# Statin Therapy -- ACC/AHA 2018

## Statin Intensity Definitions

Statin therapy is classified by the expected percentage reduction in LDL-C, not by specific LDL-C targets (Class I, Level of Evidence A):

### High-Intensity Statin Therapy (LDL-C Reduction >= 50%)

| Drug | Daily Dose | Route | Frequency |
|---|---|---|---|
| **Atorvastatin** | 40--80 mg | Oral | Once daily |
| **Rosuvastatin** | 20--40 mg | Oral | Once daily |

### Moderate-Intensity Statin Therapy (LDL-C Reduction 30--49%)

| Drug | Daily Dose | Route | Frequency |
|---|---|---|---|
| **Atorvastatin** | 10--20 mg | Oral | Once daily |
| **Rosuvastatin** | 5--10 mg | Oral | Once daily |
| **Simvastatin** | 20--40 mg | Oral | Once daily (evening) |
| **Pravastatin** | 40--80 mg | Oral | Once daily |
| **Lovastatin** | 40--80 mg | Oral | Once daily (evening with food) |
| **Fluvastatin XL** | 80 mg | Oral | Once daily |
| **Fluvastatin** | 40 mg | Oral | Twice daily |
| **Pitavastatin** | 1--4 mg | Oral | Once daily |

### Low-Intensity Statin Therapy (LDL-C Reduction < 30%)

| Drug | Daily Dose | Route | Frequency |
|---|---|---|---|
| **Simvastatin** | 10 mg | Oral | Once daily (evening) |
| **Pravastatin** | 10--20 mg | Oral | Once daily |
| **Lovastatin** | 20 mg | Oral | Once daily (evening with food) |
| **Fluvastatin** | 20--40 mg | Oral | Once daily |

## Four Major Statin Benefit Groups

### Group 1: Clinical ASCVD (Secondary Prevention)

- **Definition:** History of acute coronary syndrome (ACS), myocardial infarction (MI), stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) of atherosclerotic origin.
- **Age <= 75 years:** High-intensity statin therapy to reduce LDL-C by >= 50% (Class I, Level of Evidence A).
- **Age > 75 years:** Clinician--patient discussion; it is reasonable to continue high-intensity statin therapy or initiate moderate-intensity statin therapy (Class IIa, Level of Evidence B-R).
- If high-intensity statin is not tolerated, use maximally tolerated statin (Class I, Level of Evidence A).

### Group 2: Severe Primary Hypercholesterolemia (LDL-C >= 190 mg/dL)

- **Age >= 20 years:** Maximally tolerated high-intensity statin therapy (Class I, Level of Evidence B-R).
- No 10-year ASCVD risk calculation is required; statin is indicated regardless of risk score.
- If LDL-C remains >= 100 mg/dL on maximally tolerated statin, adding ezetimibe is reasonable (Class IIa, Level of Evidence B-R).
- If LDL-C remains >= 100 mg/dL on statin + ezetimibe with multiple factors increasing subsequent ASCVD event risk, a PCSK9 inhibitor may be considered (Class IIb, Level of Evidence B-R).

### Group 3: Diabetes Mellitus (Ages 40--75)

- **All patients with diabetes, LDL-C >= 70 mg/dL:** Moderate-intensity statin therapy without 10-year ASCVD risk calculation (Class I, Level of Evidence A).
- **Higher-risk diabetes patients (ages 50--75 with multiple risk factors):** High-intensity statin to reduce LDL-C by >= 50% is reasonable (Class IIa, Level of Evidence B-R).
- **Diabetes ages 20--39:** Consider moderate-intensity statin if long-standing diabetes (>= 10 years for type 2 DM; >= 20 years for type 1 DM) or presence of albuminuria >= 30 mcg/mg creatinine, eGFR < 60 mL/min/1.73 m2, retinopathy, neuropathy, or ABI < 0.9 (Class IIa, Level of Evidence B-NR).

### Group 4: Primary Prevention (Ages 40--75, No ASCVD, No Diabetes)

- Calculate 10-year ASCVD risk using the Pooled Cohort Equations.
- **LDL-C 70--189 mg/dL and 10-year ASCVD risk >= 7.5%:** Moderate-intensity statin is reasonable after clinician--patient risk discussion (Class IIa, Level of Evidence A).
- **10-year ASCVD risk >= 20%:** High-intensity statin to reduce LDL-C by >= 50% (Class I, Level of Evidence A).
- **10-year ASCVD risk 5% to < 7.5%:** Consider moderate-intensity statin if risk-enhancing factors are present (Class IIb, Level of Evidence B-NR).
- **10-year ASCVD risk < 5%:** Lifestyle modifications only; statin generally not indicated.

