Review question
What is the effect of various doses of fluvastatin on blood lipids?
The effects of various doses of fluvastatin on blood lipids were quantified in 145 studies.
Background
Fluvastatin is thought to be the least potent statin but the precise dose-related effect of fluvastatin on lipids is unknown. It would be interesting to know how much fluvastatin lowers blood lipids in the 145 studies retrieved.
Search date
The evidence is current to February 2017.
Study characteristics
Randomised placebo-controlled and uncontrolled before and after trials of different fixed doses of fluvastatin. The studies were of three to 12 weeks duration.
Participants could be of any age and gender with or without evidence of cardiovascular disease.
One-hundred and forty-five included trials involved 18,846 participants.
Key results
Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%. There were 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 fluvastatin on blood HDL cholesterol.
Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin.
Of the 36 placebo-controlled trials only 16 reported withdrawals due to adverse effects (WDAEs). WDAEs were higher, risk ratio 1.52 (95% confidence interval (CI) 0.94 to 2.45), demonstrating uncertainty, but the possibility of an increase in adverse effects.
Quality of the evidence
The quality of evidence was high for the lipid levels. For WDAEs the quality of evidence was very low because 20 (55.6%) out of 36 placebo-controlled trials did not report WDAEs.
Fluvastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, fluvastatin is 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin. This review did not provide a good estimate of the incidence of harms associated with fluvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 56% of the placebo-controlled trials.
Fluvastatin is thought to be the least potent statin on the market, however, the dose-related magnitude of effect of fluvastatin on blood lipids is not known.
Primary objective
To quantify the effects of various doses of fluvastatin on blood total cholesterol, low-density lipoprotein (LDL cholesterol), high-density lipoprotein (HDL cholesterol), and triglycerides in participants with and without evidence of cardiovascular disease.
Secondary objectives
To quantify the variability of the effect of various doses of fluvastatin.
To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials.
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to February Week 2 2017), MEDLINE In-Process, MEDLINE Epub Ahead of Print, Embase (1974 to February Week 2 2017), the World Health Organization International Clinical Trials Registry Platform, CDSR, DARE, Epistemonikos and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. No language restrictions were applied.
Randomised placebo-controlled and uncontrolled before and after trials evaluating the dose response of different fixed doses of fluvastatin 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 data from placebo-controlled and uncontrolled before and after trials into Review Manager 5 as continuous and generic inverse variance data, respectively. WDAEs information was collected from the placebo-controlled trials. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.
One-hundred and forty-five trials (36 placebo controlled and 109 before and after) evaluated the dose-related efficacy of fluvastatin in 18,846 participants. The participants were of any age with and without evidence of cardiovascular disease, and fluvastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 2.5 mg to 80 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 fluvastatin on blood HDL cholesterol. Fluvastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 15% to 33%, total cholesterol by 11% to 25% and triglycerides by 3% to 17.5%. For every two-fold dose increase there was a 6.0% (95% CI 5.4 to 6.6) decrease in blood LDL cholesterol, a 4.2% (95% CI 3.7 to 4.8) decrease in blood total cholesterol and a 4.2% (95% CI 2.0 to 6.3) decrease in blood triglycerides. The quality of evidence for these effects was judged to be high. When compared to atorvastatin and rosuvastatin, fluvastatin was about 12-fold less potent than atorvastatin and 46-fold less potent than rosuvastatin at reducing LDL cholesterol. Very low quality of evidence showed no difference in WDAEs between fluvastatin and placebo in 16 of 36 of these short-term trials (risk ratio 1.52 (95% CI 0.94 to 2.45).