Cerivastatin for lowering lipids
Background Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose‐related magnitude of effect of cerivastatin on blood lipids is not known. Objectives Primary objective To quantify the effects of various d...
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| creator | Adams, Stephen P Tiellet, Nicholas Alaeiilkhchi, Nima Wright, James M Adams, Stephen P |
| description | Background
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose‐related magnitude of effect of cerivastatin on blood lipids is not known.
Objectives
Primary objective
To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease.
The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose‐related effect and variability of the effect of cerivastatin on surrogate markers.
Secondary objectives
To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
Search methods
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
Selection criteria
RCTs and controlled before‐and‐after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
Data collection and analysis
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before‐and‐after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. 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
Fifty trials (19 RCTs and 31 before‐and‐after studies) evaluated the dose‐related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any |
| doi_str_mv | 10.1002/14651858.CD012501.pub2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6984625</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2345504311</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4732-cfe16cca729b07be4766c5c87244eb2df6592716b64d1c1e20d12af3ff792a2e3</originalsourceid><addsrcrecordid>eNqFkMtOwzAURC0EoqXwC1WWbFJ8HT-SDRKEp1SJDawtx3FaozQudtqqf0-iPgRsWNnyzJ1zPQiNAU8AY3IDlDNIWTrJHzAQhmGyXBXkBA17Ie6V0x_3AboI4RPjhGdEnKNBAlkKVMAQRbnxdq1Cq1rbRJXzUe023VMzi2q7tGW4RGeVqoO52p8j9PH0-J6_xNO359f8bhprKhIS68oA11oJkhVYFIYKzjXTqSCUmoKUFWcdGnjBaQkaDMElEFUlVSUyoohJRuh2l9v9Y2FKbZrWq1ouvV0ov5VOWflbaexcztxa8iylnLAu4Hof4N3XyoRWLmzQpq5VY9wqSJJQxjBNADor31m1dyF4Ux0xgGVfrzzUKw_19nDSDY5_LnkcO_TZGe53ho2tzVZqp-e-4_-T-4fyDbW7ipQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2345504311</pqid></control><display><type>article</type><title>Cerivastatin for lowering lipids</title><source>MEDLINE</source><source>Cochrane Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Adams, Stephen P ; Tiellet, Nicholas ; Alaeiilkhchi, Nima ; Wright, James M ; Adams, Stephen P</creator><creatorcontrib>Adams, Stephen P ; Tiellet, Nicholas ; Alaeiilkhchi, Nima ; Wright, James M ; Adams, Stephen P</creatorcontrib><description>Background
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose‐related magnitude of effect of cerivastatin on blood lipids is not known.
Objectives
Primary objective
To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease.
The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose‐related effect and variability of the effect of cerivastatin on surrogate markers.
Secondary objectives
To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
Search methods
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
Selection criteria
RCTs and controlled before‐and‐after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
Data collection and analysis
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before‐and‐after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. 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
Fifty trials (19 RCTs and 31 before‐and‐after studies) evaluated the dose‐related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose‐response data over doses of 2.5 mg to 80 mg revealed strong linear dose‐related effects on LDL cholesterol, total cholesterol and triglycerides.
When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin at reducing LDL cholesterol; 233‐fold more potent than fluvastatin, 18‐fold more potent than atorvastatin and six‐fold more potent than rosuvastatin at reducing total cholesterol; and 125‐fold more potent than fluvastatin, 11‐fold more potent than atorvastatin and 13‐fold more potent than rosuvastatin at reducing triglycerides. There was no dose‐related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short‐term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).
Authors' conclusions
The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose‐response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin in reducing LDL cholesterol, and 233‐fold greater potency than fluvastatin, 18‐fold greater potency than atorvastatin and six‐fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.</description><identifier>ISSN: 1465-1858</identifier><identifier>ISSN: 1469-493X</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD012501.pub2</identifier><identifier>PMID: 31981471</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>A. Cardiovascular Disease: Primary Prevention ; A.1 Drugs ; A.1.2 Lipid Lowering ; Child health ; Cholesterol, HDL ; Cholesterol, HDL - blood ; Cholesterol, LDL ; Cholesterol, LDL - blood ; Dose-Response Relationship, Drug ; Drugs ; Heart & circulation ; Heart disease prevention ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Hydroxymethylglutaryl‐CoA Reductase Inhibitors ; Hyperlipidemias ; Hyperlipidemias - blood ; Hyperlipidemias - drug therapy ; Lipids ; Lipids - blood ; Medicine General & Introductory Medical Sciences ; Pharmacological Therapies ; Prevention ; Pyridines ; Pyridines - therapeutic use ; Randomized Controlled Trials as Topic ; Statins ; Treatment of essential Hypertension ; Treatment Outcome ; Triglycerides ; Triglycerides - blood</subject><ispartof>Cochrane database of systematic reviews, 2020-01, Vol.2020 (1), p.CD012501</ispartof><rights>Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4732-cfe16cca729b07be4766c5c87244eb2df6592716b64d1c1e20d12af3ff792a2e3</citedby><cites>FETCH-LOGICAL-c4732-cfe16cca729b07be4766c5c87244eb2df6592716b64d1c1e20d12af3ff792a2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31981471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adams, Stephen P</creatorcontrib><creatorcontrib>Tiellet, Nicholas</creatorcontrib><creatorcontrib>Alaeiilkhchi, Nima</creatorcontrib><creatorcontrib>Wright, James M</creatorcontrib><creatorcontrib>Adams, Stephen P</creatorcontrib><title>Cerivastatin for lowering lipids</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Background
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose‐related magnitude of effect of cerivastatin on blood lipids is not known.
