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Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years
L A Simons1, P J Nestel, P Clifton
1Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW.
Insights
Pravastatin effectively lowers LDL cholesterol and is safe for long-term use in hyperlipidemia patients. This study found significant reductions in cholesterol with pravastatin over three years.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Lipidology
Background:
- Hypercholesterolemia and combined hyperlipidemia are significant risk factors for cardiovascular disease.
- Dietary interventions are the first line of treatment, but often require pharmacological support.
- Statins, such as pravastatin, are a cornerstone of lipid-lowering therapy.
Purpose of the Study:
- To evaluate the efficacy, safety, and tolerability of pravastatin in managing hyperlipidemia over a three-year period.
- To compare pravastatin with cholestyramine in lipid-lowering effects.
- To assess the long-term effects of pravastatin on lipid profiles.
Main Methods:
- An open, multicenter randomized study involving patients with primary or combined hyperlipidemia.
- Patients were assigned to pravastatin (20 mg/day or 40 mg/day) or cholestyramine (16 g/day) for 12 weeks, with subsequent dose titration and combination therapy allowed.
- Lipid levels, lipoproteins, and safety parameters were monitored regularly, with adverse events systematically recorded.
Main Results:
- All treatments significantly reduced total and LDL cholesterol within 12 weeks (P < 0.001).
- Pravastatin demonstrated sustained LDL cholesterol reduction over 36 months, with higher doses showing greater efficacy.
- HDL cholesterol increased across all treatment groups, while triglyceride levels decreased with high-dose pravastatin but increased with cholestyramine.
Conclusions:
- Pravastatin is an effective, safe, and well-tolerated drug for lowering lipids.
- Combination therapy with pravastatin achieved greater LDL reduction, maintained over three years.
- Long-term pravastatin treatment offers significant benefits for patients with hyperlipidemia.
Objective:
To assess the efficacy, safety and tolerability of pravastatin over three years of treatment.
Design:
An open, multicentre randomised study.
Setting:
Subjects receiving tertiary care at three hospital lipid clinics.
Patients:
Subjects with primary hypercholesterolaemia (type IIa) or combined hyperlipidaemia (type IIb), already stabilised on a cholesterol-lowering diet, with low density lipoprotein (LDL) cholesterol levels of greater than 4.7 mmol/L and triglyceride levels of less than 4.5 mmol/L. Sixty-one subjects were randomly assigned to the treatment groups: 60 completed 12 weeks and 46 completed 30-36 months of treatment.
Interventions:
Subjects were randomly assigned to receive either pravastatin 20 mg/day, pravastatin 40 mg/day or cholestyramine 16 g/day for a period of 12 weeks. Subsequently, dose titration of pravastatin up to 40 mg/day was permitted, if required, and all groups received supplementary therapy with other lipid-lowering drugs.
Main Outcome Measures:
Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored.
Results:
There were significant reductions in total and LDL cholesterol levels with all treatments over 12 weeks (P < 0.001). The mean reductions (+/- SD) in LDL cholesterol were 26% +/- 14% in the group taking pravastatin 20 mg/day (n = 21), 30% +/- 8% in the group taking pravastatin 40 mg/day (n = 21) and 34% +/- 13% in the group taking resin (n = 18). The percentage changes in LDL cholesterol were independent of age, baseline cholesterol level or lipid phenotype. High density lipoprotein (HDL) cholesterol levels were significantly increased, by 8%-18% with all treatments (P < 0.001). Triglyceride levels were reduced by high-dose pravastatin only (7% +/- 29%), but were found to increase with resin (45% +/- 63%). During long-term treatment over 36 months, still greater reductions in total and LDL cholesterol were found in patients taking pravastatin (n = 35), but not in those taking resin (n = 11). There was an apparent decrease in effect beyond 18 months in both groups, possibly related to reduced compliance with diet or cholestyramine intake. Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events). Adverse events during 12 weeks' monotherapy with pravastatin included central nervous system (CNS) symptoms (12%), gastrointestinal (GIT) symptoms (7%) and an acute hepatitic reaction (one subject). Of those in the resin therapy group, 22% developed GIT symptoms. Myalgia occurred in three subjects using a combination of pravastatin and clofibrate, but this resolved fully upon clofibrate withdrawal.
Conclusions:
Pravastatin was found to be a relatively effective, safe and well tolerated lipid-lowering drug. Still greater LDL reduction was achieved with pravastatin combination therapy and this was essentially maintained over three years.