Statins

What enzyme do statins inhibit?

HMG-CoA reductase

What is the effect of HMG-CoA reductase inhibition?

Prevents conversion of HMG-CoA to mevalonate (rate-limiting step in cholesterol synthesis)

Why are statin equivalent doses used?

To convert between statins for dose escalation, avoiding drug interactions, managing intolerance, or reducing cost

What are the statin equivalent doses?

Pitavastatin 2 mg = Rosuvastatin 5 mg = Atorvastatin 10 mg = Simvastatin 20 mg = Lovastatin 40 mg = Pravastatin 40 mg = Fluvastatin 80 mg

What are the contraindications to statins?

Breastfeeding, liver disease (including unexplained ↑ LFTs), and strong CYP3A4 inhibitors with simvastatin or lovastatin

What muscle-related adverse effects can statins cause?

Myalgia, myopathy, and rhabdomyolysis

What increases the risk of statin-induced muscle damage?

Higher statin doses, age >80 years, niacin, fibrates (especially gemfibrozil), uncontrolled hypothyroidism, and renal impairment

Can statins be used during pregnancy?

No, except continuation may be considered in patients at very high cardiovascular risk

How do statins affect blood glucose?

May increase A1C and fasting blood glucose, but benefits outweigh the risk in diabetes

What liver adverse effect can statins cause?

Hepatotoxicity with increased LFTs (rare)

When should LFTs be monitored with statin therapy?

At baseline and if symptoms of hepatotoxicity develop

When should CPK be checked during statin therapy?

If severe muscle symptoms occur

When should SCr/BUN be checked during statin therapy?

If decreased urine output occurs

When should simvastatin be taken?

In the evening

Which statins must be taken in the evening?

Lovastatin immediate-release and simvastatin

When should most statins be taken?

Once daily and at any time of day

Which statins require lower starting doses when CrCl <30 mL/min?

Lovastatin, pravastatin, rosuvastatin, and simvastatin

Which statin requires a lower starting dose when eGFR <60 mL/min/1.73 m²?

Pitavastatin

How do statins affect lipid levels?

↓ LDL 20-55%, ↑ HDL 5-15%, ↓ TG 10-30%

Which statins are CYP3A4 substrates?

Atorvastatin, lovastatin, and simvastatin

Which statins have fewer drug interactions?

Rosuvastatin and pravastatin

Which fibrate should NOT be combined with statins?

Gemfibrozil

How does amlodipine interact with statins?

Increases atorvastatin, lovastatin, and simvastatin concentrations

What is the maximum simvastatin dose with amlodipine?

20 mg/day

What is the maximum lovastatin dose with amlodipine?

20 mg/day

What drugs should NOT be used with simvastatin or lovastatin?

Grapefruit, protease inhibitors, azole antifungals, cyclosporine, cobicistat, and macrolides (except azithromycin)

What is the maximum simvastatin dose with amiodarone?

20 mg/day

What is the maximum lovastatin dose with amiodarone?

40 mg/day

What is the maximum simvastatin dose with non-DHP CCBs?

10 mg/day

What is the maximum lovastatin dose with non-DHP CCBs?

20 mg/day

What are statin-associated muscle symptoms (SAMS)?

The most common adverse effect of statins causing muscle damage

What are the typical symptoms of SAMS?

Symmetrical muscle soreness, tiredness, or weakness in large muscle groups (legs, back, arms)

When do statin-associated muscle symptoms usually occur?

Within 6 weeks of starting therapy, but they can occur at any time

What is myalgia?

Muscle soreness and tenderness

What is myopathy?

Muscle weakness with elevated CPK

What is rhabdomyolysis?

Muscle symptoms with CPK >10,000 IU/L plus myoglobinuria, which can cause acute renal failure

How can the risk of statin-associated muscle symptoms be reduced?

Avoid drug interactions (especially gemfibrozil + statin) and do not use simvastatin 80 mg/day

What should be done first if muscle symptoms occur during statin therapy?

Hold the statin

What laboratory test should be obtained if statin muscle symptoms are severe?

CPK

When should patients be reassessed after stopping a statin for muscle symptoms?

In 2-4 weeks

If muscle symptoms resolve, how should statin therapy be restarted?

Same statin at a lower dose, an alternate statin at an equivalent or lower dose, or modified dosing (e.g., every other day)

Which statins are preferred for modified (every-other-day) dosing?

Long half-life statins (atorvastatin or rosuvastatin)

What should be done if muscle symptoms return after a statin rechallenge?

Try a different statin at the lowest approved dose

When should nonstatin therapy be considered for statin intolerance?

After failure of at least 2 statin trials (including one at the lowest approved dose)

When can patients with rhabdomyolysis be started on nonstatin therapy?

Without attempting a statin rechallenge