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A 52-year-old male, with no known cardiovascular risk factors, has a history of a non–ST-elevation myocardial infarction (NSTEMI) one year ago. His lipid levels prior to that event were: total cholesterol 200 mg/dL, high-density lipoprotein cholesterol (HDL-C) 45 mg/dL, triglycerides 140 mg/dL, and low-density lipoprotein cholesterol (LDL-C) 127 mg/dL. He has been taking atorvastatin 80 mg/day and aspirin 81 mg/day since that event.
He presents to the emergency department with evidence of another NSTEMI. His blood pressure is 118/70 mm Hg, and his body mass index (BMI) is 26. He has no smoking history and no known glucose intolerance. He has no family history of premature coronary heart disease (CHD), but he has no siblings and his father died of cancer at age 54. His current lipid levels on atorvastatin are: cholesterol 140 mg/dL, HDL-C 45 mg/dL, triglycerides 150 mg/dL, and LDL-C 65 mg/dL. Specialized lipid tests were obtained, showing apoliprotein B (ApoB) 95 mg/dL, LDL-P (by NMR) 1,180, and lipoprotein(a) (Lp[a]) 102 mg/dL (total particle mass measurement). Cardiac catheterization showed diffuse three-vessel disease.
Which of the following statements describes your recommendation for further lipid therapy?
Show Answer
The correct answer is: D. Add ezetimibe 10 mg/day and extended-release niacin 2,000 mg/day.
Lipoprotein(a) is a genetically-determined lipoprotein that is both atherogenic and may enhance thrombosis. Genetic studies suggest that the LPA gene is causally related to coronary heart disease, and to a risk for aortic stenosis.1 The vast majority of people do not have a high Lp(a) level; however, observational data show that levels >50 mg/dL (the 80th percentile of the population) are associated with at least a 50% greater relative risk for coronary heart disease.2,3 The European Atherosclerosis Society (EAS) has recommended testing for Lp(a) in cases of premature coronary heart disease, a family history of premature coronary heart disease, cases of familial hypercholesterolemia (FH), or if recurrent events occur on optimal medical therapy.4,5,6 Two of these indications apply to this patient. Statins, ezetimibe, bile acid resins, fibrates, and omega 3 fatty acids do not reduce Lp(a). Niacin can reduce Lp(a) by as much as 25% at 2,000 mg/day. Recent data from the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2–THRIVE) and Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trials have questioned the safety of extended-release niacin at 2,000 mg/day added to a statin compared to the limited outcomes benefit. While most of these adverse events are known issues with niacin (glucose intolerance, increased liver enzymes, gastrointestinal [GI] tolerance and flushing), a few were new (infections and bleeding).9,10 Clinical judgment should be used in deciding upon the risk versus benefit of adding niacin in individual patients. Repetitive LDL apheresis can acutely reduce Lp(a) by 50-60% and time-averaged reductions can be 30-40%.7 There are two investigational lipid drugs that can lower Lp(a) (cholesteryl-ester-transfer protein [CETP] inhibitors and anti-proprotein convertase subtilisin/kexin type 9 [PCSK9] monoclonal antibodies8), but they are not available yet. There are two drugs recently approved for the rare homozygous FH patient, mipomersen and lomitapide, that can reduce Lp(a) by 25% but are not approved for that indication alone. This patient on maximum dose of atorvastatin, which is evidenced-based therapy, still has a high ApoB and LDL-P compared to his LDL-C level (referred to as discordance), and the best recommendation for him, with recurrent events, is to reduce the ApoB-containing lipoproteins as much as possible. This is consistent with the EAS recommendations and can be achieved by adding ezetimibe and niacin in order to get ApoB <80 mg/dL and LDL-P <1,000, as well as reducing his Lp(a) by up to 25%.
References
Tharassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcifications and aortic stenosis. N Eng J Med 2013;368:503-12.
Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentrations and the risk of coronary heart disease, stroke and nonvascular mortality. JAMA 2009;302:412-23.
Kamstrup PR, Benn M, Tybjaerg-Hansen A, et al. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation 2008;117:176-84.
Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. Eur Heart J 2010;31:2844-53.
Alfonso R, Andres E, Mata N, et al. Lipoprotein(a) levels in familial hypercholesterolemia: An important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol 2014;63:1982-9.
Ezhov MV, Safarova MS, Afanasiera OJ, et al. Lipoprotein(a) level and apolipoprotein(a) phenotype as predictors of long term outcomes after coronary artery bypass grafting. Atherosclerosis 2014;235:477-82.
Leebman J, Roeseler E, Julius U, et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a) hyperlipoproteinemia and progressive cardiovascular disease. Circulation 2013;128:2567-76.
Raal FJ, Giugliano RP, Sabatine MS, et al. Reduction in lipoprotein (a) with PCSK9 monoclonal antibody Evolocumab (AMG 145): A pooled analysis of more than 1300 patients in 4 phase II trials. J Am Coll Cardiol 2014;63:1278-88.
HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-12.
AIM-HIGH Investigators. Safety of extended-release niacin in the AIM-HIGH trial. N Engl J Med 2014;371:288-90.
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