Lancet 2005 366: 1267-1134 doi:10.1016/S0140-6736(08)60104-X Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from.

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Lancet : doi: /S (08)60104-X Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins

Events (%) Cause of death TreatmentControl Rate Ratio (CI) Vascular causes CHD1548 (3·4)1960 (4·4) Stroke265 (0·6)291 (0·6) Other vascular289 (0·6)302 (0·7) Any non-CHD vascular554 (1·2)593 (1·3) Any vascular 2102 (4·7)2553 (5·7) Non-vascular causes Cancer1094 (2·4)1069 (2·4) Trauma 51 (0·1)57 (0·1) Other/unknown487 (1·1)550 (1·2) Any non-vascular1730 (3·8)1801 (4·0) ANY DEATH3832 (8·5)4354 (9·7) 0·5 1·01·5 Respiratory 98 (0·2)125 (0·3) 0·81 (0·76 – 0·85) 0·91 (0·74 – 1·11) 0·95 (0·78 – 1·16) 0·93 (0·83 – 1·03) 0·83 (0·79 – 0·87) 1·01 (0·91 – 1·12) 0·89 (0·59 – 1·34) 0·82 (0·62 – 1·08) 0·87 (0·73 – 1·03) 0·95 (0·90 – 1·01) 0·88 (0·84 – 0·91) RR (95% CI) RR (99% CI) Effects on CAUSE-SPECIFIC MORTALITY per mmol/L LDL cholesterol reduction

Relation between the proportional reduction in MAJOR VASCULAR EVENTS and mean absolute LDL reduction in 14 statin trials

Endpoint Events (%) TreatmentControl Rate Ratio (CI) Non-fatal MI2001 (4·4)2769 (6·2) 0·74 (0·70 – 0·79) CHD death1548 (3·4)1960 (4·4) 0·81 (0·75 – 0·87) Any major coronary event3337 (7·4)4420 (9·8)0·77 (0·74 – 0·80) CABG713 (3·3)1006 (4·7) 0·75 (0·69 – 0·82) PTCA510 (2·4)658 (3·1) 0·79 (0·69 – 0·90) Unspecified1397 (3·1)1770 (3·9) 0·76 (0·69 – 0·84) Any coronary revascularisation2620 (5·8)3434 (7·6)0·76 (0·73 – 0·80) Haemorrhagic stroke105 (0·2)99 (0·2) 1·05 (0·78 – 1·41) Presumed ischaemic stroke1235 (2·8)1518 (3·4) 0·81 (0·74 – 0·89) Any stroke1340 (3·0)1617 (3·7)0·83 (0·78 – 0·88) Any major vascular event6354 (14·1)7994 (17·8)0·79 (0·77 – 0·81) 0·51·01·5 RR (95% CI) RR (99% CI) Effects on MAJOR VASCULAR EVENTS per mmol/L LDL cholesterol reduction

Groups Events (%) Treatment Control 0·51·01·5 Rate Ratio (CI) Prior disease Post MI Other CHD None Age (years) 65 >65 Gender Male Female Treated hypertension Yes No History of diabetes Yes No Diastolic blood pressure (mm Hg) 90 >90 Prior disease 3051 (21·2)3860 (26·9) 1257 (19·3)1581 (24·2) None2046 (8·5)2553 (10·6) ≤ 3454 (12·5)4448 (16·2) 2900 (16·6)3546 (20·3) Male5097 (14·9)6504 (19·0) Female1257 (11·7)1490 (13·8) Yes3925 (15·8)4783 (19·2) 2429 (12·0)3211 (15·9) 1465 (15·6)1782 (19·2) No4889 (13·7)6212 (17·4) (14·9)6493 (18·6) 1154 (11·4)1496 (14·8) ≤ 0·79 (0·75 – 0·83) 0·80 (0·73 – 0·87) 0·78 (0·72 – 0·84) 0·78 (0·74 – 0·82) 0·81 (0·77 – 0·86) 0·78 (0·75 – 0·81) 0·83 (0·76 – 0·91) 0·81 (0·77 – 0·85) 0·77 (0·73 – 0·82) 0·79 (0·72 – 0·86) 0·79 (0·76 – 0·82) 0·79 (0·76 – 0·83) 0·77 (0·80 – 0·84) p< Overall 6354 (14·1) 7994 (17·8)0·79 (0·77 – 0·81) RR (95% CI) RR (99% CI) Effects on MAJOR VASCULAR EVENTS per mmol/L LDL cholesterol reduction, subdivided by baseline prognostic factors (1)

