Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients

Abstract

Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).

Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease

“…Currently, no treatment option has been established for high Lp(a) levels, other than experimental and observational regimes 27, 28, 29, 30, 31, 32, 33. Moreover, to date, no randomized controlled trials have directly evaluated the effect of lowering Lp(a) on cardiovascular outcomes including AS development.…”

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

“…Among these 59 surrogate endpoint trials that had a subsequent clinical endpoint trial, in 24 cases the clinical endpoint trial results validated the positive surrogate trials, while in 20 the subsequent clinical endpoint trial was negative (Table 3). 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 A negative surrogate endpoint trial was less likely to be followed by a positive outcome trial and we identified only 3 such examples ( P =0.02, Figure 2). …”

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…”