Hyperlipidemia management: A calibrated approach
Gauge the level of LDL cholesterol and assess risk-enhancing factors for ASCVD—thus setting the table for primary and secondary prevention with medical therapy.
PRACTICE RECOMMENDATIONS
› Use an alternative to the Friedewald equation, such as the Martin–Hopkins equation, to estimate the low-density lipoprotein cholesterol (LDL-C) value; order direct measurement of LDL-C; or calculate non–high-density lipoprotein cholesterol to assess the risk for atherosclerotic cardiovascular disease (ASCVD) in patients who have a low LDL-C or a high triglycerides level. C
› Consider the impact of ASCVD risk-enhancing factors and coronary artery calcium scoring in making a recommendation to begin lipid-lowering therapy in intermediate-risk patients. C
› Add ezetimibe if a statin does not sufficiently lower LDL-C or if a patient cannot tolerate an adequate dosage of the statin. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Options for lipid-lowering pharmacotherapy
Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.17
High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).4
Statins are not without risk: A 2016 report18 estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.18
Ezetimibe, a selective cholesterol-absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.19 ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.4
PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.21,23
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