Statins for the primary prevention of cardiovascular disease.
BACKGROUND
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.


OBJECTIVE
To assess the effects, both harms and benefits, of statins in people with no history of CVD.


METHODS
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.


METHODS
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.


METHODS
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.


RESULTS
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.


CONCLUSIONS
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK, WC1E 7HT.
Fiona
F
Taylor
Kirsten
K
Ward
Theresa Hm
TH
Moore
Margaret
M
Burke
George
G
Davey Smith
Juan-Pablo
JP
Casas
Shah
S
Ebrahim
D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D002423:Cause of Death; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011322:Primary Prevention; D016032:Randomized Controlled Trials as Topic
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Schweiz Med Wochenschr. 1993 Sep 18;123(37):1736-41
8211024
Clin Chim Acta. 2001 Oct;312(1-2):41-7
11580908
Lancet. 2003 Feb 1;361(9355):428; author reply 428
12573397
J Am Coll Cardiol. 1999 Apr;33(5):1294-304
10193730
Lancet. 2001 Mar 17;357(9259):881
11265973
JAMA. 2005 Nov 2;294(17):2203-9
16264162
BMJ. 1995 Apr 29;310(6987):1105-9
7742677
Circulation. 2009 Jan 27;119(3):382-9
19139385
Circulation. 2001 Nov 27;104(22):2746-53
11723030
Qual Health Care. 1998 Dec;7(4):232-9
10339027
N Engl J Med. 1990 Oct 4;323(14):946-55
2205799
Am J Cardiol. 1997 Mar 15;79(6):756-62
9070554
J Atheroscler Thromb. 1996;3(2):95-104
9226461
BMJ. 2004 Feb 14;328(7436):385-6
14962875
N Engl J Med. 2008 Nov 20;359(21):2280-2
18997195
Am J Cardiol. 1991 Nov 1;68(11):1127-31
1951069
Lancet. 2007 Dec 1;370(9602):1829-39
18061058
Am J Cardiol. 2000 Sep 1;86(5):514-8
11009268
J Cardiovasc Pharmacol Ther. 1997 Jan;2(1):7-16
10684437
Am J Cardiol. 1999 Nov 15;84(10):1192-7
10569329
N Engl J Med. 1995 Feb 23;332(8):488-93
7830729
Circulation. 1995 Oct 1;92(7):1758-64
7671358
Circulation. 2004 Nov 2;110(18):2809-16
15492322
Kidney Int. 1993 Nov;44(5):1124-9
8264145
Cardiovasc J S Afr. 2003 Jan-Feb;14(1):48
12728925
Nephrol Dial Transplant. 2000 May;15(5):684-8
10809811
Ann Surg. 1992 Oct;216(4):389-98; discussion 398-400
1417188
Psychosomatics. 2003 Sep-Oct;44(5):412-4
12954916
N Engl J Med. 2008 Nov 20;359(21):2195-207
18997196
Int J Epidemiol. 1997 Dec;26(6):1191-202
9447398
JAMA. 1992 Jan 1;267(1):70-6
1727199
Lancet. 2003 Mar 29;361(9363):1135; author reply 1136
12672345
Arch Intern Med. 2004 Jul 12;164(13):1427-36
15249352
BMJ. 1991 Aug 3;303(6797):276-82
1888927
BMJ. 2006 Jun 17;332(7555):1419
16737980
JAMA. 1999 Dec 22-29;282(24):2340-6
10612322
Health Technol Assess. 1999;3(19):i-iv, 1-91
10576067
Rev Med Liege. 2002 Dec;57(12):809-13
12632840
N Engl J Med. 1999 Jul 8;341(2):70-6
10395630
Circulation. 1994 Oct;90(4):1679-87
7734010
J Hypertens. 2001 Jun;19(6):1139-47
11403364
BMJ. 1997 Dec 13;315(7122):1577-82
9437275
Lancet. 1998 Jan 24;351(9098):233-41
9457092
Health Technol Assess. 2005 Oct;9(38):iii-iv, ix-x, 1-152
16181564
Circulation. 2001 Apr 3;103(13):1721-6
11282901
BMJ. 2003 Oct 4;327(7418):788
14525878
Circulation. 2003 Sep 23;108(12):1481-6
12952839
Circulation. 2006 Dec 19;114(25):2788-97
17159064
Am J Cardiol. 1998 Mar 1;81(5):582-7
9514454
Br J Clin Pharmacol. 2004 May;57(5):640-51
15089818
JAMA. 2003 Aug 20;290(7):921-8
12928469
Lancet. 2005 Oct 8;366(9493):1267-78
16214597
BMJ. 2009 Jun 30;338:b2376
19567909
Diabet Med. 2002 Mar;19(3):201-11
11918622
Am J Med. 1996 Dec;101(6):627-34
9003110
Int J Clin Pharmacol Ther. 2003 Dec;41(12):567-77
14692706
JAMA. 2006 Jan 4;295(1):74-80
16391219
Lancet. 2003 Jun 14;361(9374):2005-16
12814710