## Treatment Decision Algorithm (Primary Prevention, Ages 40--75)

1. Assess lifestyle habits; encourage heart-healthy lifestyle across the lifespan.
2. If LDL-C >= 190 mg/dL --> Group 2: Maximally tolerated high-intensity statin (no risk calculation needed).
3. If diabetes mellitus present --> Group 3: Moderate-intensity statin (no risk calculation needed); consider high-intensity if multiple risk factors.
4. Calculate 10-year ASCVD risk using Pooled Cohort Equations.
   - If 10-year risk >= 20%: High-intensity statin (reduce LDL-C >= 50%).
   - If 10-year risk 7.5% to < 20%: Clinician--patient risk discussion; assess risk-enhancing factors. If decision uncertain, consider CAC scoring.
     - CAC = 0: May defer statin; reassess in 5--10 years.
     - CAC 1--99: Favors statin, especially if age >= 55.
     - CAC >= 100: Initiate statin therapy.
   - If 10-year risk 5% to < 7.5%: Consider statin if risk-enhancing factors present.
   - If 10-year risk < 5%: Lifestyle modifications only.

## Monitoring and Follow-Up

- Obtain fasting lipid panel 4 to 12 weeks after statin initiation or dose adjustment (Class I, Level of Evidence A).
- Repeat lipid panel every 3 to 12 months as needed to assess adherence and response (Class I, Level of Evidence A).
- Define response by percentage LDL-C reduction compared with baseline, not by a specific LDL-C target.
- If expected LDL-C percentage reduction is not achieved, assess adherence, lifestyle factors, and secondary causes before intensifying therapy.
- Measure baseline ALT before starting statin; routine hepatic function monitoring is NOT recommended unless clinically indicated (Class III: No Benefit, Level of Evidence B-R).
- Routine creatine kinase (CK) measurement is NOT recommended unless symptoms of myopathy develop (Class III: No Benefit, Level of Evidence B-R).

## Statin-Associated Side Effects

### Statin-Associated Muscle Symptoms (SAMS)
- Reported incidence: 1--5% in RCTs; 5--10% in clinical practice.
- Management: If intolerable muscle symptoms occur, discontinue the statin and allow symptoms to resolve. Then rechallenge with the same statin at a lower dose or an alternative statin (Class IIa, Level of Evidence B-NR).
- If symptoms recur with multiple statins, consider very low-dose statin combined with nonstatin therapy (ezetimibe).

### Statin-Associated New-Onset Diabetes
- Statins modestly increase risk of incident diabetes mellitus in susceptible individuals (those with metabolic syndrome, elevated BMI, elevated fasting glucose, or elevated HbA1c).
- This should NOT be cause for statin discontinuation; the cardiovascular benefit outweighs the diabetes risk.

### Rare but Serious Adverse Effects
- Rhabdomyolysis: very rare (< 0.1%); risk increased with drug interactions (e.g., cyclosporine, gemfibrozil, some macrolides, azole antifungals).
- Autoimmune myopathy: extremely rare; characterized by persistent CK elevation and proximal weakness even after statin discontinuation.

## Special Populations

### Adults > 75 Years
- RCT evidence for initiating statin therapy in adults > 75 years is limited.
- For those already on statin therapy, it is reasonable to continue (Class IIa, Level of Evidence B-R).
- Clinician--patient risk discussion considering comorbidities, life expectancy, polypharmacy, and patient preferences is recommended.

### Children and Adolescents
- Universal lipid screening is recommended once between ages 9--11 years and again between ages 17--21 years (Class IIa, Level of Evidence B-NR).
- Abnormal childhood LDL-C: >= 130 mg/dL (>= 3.4 mmol/L).
- Drug therapy is reserved for children with severe hypercholesterolemia or familial hypercholesterolemia after intensive lifestyle intervention.

### Pregnancy and Breastfeeding
- Statins are contraindicated in pregnancy (Class III: Harm, Level of Evidence C-EO).
- Discontinue statins 1--2 months before planned conception; resume postpartum.
