schliessen

Filtern

 

Bibliotheken

Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

Summary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandi... Full description

Journal Title: Lancet 2017, Vol.389 (10088), p.2473-2481
Main Author: Gupta, Ajay, MRCP
Other Authors: Thompson, David, MRCPI , Whitehouse, Andrew, MBBS , Collier, Tim, MSc , Dahlof, Bjorn, MD , Poulter, Neil, Prof , Collins, Rory, Prof , Sever, Peter, Prof
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 0140-6736
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_swepub_primary_oai_gup_ub_gu_se_255427
title: Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
format: Article
creator:
  • Gupta, Ajay, MRCP
  • Thompson, David, MRCPI
  • Whitehouse, Andrew, MBBS
  • Collier, Tim, MSc
  • Dahlof, Bjorn, MD
  • Poulter, Neil, Prof
  • Collins, Rory, Prof
  • Sever, Peter, Prof
subjects:
  • 11 Medical And Health Sciences
  • Abridged Index Medicus
  • Adult
  • Aged
  • Analysis
  • Angina
  • ASCOT Investigators
  • Atorvastatin
  • Atorvastatin - administration & dosage
  • Atorvastatin - adverse effects
  • Cardiac patients
  • Cardiovascular disease
  • Cardiovascular diseases
  • Cholesterol
  • Clinical Medicine
  • Clinical trials
  • Cognitive ability
  • Complications and side effects
  • Connective tissues
  • Disorders
  • Disturbance
  • Doctors
  • Double-Blind Method
  • Early Termination of Clinical Trials
  • Effectiveness
  • Epidemiology
  • Erectile dysfunction
  • Evidence-based medicine
  • Fasting
  • Female
  • Funding
  • General & Internal
  • General & Internal Medicine
  • Health risk assessment
  • Health risks
  • Heart
  • Heart diseases
  • Hematologic Diseases - chemically induced
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
  • Hypercholesterolemia - prevention & control
  • Hypertension
  • Hypertension - complications
  • Hypolipidemic Agents - administration & dosage
  • Hypolipidemic Agents - adverse effects
  • Impairment
  • Internal Medicine
  • intolerance
  • Kidney transplantation
  • Kidneys
  • Klinisk medicin
  • Laboratories
  • Life Sciences & Biomedicine
  • Lipids
  • Low density lipoprotein
  • Lymphatic Diseases - chemically induced
  • Lymphatic system
  • Male
  • management
  • Matching
  • Medical personnel
  • Medical research
  • Medicine
  • Medicine, Experimental
  • Middle Aged
  • Muscular Diseases - chemically induced
  • Myocardial infarction
  • Nocebo Effect
  • Nocebos
  • participants
  • Patients
  • Physicians
  • prevention
  • Public health
  • risk
  • Risk analysis
  • Risk Factors
  • Science & Technology
  • Sexual disorders
  • Side effects
  • Sleep
  • Sleep Wake Disorders
  • Statins
  • Therapy
  • Treatment Outcome
ispartof: Lancet, 2017, Vol.389 (10088), p.2473-2481
description: Summary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88–1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75–1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56–0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57–1·54]; p=0·8
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.8244324
LOCALfalse
PrimoNMBib
record
control
sourceidgale_swepu
recordidTN_cdi_swepub_primary_oai_gup_ub_gu_se_255427
sourceformatXML
sourcesystemPC
galeidA498031714
sourcerecordidA498031714
originalsourceidFETCH-LOGICAL-1859t-79817b375e52258817db63aa461955eab0087285dc306d7d983e7c68ecaef9633
addsrcrecordideNqNk19P1TAYxqeRKKIfQdPEG0gYttu6bppoToj_khO5ABPvmq59dyjutLPtDnLnh_AT-knsmMKBECFLtvXd8_zate-TJM8I3iOYlC8PMSlwWrK83CZsJyeY0bS-n2ySghUpLdjXB8nmheRR8tj7E4xxUWL6MHmUVQUrs6ravLcxUytwHhCswASPhPdWahFAoVMdjtFgmk4bBWoXNUNAxoapflH1QQRtUDgGJ_ozNL2imVl0Nj2UwihtxEoLg_aFU1pIdDAEaZfg0ZHTovv989dc91qlc3sKTpsFmrkl2p4d7h8cpfP5bOcVEshFjF1qHxel7NB0kJ5Pj_pOSGhsKq0JznZd_B5GKIp6pOPfGGvSNfM4nJzwI4Dx2hrUHwsPT5KNVnQenv59biVf3r872v-Yzg8-fNqfzVNS0TqkrK4Ia3JGgWYZreJANWUuRFGSmlIQDcYVyyqqZI5LxVRd5cBkWYEU0NZlnm8l6cT1p9APDe-dXgp3xq3QfDH0PJYWA_fAM0qLjEX950lvezBCO7jiUAYCj4cQjactx5hwioVqFRaCUtE0dU2qluR1WbUgZBv7IAK3J2Dv7PcBfOBxZyR0nTBgB89JVZc4r_Isi9IX16QndnAmbg8nNcnKMgqLS9VCdMC1aW1wQo5QPqMZYbhg2f9VRV3hnDAyqvZuUMVLwVLHM4ZWx_oV7J0M6zM8v8HA14k3CtYJu2uCZvDagI83rxfHwS_E4P3VFd5Bvk6nk1w6672D9uK8CeZj7Pl57PmYaU4YP489ry-XHZtqCerC9S_nUfD6GljqMbhjcITubsW_ndwQs7HS4LiXGowEFVtSxh60-lbCm2sEGXOopei-wRn4y87iPuN4gowMws4Jdf4HNU2LnA
