What is Pravastatin?
Pravastatin is an HMG-CoA reductase inhibitor (statin) approved by the FDA to reduce cardiovascular risk and lower LDL cholesterol in adults and children with hyperlipidemia. 1
Mechanism of Action
Pravastatin works by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. 2 This mechanism:
- Reduces hepatic cholesterol synthesis 2
- Increases expression of hepatic LDL receptors 2
- Reduces hepatic VLDL synthesis 2
Unlike lovastatin and simvastatin, pravastatin is active in its parent form and does not require metabolic conversion. 2
FDA-Approved Indications
Pravastatin is indicated for: 1
- Primary prevention: Reducing risk of myocardial infarction, revascularization procedures, and cardiovascular mortality in adults with elevated LDL-C without clinically evident coronary heart disease
- Secondary prevention: Reducing coronary death, myocardial infarction, revascularization, stroke/TIA, and slowing coronary atherosclerosis progression in adults with established CHD
- Hyperlipidemia treatment: As adjunct to diet for reducing LDL-C in adults with primary hyperlipidemia
- Pediatric use: Reducing LDL-C in children aged 8 years and older with heterozygous familial hypercholesterolemia
- Specialized dyslipidemia: Treating primary dysbetalipoproteinemia and hypertriglyceridemia in adults
Dosing and Intensity Classification
Standard Dosing
The recommended starting dosage for adults is 40 mg to 80 mg once daily, taken at any time of day with or without food. 1
For pediatric patients: 1
- Ages 8-13 years: 20 mg once daily
- Ages 14-18 years: 40 mg once daily (starting dose)
Statin Intensity Classification
According to the 2018 AHA/ACC guidelines, pravastatin is classified as: 3
- Moderate-intensity: Pravastatin 40 mg (80 mg) - lowers LDL-C by 30-49%
- Low-intensity: Pravastatin 10-20 mg - lowers LDL-C by <30%
Pravastatin does not achieve high-intensity statin therapy (≥50% LDL-C reduction) at any dose. 3 For patients requiring high-intensity therapy or unable to achieve LDL-C goals on pravastatin 80 mg daily, alternative LDL-C-lowering treatment should be prescribed. 1
Clinical Efficacy
Lipid-Lowering Effects
Pravastatin demonstrates dose-proportional LDL-C reduction: 4
- 10 mg/day: 18% LDL-C reduction
- 20 mg/day: 23% LDL-C reduction
- 40 mg/day: 31% LDL-C reduction
Total cholesterol reductions range from 20-23% at doses of 10-20 mg twice daily. 5 Pravastatin also increases HDL-C by 2-20% and reduces triglycerides, though these effects are not dose-dependent. 4
Cardiovascular Outcomes
Pravastatin 40 mg daily has been extensively studied in randomized controlled trials and consistently demonstrates a 24% reduction in cardiovascular death. 6 Major trials supporting its efficacy include: 3
- Secondary prevention: The Scandinavian Simvastatin Survival Study (4S) subgroup showed a 50% relative risk reduction for cardiovascular events in patients with diabetes (absolute risk reduction 23%). 3
- Primary prevention: Multiple trials demonstrated cardiovascular risk reduction, though the PROSPER trial showed a trend toward harm in elderly diabetic patients (relative risk 1.23). 3
Safety Profile
Common Adverse Effects
Pravastatin is generally well tolerated with minimal adverse effects. 7 The most common adverse events include: 1, 7
- Gastrointestinal events
- Renal or genitourinary symptoms
- Respiratory disorders
- Headaches
- Musculoskeletal pain
Serious Warnings
Myopathy and rhabdomyolysis are the most serious risks. 1 Risk factors include:
- Age ≥65 years 1
- Uncontrolled hypothyroidism 1
- Renal impairment 1
- Concomitant use with certain drugs 1
- Higher pravastatin dosage 1
Discontinue pravastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. 1 Patients should be instructed to report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. 1
Immune-mediated necrotizing myopathy (IMNM), a rare autoimmune myopathy, has been reported and requires discontinuation if suspected. 1
Hepatic dysfunction: Increases in serum transaminases and rare reports of fatal/non-fatal hepatic failure have occurred. 1 Pravastatin is contraindicated in acute liver failure or decompensated cirrhosis. 1
Special Populations
Renal Impairment
For severe renal impairment, the recommended starting dose is 10 mg once daily, with a maximum dose of 40 mg once daily. 1
Pregnancy Considerations
The 2022 ACC Expert Consensus indicates that pravastatin's safety profile is being studied for prevention of pre-eclampsia in high-risk pregnant women. 3 Recent large observational studies have not demonstrated evidence of harm to mother or fetus with statin use, though the FDA previously contraindicated statins in pregnancy. 3 For very high-risk pregnant patients (including those with homozygous familial hypercholesterolemia or clinical ASCVD), individual benefit-risk discussions are appropriate. 3
Elderly Patients
Pravastatin 40 mg/day effectively reduces coronary events in elderly patients (≥60 or ≥65 years) with or without hypercholesterolemia. 7 The drug is well tolerated in this population and should be considered first-line for primary or secondary prevention in older individuals with CHD or multiple CHD risk factors. 7
Clinical Positioning
When the expected 25-34% LDL-C lowering would be sufficient to reach an LDL-C goal of <2.5 mmol/L (<97 mg/dL), treatment should be started with pravastatin. 6 However, for patients requiring more aggressive LDL-C reduction (≥50%), high-intensity statins like atorvastatin 40-80 mg or rosuvastatin 20-40 mg are preferred. 3
Pravastatin's advantages include its extensive evidence base, proven cardiovascular outcomes reduction, favorable tolerability profile, and availability as a low-cost generic medication. 6