Objectives
Primary objective
To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease.
The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose‐related effect and variability of the effect of cerivastatin on surrogate markers.
Secondary objectives
To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
Search methods
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
Selection criteria
RCTs and controlled before‐and‐after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
Data collection and analysis
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before‐and‐after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. 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
Fifty trials (19 RCTs and 31 before‐and‐after studies) evaluated the dose‐related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose‐response data over doses of 2.5 mg to 80 mg revealed strong linear dose‐related effects on LDL cholesterol, total cholesterol and triglycerides.
When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin at reducing LDL cholesterol; 233‐fold more potent than fluvastatin, 18‐fold more potent than atorvastatin and six‐fold more potent than rosuvastatin at reducing total cholesterol; and 125‐fold more potent than fluvastatin, 11‐fold more potent than atorvastatin and 13‐fold more potent than rosuvastatin at reducing triglycerides. There was no dose‐related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short‐term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).
Authors' conclusions
The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose‐response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin in reducing LDL cholesterol, and 233‐fold greater potency than fluvastatin, 18‐fold greater potency than atorvastatin and six‐fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.</description><subject>A. Cardiovascular Disease: Primary Prevention</subject><subject>A.1 Drugs</subject><subject>A.1.2 Lipid Lowering</subject><subject>Child health</subject><subject>Cholesterol, HDL</subject><subject>Cholesterol, HDL - blood</subject><subject>Cholesterol, LDL</subject><subject>Cholesterol, LDL - blood</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drugs</subject><subject>Heart & circulation</subject><subject>Heart disease prevention</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Hydroxymethylglutaryl‐CoA Reductase Inhibitors</subject><subject>Hyperlipidemias</subject><subject>Hyperlipidemias - blood</subject><subject>Hyperlipidemias - drug therapy</subject><subject>Lipids</subject><subject>Lipids - blood</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Pharmacological Therapies</subject><subject>Prevention</subject><subject>Pyridines</subject><subject>Pyridines - therapeutic use</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Statins</subject><subject>Treatment of essential Hypertension</subject><subject>Treatment Outcome</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><issn>1465-1858</issn><issn>1469-493X</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAURC0EoqXwC1WWbFJ8HT-SDRKEp1SJDawtx3FaozQudtqqf0-iPgRsWNnyzJ1zPQiNAU8AY3IDlDNIWTrJHzAQhmGyXBXkBA17Ie6V0x_3AboI4RPjhGdEnKNBAlkKVMAQRbnxdq1Cq1rbRJXzUe023VMzi2q7tGW4RGeVqoO52p8j9PH0-J6_xNO359f8bhprKhIS68oA11oJkhVYFIYKzjXTqSCUmoKUFWcdGnjBaQkaDMElEFUlVSUyoohJRuh2l9v9Y2FKbZrWq1ouvV0ov5VOWflbaexcztxa8iylnLAu4Hof4N3XyoRWLmzQpq5VY9wqSJJQxjBNADor31m1dyF4Ux0xgGVfrzzUKw_19nDSDY5_LnkcO_TZGe53ho2tzVZqp-e-4_-T-4fyDbW7ipQ</recordid><startdate>20200125</startdate><enddate>20200125</enddate><creator>Adams, Stephen P</creator><creator>Tiellet, Nicholas</creator><creator>Alaeiilkhchi, Nima</creator><creator>Wright, James M</creator><creator>Adams, Stephen P</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200125</creationdate><title>Cerivastatin for lowering lipids</title><author>Adams, Stephen P ; Tiellet, Nicholas ; Alaeiilkhchi, Nima ; Wright, James M ; Adams, Stephen P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4732-cfe16cca729b07be4766c5c87244eb2df6592716b64d1c1e20d12af3ff792a2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>A. Cardiovascular Disease: Primary Prevention</topic><topic>A.1 Drugs</topic><topic>A.1.2 Lipid Lowering</topic><topic>Child health</topic><topic>Cholesterol, HDL</topic><topic>Cholesterol, HDL - blood</topic><topic>Cholesterol, LDL</topic><topic>Cholesterol, LDL - blood</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drugs</topic><topic>Heart & circulation</topic><topic>Heart disease prevention</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Hydroxymethylglutaryl‐CoA Reductase Inhibitors</topic><topic>Hyperlipidemias</topic><topic>Hyperlipidemias - blood</topic><topic>Hyperlipidemias - drug therapy</topic><topic>Lipids</topic><topic>Lipids - blood</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Pharmacological