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid1912666034
display
typearticle
titleAdverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
sourceAlma/SFX Local Collection
creatorGupta, Ajay, MRCP ; Thompson, David, MRCPI ; Whitehouse, Andrew, MBBS ; Collier, Tim, MSc ; Dahlof, Bjorn, MD ; Poulter, Neil, Prof ; Collins, Rory, Prof ; Sever, Peter, Prof
creatorcontribGupta, Ajay, MRCP ; Thompson, David, MRCPI ; Whitehouse, Andrew, MBBS ; Collier, Tim, MSc ; Dahlof, Bjorn, MD ; Poulter, Neil, Prof ; Collins, Rory, Prof ; Sever, Peter, Prof ; ASCOT Investigators ; Sahlgrenska akademin ; Institute of Medicine, Department of Molecular and Clinical Medicine ; Institutionen för medicin, avdelningen för molekylär och klinisk medicin ; Göteborgs universitet ; Gothenburg University ; Sahlgrenska Academy
descriptionSummary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88–1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75–1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56–0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57–1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08–1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10–1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06–1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04–1·88]; p=0·03), which were reported more commonly by statin users than by non-users. Interpretation These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. these results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Funding Pfizer, Servier Research Group, and Leo Laboratories.
identifier
0ISSN: 0140-6736
1EISSN: 1474-547X
2DOI: 10.1016/S0140-6736(17)31075-9
3PMID: 28476288
languageeng
publisherEngland: Elsevier Ltd
subject
ispartofLancet, 2017, Vol.389 (10088), p.2473-2481
rights
0Elsevier Ltd
12017 Elsevier Ltd
2Copyright © 2017 Elsevier Ltd. All rights reserved.
3COPYRIGHT 2017 Elsevier B.V.
4Copyright Elsevier Limited Jun 24, 2017
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1859t-79817b375e52258817db63aa461955eab0087285dc306d7d983e7c68ecaef9633
citesFETCH-LOGICAL-1859t-79817b375e52258817db63aa461955eab0087285dc306d7d983e7c68ecaef9633
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28476288$$D View this record in MEDLINE/PubMed
1$$Uhttps://gup.ub.gu.se/publication/255427$$DView record from Swedish Publication Index
search
creatorcontrib
0Gupta, Ajay, MRCP
1Thompson, David, MRCPI
2Whitehouse, Andrew, MBBS
3Collier, Tim, MSc
4Dahlof, Bjorn, MD
5Poulter, Neil, Prof
6Collins, Rory, Prof
7Sever, Peter, Prof
8ASCOT Investigators
9Sahlgrenska akademin
10Institute of Medicine, Department of Molecular and Clinical Medicine
11Institutionen för medicin, avdelningen för molekylär och klinisk medicin
12Göteborgs universitet
13Gothenburg University
14Sahlgrenska Academy
title
0Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
1Lancet
addtitleLancet
descriptionSummary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88–1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75–1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56–0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57–1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08–1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10–1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06–1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04–1·88]; p=0·03), which were reported more commonly by statin users than by non-users. Interpretation These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. these results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Funding Pfizer, Servier Research Group, and Leo Laboratories.
