Dyslipidemia management in primary prevention of cardiovascular disease: Current guidelines and strategies

Table 1 Fixed-dose strategies

Strategy	ACC/AHA 2013	NICE 2014	VA/DoD 2014
Risk score	PCE to determine 10-yr risk of non-fatal and fatal hard ASCVD events (CHD and CVA)	QRISK2 to determine 10-yr risk of non-fatal and fatal CVD events (CHD, CVA, PAD)	FRS or PCE to determine 10-yr risk of non-fatal and fatal CVD events
Step 1: Identify statin-benefit group	Statin benefit groups: (moderate to high-intensity statin) History of ASCVD; LDL-C ≥ 190, age ≥ 21; DM at age 40-75 with LDL-C ≥ 70; ≥ 7.5% of ASCVD risk at age 40-75 with LDL-C; ≥ 70 (in some individuals, not all; discussion required) Consider moderate intensity statin as initial dose for: DM with ≤ 7.5% ASCVD risk; ≥ 7.5% of ASCVD risk without DM Inadequate data to make recommendation (weigh risk, benefit and patient preference) DM at age < 40 or > 75 with LDL-C > 70; Age < 40 or > 75 with LDL-C > 70; 5%-7.4% of ASCVD risk at age 40-75 with LDL-C > 70; < 5% of ASCVD risk at age 40-75 with LDL-C > 70; Age < 40 with low 10 yr ASCVD risk but high lifetime risk based on 1 strong or multiple risk factors; Those with serious co-morbidities and increased ASCVD risk (e.g., HIV, rheumatologic or inflammatory diseases, or solid organ transplantation) Other factors for consideration: family history of premature CVD, hsCRP ≥ 2, elevated CAC, ABI < 0.9, LDL-C ≥ 160	Statin benefit groups: (initial dose: Atorvastatin 20 mg/d) Type 1 DM; CKD st. III; Risk score > 10%; Age > 85; Familial hypercholesterolemia Elevated risk groups that are underestimated by or not included in QRISK2: Possible benefit with statin HIV; Serious mental problem; On medication that cause dyslipidemia (antipsychotic, corticosteroid, immunosuppressant); Autoimmune disorder and systemic inflammatory disorder; TG > 175; On anti-hypertension or lipid modification therapy; Recently stopped smoking	Statin benefit group: (initial dose: Atorvastatin 10-20 mg/d) Risk score > 12% Moderate dose statin initiation can be considered in patient with 6%-12% risk score after discussion of benefit, risk, and patients’ preference
Step 2: Determine adequacy of treatment effect	For group treated with high intensity statin: > 50% ↓ of LDL-C For group treated with moderate intensity statin: 30%-50% ↓ of LDL-C If patients are already on statin and baseline LDL-C is unknown, an LDL-C < 100 was observed in most individuals receiving high-intensity statin therapy in RCTs	> 40% ↓ of non-HDL-C	No objective parameters recommended
Step 3: Follow-up lipids	1-3 mo after initiation therapy Every 3-12 mo as clinically indicated thereafter	3 mo after initiation of therapy Annually when target achieved	Not recommended Lipid measurement can be utilized for compliance monitoring
Step 4: Options if treatment effect judged not adequate	Reinforce lifestyle change and adherence to medication Exclude secondary cause of dyslipidemia Add non-statin agent in those with LDL-C ≥ 190 or DM at age 40-75 with LDL-C ≥ 70	Discuss adherence to lifestyle and medication Up-titrate statin dose; may go up to a torvastatin 80 mg/d	No recommendation

ACC/AHA: American College of Cardiology/American Heart Association; NICE: National Institute for Health and Care Excellence; PCE: Pooled Cohort Equations; ASCVD: Atherosclerotic cardiovascular disease; CHD: Coronary heart disease; CVA: Cerebrovascular accident; CVD: Cardiovascular disease; PAD: Peripheral artery disease; FRS: Framingham Risk Score; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; DM: Diabetes mellitus; CKD: Chronic kidney disease; HIV: Human immunodeficiency virus; TG: Triglyceride; hsCRP: High sensitivity C-reactive protein; ABI: Ankle-brachial index; RCT: Randomized controlled trials.