Therapies</topic><topic>Prevention</topic><topic>Pyridines</topic><topic>Pyridines - therapeutic use</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Statins</topic><topic>Treatment of essential Hypertension</topic><topic>Treatment Outcome</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adams, Stephen P</creatorcontrib><creatorcontrib>Tiellet, Nicholas</creatorcontrib><creatorcontrib>Alaeiilkhchi, Nima</creatorcontrib><creatorcontrib>Wright, James M</creatorcontrib><creatorcontrib>Adams, Stephen P</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adams, Stephen P</au><au>Tiellet, Nicholas</au><au>Alaeiilkhchi, Nima</au><au>Wright, James M</au><au>Adams, Stephen P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerivastatin for lowering lipids</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2020-01-25</date><risdate>2020</risdate><volume>2020</volume><issue>1</issue><spage>CD012501</spage><pages>CD012501-</pages><issn>1465-1858</issn><issn>1469-493X</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><abstract>Background
Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose‐related magnitude of effect of cerivastatin on blood lipids is not known.
Objectives
Primary objective
To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease.
The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose‐related effect and variability of the effect of cerivastatin on surrogate markers.
Secondary objectives
To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.
Search methods
The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
Selection criteria
RCTs and controlled before‐and‐after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
Data collection and analysis
Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before‐and‐after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. 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
Fifty trials (19 RCTs and 31 before‐and‐after studies) evaluated the dose‐related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose‐response data over doses of 2.5 mg to 80 mg revealed strong linear dose‐related effects on LDL cholesterol, total cholesterol and triglycerides.
When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin at reducing LDL cholesterol; 233‐fold more potent than fluvastatin, 18‐fold more potent than atorvastatin and six‐fold more potent than rosuvastatin at reducing total cholesterol; and 125‐fold more potent than fluvastatin, 11‐fold more potent than atorvastatin and 13‐fold more potent than rosuvastatin at reducing triglycerides. There was no dose‐related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short‐term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74).
Authors' conclusions
The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose‐response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250‐fold more potent than fluvastatin, 20‐fold more potent than atorvastatin and 5.5‐fold more potent than rosuvastatin in reducing LDL cholesterol, and 233‐fold greater potency than fluvastatin, 18‐fold greater potency than atorvastatin and six‐fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>31981471</pmid><doi>10.1002/14651858.CD012501.pub2</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-1858 |
| ispartof | Cochrane database of systematic reviews, 2020-01, Vol.2020 (1), p.CD012501 |
| issn | 1465-1858 1469-493X 1465-1858 1469-493X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6984625 |
| source | MEDLINE; Cochrane Library; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | A. Cardiovascular Disease: Primary Prevention A.1 Drugs A.1.2 Lipid Lowering Child health Cholesterol, HDL Cholesterol, HDL - blood Cholesterol, LDL Cholesterol, LDL - blood Dose-Response Relationship, Drug Drugs Heart & circulation Heart disease prevention Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Hydroxymethylglutaryl‐CoA Reductase Inhibitors Hyperlipidemias Hyperlipidemias - blood Hyperlipidemias - drug therapy Lipids Lipids - blood Medicine General & Introductory Medical Sciences Pharmacological Therapies Prevention Pyridines Pyridines - therapeutic use Randomized Controlled Trials as Topic Statins Treatment of essential Hypertension Treatment Outcome Triglycerides Triglycerides - blood |
| title | Cerivastatin for lowering lipids |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T18%3A31%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cerivastatin%20for%20lowering%20lipids&rft.jtitle=Cochrane%20database%20of%20systematic%20reviews&rft.au=Adams,%20Stephen%20P&rft.date=2020-01-25&rft.volume=2020&rft.issue=1&rft.spage=CD012501&rft.pages=CD012501-&rft.issn=1465-1858&rft.eissn=1465-1858&rft_id=info:doi/10.1002/14651858.CD012501.pub2&rft_dat=%3Cproquest_pubme%3E2345504311%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2345504311&rft_id=info:pmid/31981471&rfr_iscdi=true |