subject
011 Medical And Health Sciences
1Abridged Index Medicus
2Adult
3Aged
4Analysis
5Angina
6ASCOT Investigators
7Atorvastatin
8Atorvastatin - administration & dosage
9Atorvastatin - adverse effects
10Cardiac patients
11Cardiovascular disease
12Cardiovascular diseases
13Cholesterol
14Clinical Medicine
15Clinical trials
16Cognitive ability
17Complications and side effects
18Connective tissues
19Disorders
20Disturbance
21Doctors
22Double-Blind Method
23Early Termination of Clinical Trials
24Effectiveness
25Epidemiology
26Erectile dysfunction
27Evidence-based medicine
28Fasting
29Female
30Funding
31General & Internal
32General & Internal Medicine
33Health risk assessment
34Health risks
35Heart
36Heart diseases
37Hematologic Diseases - chemically induced
38Humans
39Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
40Hypercholesterolemia - prevention & control
41Hypertension
42Hypertension - complications
43Hypolipidemic Agents - administration & dosage
44Hypolipidemic Agents - adverse effects
45Impairment
46Internal Medicine
47intolerance
48Kidney transplantation
49Kidneys
50Klinisk medicin
51Laboratories
52Life Sciences & Biomedicine
53Lipids
54Low density lipoprotein
55Lymphatic Diseases - chemically induced
56Lymphatic system
57Male
58management
59Matching
60Medical personnel
61Medical research
62Medicine
63Medicine, Experimental
64Middle Aged
65Muscular Diseases - chemically induced
66Myocardial infarction
67Nocebo Effect
68Nocebos
69participants
70Patients
71Physicians
72prevention
73Public health
74risk
75Risk analysis
76Risk Factors
77Science & Technology
78Sexual disorders
79Side effects
80Sleep
81Sleep Wake Disorders
82Statins
83Therapy
84Treatment Outcome
issn
00140-6736
11474-547X
fulltexttrue
rsrctypearticle
creationdate2017
recordtypearticle
recordideNqNk19P1TAYxqeRKKIfQdPEG0gYttu6bppoToj_khO5ABPvmq59dyjutLPtDnLnh_AT-knsmMKBECFLtvXd8_zate-TJM8I3iOYlC8PMSlwWrK83CZsJyeY0bS-n2ySghUpLdjXB8nmheRR8tj7E4xxUWL6MHmUVQUrs6ravLcxUytwHhCswASPhPdWahFAoVMdjtFgmk4bBWoXNUNAxoapflH1QQRtUDgGJ_ozNL2imVl0Nj2UwihtxEoLg_aFU1pIdDAEaZfg0ZHTovv989dc91qlc3sKTpsFmrkl2p4d7h8cpfP5bOcVEshFjF1qHxel7NB0kJ5Pj_pOSGhsKq0JznZd_B5GKIp6pOPfGGvSNfM4nJzwI4Dx2hrUHwsPT5KNVnQenv59biVf3r872v-Yzg8-fNqfzVNS0TqkrK4Ia3JGgWYZreJANWUuRFGSmlIQDcYVyyqqZI5LxVRd5cBkWYEU0NZlnm8l6cT1p9APDe-dXgp3xq3QfDH0PJYWA_fAM0qLjEX950lvezBCO7jiUAYCj4cQjactx5hwioVqFRaCUtE0dU2qluR1WbUgZBv7IAK3J2Dv7PcBfOBxZyR0nTBgB89JVZc4r_Isi9IX16QndnAmbg8nNcnKMgqLS9VCdMC1aW1wQo5QPqMZYbhg2f9VRV3hnDAyqvZuUMVLwVLHM4ZWx_oV7J0M6zM8v8HA14k3CtYJu2uCZvDagI83rxfHwS_E4P3VFd5Bvk6nk1w6672D9uK8CeZj7Pl57PmYaU4YP489ry-XHZtqCerC9S_nUfD6GljqMbhjcITubsW_ndwQs7HS4LiXGowEFVtSxh60-lbCm2sEGXOopei-wRn4y87iPuN4gowMws4Jdf4HNU2LnA
startdate2017
enddate2017
creator
0Gupta, Ajay, MRCP
1Thompson, David, MRCPI
2Whitehouse, Andrew, MBBS
3Collier, Tim, MSc
4Dahlof, Bjorn, MD
5Poulter, Neil, Prof
6Collins, Rory, Prof
7Sever, Peter, Prof
general
0Elsevier Ltd
1Elsevier B.V
2Elsevier Limited
3Elsevier
scope
0CGR
1CUY
2CVF
3ECM
4EIF
5NPM
6AAYXX
7CITATION
8BKMMT
9BSHEE
100TT
110TZ
120U~
133V.
