Stephen P Adams1, Michael Tsang, James M Wright. 1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.stevenad@interchange.ubc.ca.
Abstract
BACKGROUND: Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids. OBJECTIVES: To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied. SELECTION CRITERIA: Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials. MAIN RESULTS: Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45). AUTHORS' CONCLUSIONS: Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
BACKGROUND:Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids. OBJECTIVES: To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied. SELECTION CRITERIA: Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials. MAIN RESULTS: Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45). AUTHORS' CONCLUSIONS: Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
Authors: Kevin Fitzgerald; Maria Frank-Kamenetsky; Svetlana Shulga-Morskaya; Abigail Liebow; Brian R Bettencourt; Jessica E Sutherland; Renta M Hutabarat; Valerie A Clausen; Verena Karsten; Jeffrey Cehelsky; Saraswathy V Nochur; Victor Kotelianski; Jay Horton; Timothy Mant; Joseph Chiesa; James Ritter; Malathy Munisamy; Akshay K Vaishnaw; Jared A Gollob; Amy Simon Journal: Lancet Date: 2013-10-03 Impact factor: 79.321
Authors: Abdullah K Altwairgi; Waleed A Alghareeb; Fouad H AlNajjar; Hussain Alhussain; Eyad Alsaeed; Ali Abdullah O Balbaid; Sadeq Aldanan; Yasser Orz; Abdullah A Alsharm Journal: Invest New Drugs Date: 2020-08-27 Impact factor: 3.850
Authors: Paul Garner; Sally Hopewell; Jackie Chandler; Harriet MacLehose; Holger J Schünemann; Elie A Akl; Joseph Beyene; Stephanie Chang; Rachel Churchill; Karin Dearness; Gordon Guyatt; Carol Lefebvre; Beth Liles; Rachel Marshall; Laura Martínez García; Chris Mavergames; Mona Nasser; Amir Qaseem; Margaret Sampson; Karla Soares-Weiser; Yemisi Takwoingi; Lehana Thabane; Marialena Trivella; Peter Tugwell; Emma Welsh; Ed C Wilson; Holger J Schünemann Journal: BMJ Date: 2016-07-20