 2013 American Heart Association/American College of Cardiology guidelines for cholesterol management, which reflected weak evidence for nonstatin medications observed by several randomized controlled trials, including ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression),3 AIM‐HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcome),4 and ACCORD (Action to Control Cardiovascular Risk in Diabetes) 5. However, a recently published American College of Cardiology expert consensus document, written after the publication of IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)6 and FOURIER (Further Cardiovascular Outcomes Research With PCK9 Inhibition in Subjects With Elevated Risk),7 provides clinical guidance for nonstatin use but noted that the evidence base for the various agents is heterogeneous given that several medications in this class such as niacin, fibrates, and bile acid sequestrants lack strong contemporary evidence 8.…”

PCSK9 Inhibitors in Lipid Management of Patients With Diabetes Mellitus and High Cardiovascular Risk: A Review

“…In the IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) trial evaluating the addition of ezetimibe concomitant with statin therapy, which lowered LDL‐C levels below previous targets to a median level of 53 mg/dL in 18 144 patients with recent acute coronary syndromes (27% of whom had diabetes mellitus),11 individuals with diabetes mellitus had significantly greater relative and absolute benefit in improved cardiovascular outcomes than those without diabetes mellitus 14. Clinical outcomes studies for niacin (AIM‐HIGH [Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes] and HPS2‐THRIVE [Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events]) and fenofibrate (ACCORD [Action to Control Cardiovascular Risk in Diabetes] and FIELD [Fenofibrate Intervention and Event Lowering in Diabetes]) did not demonstrate significant cardiovascular benefits in individuals with diabetes mellitus, although there was a suggestion of benefit in subgroups with very high triglyceride levels in the fenofibrate studies 15, 16, 17, 18. Because of increased risk of adverse events (AEs) and lack of evidence of meaningful benefits as seen in cardiovascular outcomes trials,15, 16, 17 the US Food and Drug Administration (FDA) has recently rescinded its approval of the combined use of statins with niacin extended‐release tablets or fenofibric acid delayed‐release capsules 19.…”

“…Clinical outcomes studies for niacin (AIM‐HIGH [Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes] and HPS2‐THRIVE [Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events]) and fenofibrate (ACCORD [Action to Control Cardiovascular Risk in Diabetes] and FIELD [Fenofibrate Intervention and Event Lowering in Diabetes]) did not demonstrate significant cardiovascular benefits in individuals with diabetes mellitus, although there was a suggestion of benefit in subgroups with very high triglyceride levels in the fenofibrate studies 15, 16, 17, 18. Because of increased risk of adverse events (AEs) and lack of evidence of meaningful benefits as seen in cardiovascular outcomes trials,15, 16, 17 the US Food and Drug Administration (FDA) has recently rescinded its approval of the combined use of statins with niacin extended‐release tablets or fenofibric acid delayed‐release capsules 19. These nonstatin therapies only produce moderate LDL‐C‐lowering effects and have side effects that limit their use 11, 15, 16, 17…”

“…Because of increased risk of adverse events (AEs) and lack of evidence of meaningful benefits as seen in cardiovascular outcomes trials,15, 16, 17 the US Food and Drug Administration (FDA) has recently rescinded its approval of the combined use of statins with niacin extended‐release tablets or fenofibric acid delayed‐release capsules 19. These nonstatin therapies only produce moderate LDL‐C‐lowering effects and have side effects that limit their use 11, 15, 16, 17…”