Review question
How do different doses of pitavastatin affect fats in our blood?
Background
Pitavastatin is the newest statin on the market. We don't know the effect of different sizes of dose on the amount of fats in our blood.
Search date
We looked at research up to March 2019.
Study characteristics
We looked for high-quality randomised trials (RCTs) and before-and-after studies with pitavastatin in different dose sizes . The trials were between three and 12 weeks long.
Participants in the trials could be of any age and gender, with or without cardiovascular disease.
Key results
People taking 1 mg to 16 mg of pitavastatin per day lowered their LDL cholesterol by 33.3% to 54.7%. The higher the dose, the lower the levels of three measures of cholesterol. The average increase in HDL cholesterol for all doses was 4%.
For lowering LDL cholesterol, pitavastatin is 6-times stronger than atorvastatin, 1.7-times stronger than rosuvastatin, 77-times stronger than fluvastatin and 3.3-times weaker than cerivastatin.
In the RCTS, no person out of 109 in the placebo group and three out of 262 people in the pitavastatin group dropped out due to adverse effects.
Certainty of the evidence
There is a high level of trust around the effects of pitavastatin on total cholesterol, LDL cholesterol and triglycerides.
Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.
Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.
Primary objective
To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease.
To compare the effect of pitavastatin on surrogate markers with other statins.
Secondary objectives
To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects.
The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization 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.
RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.
Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.