Groups Events (%) TreatmentControl Rate Ratio (CI) Total cholesterol (mmol/L) (13·5)1808 (16·6) 0·76 (0·69 – 0·85) (13·9)4159 (17·4) 0·79 (0·75 – 0·83) > (15·2)1992 (19·7)0·80 (0·76 – 0·86) LDL cholesterol (mmol/L) (13·4)2776 (16·7)0·76 (0·71 – 0·82) (14·2)3344 (17·6) 0·79 (0·75 – 0·84) > (15·8)1773 (20·4) 0·81 (0·76 – 0·87) HDL cholesterol (mmol/L) (18·2)2876 (22·7) 0·78 (0·73 – 0·83) (14·3)2278 (18·2) 0·79 (0·74 – 0·84) > (11·4)2789 (14·2) 0·79 (0·75 – 0·85) Triglycerides (mmol/L) (13·4)2665 (16·8) 0·79 (0·74 – 0·85) (13·8)2389 (18·0) 0·78 (0·73 – 0·83) > (15·3)2868 (18·8) 0·80 (0·74 – 0·85) 6354 (14·1)7994 (17·8)0·79 (0·77 – 0·81) 0·51·01·5 Effects on MAJOR VASCULAR EVENTS per mmol/L LDL cholesterol reduction, subdivided by baseline prognostic factors (2) Overall p< RR (95% CI) RR (99% CI) ≤ ≤ ≤ ≤

0·72 (0·67 – 0·78) 0·78 (0·73 – 0·83) 0·90 (0.85 – 0·96) Endpoint Events (%) TreatmentControl Rate Ratio (CI) YEAR (3·9)1951 (4·3) YEAR (2·9)1603 (3·8) YEAR (2·8) 1543 (3·9)0·74 (0·69 – 0·79) YEAR (2·6)1306 (3·8) YEAR (2·9)993 (3·7)0·79 (0·74 – 0·86) YEAR (2·8) 598 (3·8) 0·74 (0·67 – 0·82) 0·5 1·01·5 p< RR (95% CI) Effects on MAJOR VASCULAR EVENTS per mmol/L LDL cholesterol reduction, by year

Site of first cancer Events (%) TreatmentControl Rate Ratio (CI) Gastrointestinal543 (1·4)512 (1·3) 1·03 (0·90 - 1·17) Genitourinary760 (1·9)775 (1·9) 0·97 (0·87 - 1·09) Respiratory372 (0·9)390 (1·0) 0·97 (0·83 - 1·14) Breast (women)105 (1·1)92 (0·9) 1·09 (0·79 - 1·49) Haematological97 (0·3)106 (0·4) 0·94 (0·67 - 1·32) Melanoma77 (0·2)80 (0·2) 1·03 (0·71 - 1·50) Other/unknown613 (1·5)581 (1·5) 1·08 (0·90 - 1·29) Any site2567 (6·4)2536 (6·4) 1·00 (0·95 - 1·06) 0·51·01·5 p = 0.9 RR (95% CI) RR (99% CI) Effects on CANCER incidence per mmol/L LDL cholesterol by site

Events (%) TreatmentControl Rate Ratio (CI) 0-1 year412 (1·0)441 (1·1) 0·95 (0·81 – 1·12) 1-2 years532 (1·4)513 (1·3) 1·03 (0·89 – 1·20) 2-3 years512 (1·4)514 (1·4) 0·99 (0·85 – 1·15) 3-4 years494 (1·4)476 (1·4) 1·00 (0·86 – 1·16) 4-5 years384 (1·3)374 (1·3) 1·02 (0·86 – 1·21) 5+ years233 (1·3)218 (1·2) 1·05 (0·84 – 1·32) All times2567 (6·4)2536 (6·4) 1·00 (0·95 –1·06) 0·51·01·5 p = 0.9 RR (95% CI) RR (99% CI) Effects on CANCER incidence per mmol/L LDL cholesterol by year