147QL
157QP
167RV
177TK
187U7
197U9
207X7
217XB
2288A
2388C
2488E
2588G
2688I
278AF
288AO
298C1
308C2
318FE
328FH
338FI
348FJ
358FK
368G5
37ABUWG
38AN0
39ASE
40AZQEC
41BBNVY
42BEC
43BENPR
44BHPHI
45C1K
46DWQXO
47FPQ
48FYUFA
49GHDGH
50GNUQQ
51GUQSH
52H94
53HCIFZ
54K6X
55K9-
56K9.
57KB0
58KB~
59LK8
60M0R
61M0S
62M0T
63M1P
64M2M
65M2O
66M2P
67M7N
68M7P
69MBDVC
70NAPCQ
71PQEST
72PQQKQ
73PQUKI
74Q9U
75S0X
767X8
77BOBZL
78CLFQK
79ADTPV
80AOWAS
sort
creationdate2017
titleAdverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
authorGupta, Ajay, MRCP ; Thompson, David, MRCPI ; Whitehouse, Andrew, MBBS ; Collier, Tim, MSc ; Dahlof, Bjorn, MD ; Poulter, Neil, Prof ; Collins, Rory, Prof ; Sever, Peter, Prof
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1859t-79817b375e52258817db63aa461955eab0087285dc306d7d983e7c68ecaef9633
rsrctypearticles
prefilterarticles
languageeng
creationdate2017
topic
011 Medical And Health Sciences
1Abridged Index Medicus
2Adult
3Aged
4Analysis
5Angina
6ASCOT Investigators
7Atorvastatin
8Atorvastatin - administration & dosage
9Atorvastatin - adverse effects
10Cardiac patients
11Cardiovascular disease
12Cardiovascular diseases
13Cholesterol
14Clinical Medicine
15Clinical trials
16Cognitive ability
17Complications and side effects
18Connective tissues
19Disorders
20Disturbance
21Doctors
22Double-Blind Method
23Early Termination of Clinical Trials
24Effectiveness
25Epidemiology
26Erectile dysfunction
27Evidence-based medicine
28Fasting
29Female
30Funding
31General & Internal
32General & Internal Medicine
33Health risk assessment
34Health risks
35Heart
36Heart diseases
37Hematologic Diseases - chemically induced
38Humans
39Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
40Hypercholesterolemia - prevention & control
41Hypertension
42Hypertension - complications
43Hypolipidemic Agents - administration & dosage
44Hypolipidemic Agents - adverse effects
45Impairment
46Internal Medicine
47intolerance
48Kidney transplantation
49Kidneys
50Klinisk medicin
51Laboratories
52Life Sciences & Biomedicine
53Lipids
54Low density lipoprotein
55Lymphatic Diseases - chemically induced
56Lymphatic system
57Male
58management
59Matching
60Medical personnel
61Medical research
62Medicine
63Medicine, Experimental
64Middle Aged
65Muscular Diseases - chemically induced
66Myocardial infarction
67Nocebo Effect
68Nocebos
69participants
70Patients
71Physicians
72prevention
73Public health
74risk
75Risk analysis
76Risk Factors
77Science & Technology
78Sexual disorders
79Side effects
80Sleep
81Sleep Wake Disorders
82Statins
83Therapy
84Treatment Outcome
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Gupta, Ajay, MRCP
1Thompson, David, MRCPI
2Whitehouse, Andrew, MBBS
3Collier, Tim, MSc
4Dahlof, Bjorn, MD
5Poulter, Neil, Prof
6Collins, Rory, Prof
7Sever, Peter, Prof
8ASCOT Investigators
9Sahlgrenska akademin
10Institute of Medicine, Department of Molecular and Clinical Medicine
11Institutionen för medicin, avdelningen för molekylär och klinisk medicin
12Göteborgs universitet
13Gothenburg University
14Sahlgrenska Academy
collection
0Medline
1MEDLINE
2MEDLINE (Ovid)
3MEDLINE
4MEDLINE
5PubMed
6CrossRef
7Gale General OneFile (A&I only)
8Academic OneFile (A&I only)
9News PRO
10Pharma and Biotech Premium PRO
11Global News & ABI/Inform Professional
12ProQuest Central (Corporate)
13Bacteriology Abstracts (Microbiology B)
14Calcium & Calcified Tissue Abstracts
15Nursing & Allied Health Database
16Neurosciences Abstracts
17Toxicology Abstracts
18Virology and AIDS Abstracts
