Key messages
• Pravastatin decreases low-density lipoprotein cholesterol and the effect is dependent on the dose over the range of 5 mg to 160 mg.
• Pravastatin at 80 mg/day is the maximal licensed dose.
• From other systematic reviews we conducted, pravastatin has a similar effect on cholesterol to fluvastatin and has a lesser effect on cholesterol than the other statins.
What are cholesterol and blood fats?
Cholesterol is required to build and maintain all animal cell membranes and is critical to human life. Main components of cholesterol are low-density lipoprotein, high-density lipoprotein, and triglycerides. Low-density lipoprotein transports fat molecules around the body in the blood and delivers fat molecules to cells. High-density lipoprotein removes fat molecules from cells and transports it to the liver. Cholesterol and its components low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol can be measured in the blood. Triglycerides are found in all lipoproteins and can also be measured in the blood. Blood fats are thought to be related to adverse events affecting the heart and blood vessels.
What is pravastatin?
Pravastatin is one of a class of medication called statins that lower blood cholesterol. What are other statins? Do they have any unwanted effects?
What did we want to find out?
How do different doses of pravastatin affect fats in our blood?
What did we do?
We searched for studies that compared pravastatin with a non-active form of treatment (placebo) over a three to 12-week duration and measured cholesterol and other fats in the blood. We assessed unwanted effects by looking at how many people left the studies because of unwanted effects. We considered people of any age, with and without evidence of cardiovascular disease.
What did we find?
We found 64 trials that studied the effects of different doses of pravastatin in 9771 participants.
Main results
People taking 5 mg to 160 mg of pravastatin per day lowered their low-density lipoprotein cholesterol by 18.3% to 35.3%.
The difference in unwanted effects between pravastatin and placebo was uncertain in these short-term studies.
What are the main limitations of the evidence?
Many studies did not report unwanted effects nor the number of people who left the studies because of unwanted effects.
How up to date is the evidence?
The evidence is up-to-date to September 2021.
Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.
A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.
Primary objective
To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review.
Secondary objectives
• To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides.
• To assess the effect of pravastatin on withdrawals due to adverse effects.
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
Randomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
Sixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.