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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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Presentation on theme: "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."— Presentation transcript:

1 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 90,056 participants in 14 randomised trials of statins

2 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

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

4 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

5 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) 90 5191 (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<0.00001 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)

6 Groups Events (%) TreatmentControl Rate Ratio (CI) Total cholesterol (mmol/L) 5.21465 (13·5)1808 (16·6) 0·76 (0·69 – 0·85) 5.2-6.53312 (13·9)4159 (17·4) 0·79 (0·75 – 0·83) >6.51547 (15·2)1992 (19·7)0·80 (0·76 – 0·86) LDL cholesterol (mmol/L) 3.52237 (13·4)2776 (16·7)0·76 (0·71 – 0·82) 3.5-4.52680 (14·2)3344 (17·6) 0·79 (0·75 – 0·84) >4.51364 (15·8)1773 (20·4) 0·81 (0·76 – 0·87) HDL cholesterol (mmol/L) 0.92277 (18·2)2876 (22·7) 0·78 (0·73 – 0·83) 0.9-1.11813 (14·3)2278 (18·2) 0·79 (0·74 – 0·84) >1.1 2223 (11·4)2789 (14·2) 0·79 (0·75 – 0·85) Triglycerides (mmol/L) 1.42125 (13·4)2665 (16·8) 0·79 (0·74 – 0·85) 1.4-2.01821 (13·8)2389 (18·0) 0·78 (0·73 – 0·83) >2.02357 (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<0.00001 RR (95% CI) RR (99% CI) ≤ ≤ ≤ ≤

7 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 0-1 1747 (3·9)1951 (4·3) YEAR 1-2 1231 (2·9)1603 (3·8) YEAR 2-3 1151 (2·8) 1543 (3·9)0·74 (0·69 – 0·79) YEAR 3-4 946 (2·6)1306 (3·8) YEAR 4-5 811 (2·9)993 (3·7)0·79 (0·74 – 0·86) YEAR 5+ 468 (2·8) 598 (3·8) 0·74 (0·67 – 0·82) 0·5 1·01·5 p<0.00001 RR (95% CI) Effects on MAJOR VASCULAR EVENTS per mmol/L LDL cholesterol reduction, by year

8 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

9 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

10 Additional Slides

11 Outcomes avoided per 1000 (95% CI) 27 (20-34) 8 (4-12) 48 (39-57) 0 5 10 15 20 25 30 revascularisation Stroke 0 5 10 15 25 30 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 (%)

12 Outcomes avoided per 1000 (95% CI) 12 (9-16) 5 (1-8) 25 (19-31) 0 5 10 15 20 25 30 Coronary revascularisation StrokeMajor vascular events 0 5 10 15 25 30 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 (%)

13 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) 651671 (6·1)2344 (8·5)0·74 (0·69 – 0·79) >65 1666 (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) 90 2711 (7·8)3590 (10·3) 0·77 (0·73 – 0·81) >90 618 (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<0.0001 RR (95% CI) RR (99% CI) ≤ ≤

14 Groups Treatment Control Rate Ratio (CI) Total cholesterol (mmol/L) 5.2 748 (6·9)940 (8·6) 0·76 (0·66 – 0·88) 5.2-6.5 1678 (7·0)2246 (9·4) 0·76 (0·71 – 0·82) >6.5 896 (8·8)1220 (12·1) 0·78 (0·72 – 0·84) LDL cholesterol (mmol/L) 3.5 1130 (6·8)1443 (8·7) 0·76 (0·68 – 0·84) 3.5-4.5 1374 (7·3)1814 (9·6)0·77 (0·71 – 0·83) >4.5 801 (9·3)1120 (12·9) 0·78 (0·72 – 0·85) HDL cholesterol (mmol/L) 0.9 1167 (9·3)1538 (12·1)0·76 (0·70 – 0·84) 0.9-1.1 939 (7·4)1270 (10·2) 0·76 (0·70 – 0·83) >1.1 1207 (6·2)1595 (8·1) 0·77 (0·71 – 0·84) Triglycerides (mmol/L) 1.4 1162 (7·3)1521 (9·6) 0·78 (0·71 – 0·85) 1.4-2.0 937 (7·1) 1304 (9·8)0·77 (0·71 – 0·84) >2.0 1217 (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<0.0001 Effects on MAJOR CORONARY EVENTS per mmol/L LDL cholesterol reduction, subdivided by baseline prognostic factors (2) RR (95% CI) RR (99% CI) ≤ ≤ ≤ ≤

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