J Intern Med. 1998 May;243(5):373-80
9651560
Stroke. 2004 Dec;35(12):2807-12
15514192
Am J Med. 2004 Oct 15;117(8):596-606
15465509
Ann Intern Med. 1994 Apr 1;120(7):537-43
8093139
Am J Cardiol. 1997 Nov 15;80(10):1391-4
9388128
J Intern Med. 1996 Jul;240(1):13-22
8708586
Lancet. 2007 Dec 15;370(9604):2054-62
18063025
JAMA. 1992 Sep 16;268(11):1429-33
1512911
BMJ. 2003 Jun 28;326(7404):1423
12829554
Circulation. 2003 Feb 11;107(5):757-61
12578881
Am J Cardiol. 1996 Jan 1;77(1):83-5
8540464
Arch Intern Med. 2002 Jun 24;162(12):1395-400
12076239
J Am Coll Cardiol. 1995 Aug;26(2):351-7
7608434
Am J Med. 1991 Jul 31;91(1B):18S-24S
1867232
Am J Cardiol. 1993 Nov 1;72(14):1031-7
8213583
Health Aff (Millwood). 2007 Jan-Feb;26(1):13-24
17211010
Arch Intern Med. 2010 Jun 28;170(12):1024-31
20585067
J Atheroscler Thromb. 2002;9(2):99-108
12236319
Eur Heart J. 1997 Nov;18(11):1718-24
9402445
Br J Clin Pharmacol. 2001 Oct;52(4):439-46
11678788
J Am Coll Cardiol. 2002 Feb 20;39(4):610-6
11849859
Curr Control Trials Cardiovasc Med. 2002 May 20;3(1):8
12097148
Clin Ther. 2003 Apr;25(4):1107-22
12809960
Clin Ther. 2006 Jan;28(1):26-35
16490577
Horm Res. 2000;53(3):120-4
11044791
Lancet. 1996 Aug 10;348(9024):387-8
8709740
Am J Cardiol. 1990 Sep 18;66(8):44B-55B
2206036
Arch Intern Med. 1994 Mar 14;154(5):529-39
8122946
Clin Exp Pharmacol Physiol. 2001 May-Jun;28(5-6):409-18
11380515
Atherosclerosis. 1993 Feb;99(1):47-53
8461059
J Clin Epidemiol. 2007 Sep;60(9):869-73
17689802
Arch Intern Med. 1991 Jan;151(1):43-9
1985608
BMJ. 1996 Jul 13;313(7049):75-8
8688757
Lancet. 2002 Nov 23;360(9346):1623-30
12457784
Atheroscler Suppl. 2003 Dec;4(5):17-22
14980231
Lancet. 2003 Apr 5;361(9364):1149-58
12686036
Atherosclerosis. 2005 Feb;178(2):387-97
15694949
Lancet. 2002 Nov 2;360(9343):1347-60
12423980
Am J Epidemiol. 1997 Oct 1;146(7):558-64
9326433
Circulation. 1998 Apr 21;97(15):1440-5
9576423
JAMA. 2002 Dec 18;288(23):2998-3007
12479764
Clin Cardiol. 1991 Feb;14(2):146-51
1904333
J Hum Hypertens. 2001 Aug;15 Suppl 1:S11-2
11685901
N Engl J Med. 2001 Jun 28;344(26):1959-65
11430324
Heart. 2003 Mar;89(3):327-8
12591845
J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):385-9
12235304
Health Technol Assess. 2007 Apr;11(14):1-160, iii-iv
17408535
Stroke. 1997 May;28(5):946-50
9158630
BMJ. 1994 Nov 12;309(6964):1286-91
7718048
Lancet. 2002 Nov 23;360(9346):1618-9
12457780
Kidney Int Suppl. 1999 Jul;71:S113-6
10412752
Am J Cardiol. 1997 Jun 1;79(11):1475-81
9185636
Lancet. 2007 Jan 20;369(9557):168-9
17240267
Control Clin Trials. 2002 Dec;23(6):757-73
12505250
Int J Clin Pharmacol Ther. 1995 Jun;33(6):345-50
7582386
J Intern Med. 1998 Nov;244(5):371-8
9845852
Circ J. 2004 Sep;68(9):860-7
15329509
Diabetes Obes Metab. 2000 Dec;2(6):355-62
11225965
Arch Intern Med. 2006 Nov 27;166(21):2307-13
17130382
N Engl J Med. 1995 Nov 16;333(20):1301-7
7566020
Lancet. 1996 Nov 16;348(9038):1339-42
8918276
Am J Med. 2000 May;108(7):538-46
10806282
Am J Transplant. 2004 Jun;4(6):988-95
15147434
Lancet. 2004 Aug 21-27;364(9435):685-96
15325833
J Am Coll Cardiol. 2008 Nov 25;52(22):1769-81
19022156
Am J Epidemiol. 1999 Mar 1;149(5):429-41
10067902
J Am Geriatr Soc. 1997 Jan;45(1):8-14
8994481
BMJ. 2000 Oct 21;321(7267):983-6
11039962
BMJ. 2001 Jan 6;322(7277):11-5
11141142
Am J Cardiol. 1994 Oct 1;74(7):667-73
7942524
Hypertension. 1996 Oct;28(4):647-51
8843892
J Clin Epidemiol. 1992 Aug;45(8):849-60
1624967
Atherosclerosis. 2002 Jul;163(1):157-64
12048134
JAMA. 1998 May 27;279(20):1615-22
9613910
Circulation. 1994 Jun;89(6):2519-24
8205659
Tidsskr Nor Laegeforen. 2004 Jan 22;124(2):165-6
14743227
Diabetes Care. 2006 Jul;29(7):1478-85
16801565
Atherosclerosis. 2000 Aug;151(2):575-83
10924737
Lancet. 2010 Nov 13;376(9753):1670-81
21067804