Additional Slides

Outcomes avoided per 1000 (95% CI) 27 (20-34) 8 (4-12) 48 (39-57) revascularisation Stroke Major coronary events Coronary Major vascular events 30 (24-37) 5 year absolute benefits on particular vascular outcomes per mmol/l LDL cholesterol reduction in participants WITH previous MI or CHD Event Rate (%)

Outcomes avoided per 1000 (95% CI) 12 (9-16) 5 (1-8) 25 (19-31) Coronary revascularisation StrokeMajor vascular events Major coronary events 18 (14-23) 5 year absolute benefits on particular vascular outcomes per mmol/l LDL cholesterol reduction in participants WITHOUT previous MI or CHD Event Rate (%)

Groups Treatment Control Rate Ratio (CI) Prior disease Post-MI 1681 (11·7)2207 (15·4) 0·78 (0·74 – 0·84) Other CHD 568 (8·7) 744 (11·4)0·77 (0·68 – 0·87) None 1088 (4·5) 1469 (6·1) 0·72 (0·66 – 0·80) Age (years) (6·1)2344 (8·5)0·74 (0·69 – 0·79) > (9·5)2076 (11·9) 0·81 (0·76 – 0·88) Gender Male2686 (7·8)3630 (10·6) 0·76 (0·72 – 0·80) Female 651 (6·1)790 (7·3) Treated hypertension Yes 2038 (8·2)2596 (10·4) 0·79 (0·74 – 0·84) No 1299 (6·4)1824 (9·1) 0·75 (0·70 – 0·81) History of diabetes Yes 776 (8·3)979 (10·5) 0·78 (0·69 – 0·87) No 2561 (7·2)3441 (9·6)0·77 (0·73 – 0·81) Diastolic blood pressure (mmHg) (7·8)3590 (10·3) 0·77 (0·73 – 0·81) > (6·1)827 (8·2) 0·76 (0·68 – 0·85) 0·5 1·01·5 0·82 (0·73 – 0·93) Effects on MAJOR CORONARY EVENTS per mmol/L LDL cholesterol reduction, subdivided by baseline prognostic factors (1) Overall 3337 (7·4) 4420 (7·4) 0·77 (0·74 – 0·80) p< RR (95% CI) RR (99% CI) ≤ ≤

Groups Treatment Control Rate Ratio (CI) Total cholesterol (mmol/L) (6·9)940 (8·6) 0·76 (0·66 – 0·88) (7·0)2246 (9·4) 0·76 (0·71 – 0·82) > (8·8)1220 (12·1) 0·78 (0·72 – 0·84) LDL cholesterol (mmol/L) (6·8)1443 (8·7) 0·76 (0·68 – 0·84) (7·3)1814 (9·6)0·77 (0·71 – 0·83) > (9·3)1120 (12·9) 0·78 (0·72 – 0·85) HDL cholesterol (mmol/L) (9·3)1538 (12·1)0·76 (0·70 – 0·84) (7·4)1270 (10·2) 0·76 (0·70 – 0·83) > (6·2)1595 (8·1) 0·77 (0·71 – 0·84) Triglycerides (mmol/L) (7·3)1521 (9·6) 0·78 (0·71 – 0·85) (7·1) 1304 (9·8)0·77 (0·71 – 0·84) > (7·9) 1564 (10·2)0·76 (0·69 – 0·83) Overall 3337 (7·4)4420 (9·8) 0·77 (0·74 – 0·80) 0·5 1·01·5 p< Effects on MAJOR CORONARY EVENTS per mmol/L LDL cholesterol reduction, subdivided by baseline prognostic factors (2) RR (95% CI) RR (99% CI) ≤ ≤ ≤ ≤