19Health & Medical Collection
20ProQuest Central (purchase pre-March 2016)
21Biology Database (Alumni Edition)
22Healthcare Administration Database (Alumni)
23Medical Database (Alumni Edition)
24Psychology Database (Alumni)
25Science Database (Alumni Edition)
26STEM Database
27ProQuest Pharma Collection
28Public Health Database
29Lancet Titles
30ProQuest SciTech Collection
31ProQuest Natural Science Collection
32Hospital Premium Collection
33Hospital Premium Collection (Alumni Edition)
34ProQuest Central (Alumni) (purchase pre-March 2016)
35Research Library (Alumni Edition)
36ProQuest Central (Alumni Edition)
37British Nursing Database
38British Nursing Index
39ProQuest Central Essentials
40Biological Science Collection
41eLibrary
42ProQuest Central
43Natural Science Collection
44Environmental Sciences and Pollution Management
45ProQuest Central Korea
46British Nursing Index (BNI) (1985 to Present)
47Health Research Premium Collection
48Health Research Premium Collection (Alumni)
49ProQuest Central Student
50Research Library Prep
51AIDS and Cancer Research Abstracts
52SciTech Premium Collection
53British Nursing Index
54Consumer Health Database (Alumni Edition)
55ProQuest Health & Medical Complete (Alumni)
56Nursing & Allied Health Database (Alumni Edition)
57ProQuest Newsstand Professional
58ProQuest Biological Science Collection
59Consumer Health Database
60Health & Medical Collection (Alumni Edition)
61Healthcare Administration Database
62Medical Database
63Psychology Database
64Research Library
65Science Database
66Algology Mycology and Protozoology Abstracts (Microbiology C)
67Biological Science Database
68Research Library (Corporate)
69Nursing & Allied Health Premium
70ProQuest One Academic Eastern Edition
71ProQuest One Academic
72ProQuest One Academic UKI Edition
73ProQuest Central Basic
74SIRS Editorial
75MEDLINE - Academic
76OpenAIRE (Open Access)
77OpenAIRE
78SwePub
79SwePub Articles
jtitleLancet
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Gupta, Ajay, MRCP
1Thompson, David, MRCPI
2Whitehouse, Andrew, MBBS
3Collier, Tim, MSc
4Dahlof, Bjorn, MD
5Poulter, Neil, Prof
6Collins, Rory, Prof
7Sever, Peter, Prof
aucorp
0ASCOT Investigators
1Sahlgrenska akademin
2Institute of Medicine, Department of Molecular and Clinical Medicine
3Institutionen för medicin, avdelningen för molekylär och klinisk medicin
4Göteborgs universitet
5Gothenburg University
6Sahlgrenska Academy
formatjournal
genrearticle
ristypeJOUR
atitleAdverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase
jtitleLancet
addtitleLancet
date2017
risdate2017
volume389
issue10088
spage2473
epage2481
pages2473-2481
issn0140-6736
eissn1474-547X
abstractSummary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88–1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75–1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56–0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57–1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08–1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10–1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06–1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04–1·88]; p=0·03), which were reported more commonly by statin users than by non-users. Interpretation These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. these results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Funding Pfizer, Servier Research Group, and Leo Laboratories.
copEngland
pubElsevier Ltd
pmid28476288
doi10.1016/S0140-6736(17)31075-9
oafree_for_read