Table 2 Target-level strategies

Strategy	EAS/ESC 2011	CCS 2012	IAS 2013	NLA 2014	AACE 2012
Risk score	SCORE chart to estimate 10-yr risk of fatal CVD	Modified FRS to estimate 10-yr risk of non-fatal and fatal CVD	Lifetime FRS to estimate lifetime risk of non-fatal and fatal CVD	PCE or FRS or lifetime FRS	FRS to determine 10-yr risk of non-fatal and fatal CVD
Step 1: Stratify CVD risk	Very-high: ≥ 10% of fatal CVD risk; CHD equivalent risk; DM with microalbuminuria; CKD st. III High: 5%-9% of fatal CVD risk; DM; 1 markedly abnormal risk factor Moderate: 1%-4% of fatal CVD risk Low: < 1% of fatal CVD risk	High: ≥ 20% risk of CVD; CHD risk equivalent; DM, age > 40 or > 30 with 15 yr DM history; CKD st. IIIb or IIIa with microalbuminuria; HTN with ≥ 3 CVD risk factors Intermediate: 10%-19% risk of CVD Low: < 10% risk of CVD (CVD risk factor: age > 55, smoker, TC/HDL-C > 6, LVH, abnormal ECG, microalbuminuria)	High: ≥ 45% lifetime risk of CVD; DM with major risk factor; Familial hyperlipidemia; CKD Moderately-high: 30%-44% lifetime risk of CVD; DM alone; Metabolic syndrome; CKD Moderate: 15%-29% lifetime risk of CVD Low: < 15% lifetime risk of CVD [Major risk factor: high LDL-C, HDL-C < 40, HTN, smoker, family history of premature CAD, age (men > 55, women > 65)]	Very-high: CHD risk equivalent; DM with ≥ 2 major risk factors or evidence of end organ damage High: DM with 0-1 major risk factor; CKD st. IIIb; LDL-C ≥ 190; ≥ 3 major risk factors; ≥ 1 secondary risk (marked major CVD risk, LDL-C > 160 or non-HDL-C > 190, CAC > 300, hsCRP > 2, Lp(a) > 50, microalbuminuria); High risk score (PCE > 15%, FRS > 10%, lifetime FRS > 45%) Intermediate: 2 major risk factors Low: 0-1 risk factor	Very-high: CHD risk equivalent + ≥ 1 major risk factor High: CAD risk equivalent; ≥ 2 major risk factor + ≥ 20% risk of CVD Moderately-high: ≥ 2 major risk factor + 10%-19% risk of CVD Moderate: ≥ 2 major risk factor + < 10% risk of CVD Low: ≥ 1 major risk factor
Step 2: Determine target	Very-high: LDL-C < 70; Alt: ApoB < 80, non-HDL-C < 100 High: LDL-C < 100; Alt: ApoB < 80, non-HDL-C < 130 Moderate-Low: LDL-C < 100-115	High: LDL-C < 77 or ≥ 50% ↓; Alt: ApoB < 80, Non-HDL-C < 100 Intermediate: LDL-C < 77 or ≥ 50% ↓ Alt: ApoB < 80, Non-HDL-C < 100 Low : ≥ 50% ↓ of LDL-C	High to moderately-high: LDL-C < 100 or non-HDL-C < 130 (goal may be lower for very-high risk) Moderate to low: LDL-C < 130 or non-HDL-C < 160	Very-high: LDL-C < 70, non-HDL-C < 100 Alt: ApoB < 80 High-Moderate-Low: LDL-C < 100, non-HDL-C < 130	Very-high: LDL-C < 70, ApoB < 80 High: LDL-C < 100, ApoB < 90 Moderately-high: LDL-C < 130 Moderate: LDL-C < 130; Low: LDL-C < 160; All category: HDL-C > 40, TG < 150
Step 3: Treat according to risk	Very-high or High: Lifestyle intervention + drug intervention Moderate: Lifestyle inter-vention; consider drug if uncontrolled with lifestyle Low: Life style intervention only	High: Statin and lifestyle change Intermediate: LDL-C > 135: Statin if lifestyle change insufficient; LDL-C < 135: Get ApoB or non-HDL-C: # Apo B > 120 or Non-HDL-C > 165: Start statin if lifestyle change insufficient # Apo B< 120 or Non-HDL-C < 165: Lifestyle change Optional use of secondary test for further stratification Low: LDL-C > 190: Lifestyle change and statin; 5%-9% risk of CVD: Lifestyle change only optional use of secondary test for further stratification; < 5% risk of CVD: Lifestyle change only	High: Statin and lifestyle change Moderately-high: Lifestyle change; Initiation of statin may be considered Moderate: Lifestyle change; initiation of statin may be considered if LDL-C > 160 Low: Lifestyle change only	Very-high: Statin and lifestyle change; statin optional if baseline LDL-C, non-HDL-C and ApoB below target High: Concurrent statin and lifestyle change or statin after insufficient lifestyle change Moderate: Lifestyle change only; statin may be considered after 3 mo of optimal lifestyle change and LDL-C > 130 Low: Lifestyle change only; statin may be considered after 3 mo of optimal lifestyle change and LDL-C > 160	Exclude secondary cause of hyperlipidemia; Lifestyle change; Lipid lowering agent; Combination lipid lowering agent
Step 4: Follow-up lipids	1-12 wk after initiation; 1-3 mo after every change of dose or change of medication; Annually when target is achieved			Every 3 mo until target is achieved; Every 4-12 mo when target is achieved	6 wk after initiation; Every 6-12 mo when target is achieved
Step 5: Options if target not reached	Up-titration of statin dose; Add non-statin agent			Add non-statin agent; Referral to lipid specialist

ESC: European Society of Cardiology; EAS: European Atherosclerosis Society; CCS: Canadian Cardiovascular Society; IAS: International Atherosclerosis Society; NLA: National Lipid Association; AACE: American Association of Clinical Endocrinologists; FRS: Framingham risk score; PCE: Pooled Cohort Equations; CVD: Cardiovascular disease; CHD: Coronary heart disease; CKD: Chronic kidney disease; DM: Diabetes mellitus; CAD: Coronary artery disease; LDL-C: Low density lipoprotein cholesterol; HDL-C: High density lipoprotein cholesterol; hsCRP: High sensitivity C-reactive protein; TG: Triglyceride; ApoB: Apolipoprotein B.