Sarpreet S Sekhon's research while affiliated with University of British Columbia and other places

Background: 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. Objectives: Primary objectiveTo 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 objectivesTo quantify the variability of the effect of various doses of fluvastatin.To quantify withdrawals due to adverse effects (WDAEs) in randomised placebo-controlled trials. Search methods: 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 We also contacted authors of relevant papers regarding further published and unpublished work.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. Selection criteria: 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. Data collection and analysis: 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. Main results: 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). Authors' conclusions: 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.

This is the protocol for a review and there is no abstract. The objectives are as follows: Primary objective:: The objective of this review is to learn more about the pharmacology of fluvastatin by characterizing the dose-related effect and variability of the effect of fluvastatin on the surrogate markers: total cholesterol, low density lipoprotein (LDL cholesterol), high density lipoprotein (HDL cholesterol), and triglycerides. We will aim to quantify the effects of various doses of fluvastatin on serum total cholesterol, LDL cholesterol, triglycerides and HDL cholesterol in people with and without evidence of cardiovascular disease. The effects of statins on morbidity and mortality, however, is not the objective of this systematic review. Secondary objective:: To quantify the variability of the effect of various doses of fluvastatin on withdrawals due to adverse effects.

Rosuvastatin is one of the most potent statins and is currently widely prescribed. It is therefore important to know the dose-related magnitude of effect of rosuvastatin on blood lipids. Primary objectiveTo quantify the effects of various doses of rosuvastatin on serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, non-HDL-cholesterol and triglycerides in participants with and without evidence of cardiovascular disease. Secondary objectivesTo quantify the variability of the effect of various doses of rosuvastatin.To quantify withdrawals due to adverse effects (WDAEs) in the randomized placebo-controlled trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 10 of 12, 2014 in The Cochrane Library, MEDLINE (1946 to October week 5 2014), EMBASE (1980 to 2014 week 44), Web of Science Core Collection (1970 to 5 November 2014) and BIOSIS Citation Index (1969 to 31 October 2014). No language restrictions were applied. Randomized controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of rosuvastatin on blood lipids over a duration of three to 12 weeks. Two review authors independently assessed eligibility criteria for studies to be included and extracted data. WDAEs information was collected from the placebo-controlled trials. One-hundred and eight trials (18 placebo-controlled and 90 before-and-after) evaluated the dose-related efficacy of rosuvastatin in 19,596 participants. Rosuvastatin 10 to 40 mg/day caused LDL-cholesterol decreases of 46% to 55%, when all the trials were combined using the generic inverse variance method. The quality of evidence for these effects is high. Log dose-response data over doses of 1 to 80 mg, revealed strong linear dose-related effects on blood total cholesterol, LDL-cholesterol and non-HDL-cholesterol. When compared to atorvastatin, rosuvastatin was about three-fold more potent at reducing LDL-cholesterol. There was no dose-related effect of rosuvastatin on blood HDL-cholesterol, but overall, rosuvastatin increased HDL by 7%. There is a high risk of bias for the trials in this review, which would affect WDAEs, but unlikely to affect the lipid measurements. WDAEs were not statistically different between rosuvastatin and placebo in 10 of 18 of these short-term trials (risk ratio 0.84; 95% confidence interval 0.48 to 1.47). The total blood total cholesterol, LDL-cholesterol and non-HDL-cholesterol-lowering effect of rosuvastatin was linearly dependent on dose. Rosuvastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with atorvastatin, this represents a three-fold greater potency. This review did not provide a good estimate of the incidence of harms associated with rosuvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 44% of the placebo-controlled trials.