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Cholesterol Lowering and CV Risk: Meta-analyses

Cholesterol Lowering and CV Risk: Meta-analyses. On-Treatment LDL and CHD Events in Statin Trials. 30. 4S - PBO. Secondary Prevention. 4S - Rx. 20. LIPID - PBO. Event rate (%). CARE - PBO. LIPID - Rx. HPS - PBO. Primary Prevention. CARE - Rx. 10. HPS - Rx. TNT - ATV10.

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Cholesterol Lowering and CV Risk: Meta-analyses

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  1. Cholesterol Lowering and CV Risk: Meta-analyses

  2. On-Treatment LDL and CHD Events in Statin Trials 30 4S - PBO Secondary Prevention 4S - Rx 20 LIPID - PBO Event rate (%) CARE - PBO LIPID - Rx HPS - PBO Primary Prevention CARE - Rx 10 HPS - Rx TNT - ATV10 WOSCOPS - PBO TNT - ATV80 PROVE-IT - PRA AFCAPS - PBO PROVE-IT - ATV80 AFCAPS - Rx WOSCOPS - Rx WOSCOPS - Rx ASCOT - PBO ASCOT - Rx 0 40 (1.0) 60 (1.6) 70 (1.8) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) 200 (5.2) LDL-C achieved, mg/dL (mmol/L) Adapted from Rosenson RS. Expert Opin Emerg Drugs. 2004;9:269-279.LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.

  3. Second Cycle of the CTT Meta-analysis: Proportional Effects on Major VascularEvents Per Mmol/L LDL-C Reduction No. of events (% pa) Relative risk (CI) per mmol/L LDL-C reduction Statin/more Control/less More vs. less statin 406 (11.3) 458 (13.1) PROVE-IT 257 (7.2) 282 (8.1) A to Z 889 (4.0) 1164 (5.4) TNT 938 (5.2) 1106 (6.3) IDEAL 1347 (3.6) 1406 (3.8) SEARCH Subtotal (5 trials) 0.72 (0.66 - 0.78) P < 0.001 3837 (4.5) 4416 (5.3) Statin vs. control First cycle (14 trials) 5883 (3.1) 7467 (4.0) 0.78 (0.76 - 0.81) 254 (5.4) 293 (6.4) ALLIANCE 144 (9.0) 162 (10.1) 4D 114 (2.7) 136 (3.3) ASPEN 102 (0.5) 140 (0.7) MEGA 105 (0.5) 194 (1.0) JUPITER 172 (2.2) 174 (2.2) GISSI-HF 362 (8.1) 368 (8.3) AURORA 7136 (2.8) 8934 (3.6) Subtotal (21 trials) 0.79 (0.77 - 0.81) P < 0.001 Total (26 trials) 10973 (3.2) 13350 (4.0) 0.78 (0.76 - 0.80) P < 0.001 0.5 0.75 1 1.25 1.5 99% or 95% CI Statin/more better Control/less better Difference between more vs. less and statin vs. control: c 2 4.5, p=0.03 = 1 Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.

  4. Second Cycle of the CTT Meta-analysis:More vs Less Statin—Proportional Effects onMajor Vascular Events Per Mmol/L LDL-C Reduction No. of events (% pa) Relative risk (CI) per mmol/L LDL-C reduction More statin Less statin 1175 (1.3%) 1380 (1.5%) 0.71 (0.58 - 0.87) Nonfatal MI 645 (0.7%) 694 (0.7%) 0.85 (0.63 - 1.15) CHD death Any major coronary event 1725 (1.9%) 1973 (2.2%) 0.74 (0.65 - 0.85) P < 0.0001 637 (0.7%) 731 (0.9%) 0.72 (0.55 - 0.95) CABG 1166 (1.3%) 1508 (1.8%) 0.60 (0.50 - 0.71) PTCA Unspecified 447 (0.5%) 502 (0.6%) 0.78 (0.58 - 1.04) Any coronary revascularization 2250 (2.6%) 2741 (3.2%) 0.66 (0.60 - 0.73) P < 0.0001 440 (0.5%) 526 (0.6%) 0.69 (0.50 - 0.95) Ischemic stroke Hemorrhagic stroke 69 (0.1%) 57 (0.1%) 1.39 (0.57 - 3.39) 63 (0.1%) 80 (0.1%) 0.63 (0.24 - 1.66) Unknown stroke Any stroke 572 (0.6%) 663 (0.7%) 0.74 (0.59 - 0.92) P = 0.007 99% or 95% CI Any major vascular event (5 trials) 3837 (4.5%) 4416 (5.3%) 0.72 (0.66 - 0.78) 0.5 0.75 1 1.25 1.5 More statin better Less statin better Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.

  5. Second Cycle of the CTT Meta-analysis: Statinvs Control—Proportional Effects onMajor Vascular Events Per Mmol/L LDL-C Reduction No. of events (% pa) Relative risk (CI) per mmol/L LDL-C reduction Statin Control 2310 (0.9%) 3213 (1.2%) 0.74 (0.69 - 0.78) Nonfatal MI 1242 (0.5%) 1587 (0.6%) 0.80 (0.73 - 0.86) CHD death Any major coronary event 3380 (1.3%) 4539 (1.7%) 0.76 (0.73 - 0.79) P < 0.001 816 (0.3%) 1126 (0.4%) 0.76 (0.69 - 0.83) CABG 601 (0.2%) 775 (0.3%) 0.78 (0.69 - 0.89) PTCA Unspecified 1686 (0.6%) 2165 (0.8%) 0.76 (0.70 - 0.83) Any coronary revascularization 3103 (1.2%) 4066 (1.6%) 0.76 (0.73 - 0.80) P < 0.001 987 (0.4%) 1225 (0.5%) 0.80 (0.73 - 0.88) Ischemic stroke Hemorrhagic stroke 188 (0.1%) 163 (0.1%) 1.10 (0.86 - 1.42) 555 (0.2%) 629 (0.2%) 0.88 (0.76 - 1.02) Unknown stroke Any stroke 1730 (0.7%) 2017 (0.8%) 0.85 (0.80 - 0.90) P < 0.001 Any major vascular event (all 21 trials) 7136 (2.8%) 8934 (3.6%) 0.79 (0.77 - 0.81) P < 0.001 0.5 0.75 1 1.25 1.5 99% or 95% CI Statin better Control better Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681.

  6. Meta-analysis of Statin Trials and Fatal and Nonfatal Stroke N = 165,732 Active group (%) Control group (%) RR (95% CI) RR (95% CI) Study Primary prevention of stroke SEARCH JUPITER ASPEN MEGA IDEAL TNT ALLIANCE CARDS PROVE-IT A TO Z ASCOT-LLA ALLHAT-LLT GREACE HPS (with no prior CVD) PROSPER MIRACL GISSI AFCAPS/TexCAPS LIPID (with no prior CVD) Post-CABG CARE (with no prior CVD) WOSCOPS SSSS Sub-total:P < 0.0001 (heterogeneity: I2 = 26.6%, P = 0.12) 4.2 0.4 2.8 1.3 3.4 2.3 2.9 1.5 1.0 1.2 1.7 4.0 1.2 3.2 4.7 0.8 0.9 0.4 3.3 2.6 1.9 1.4 2.5 4.6 0.7 3.2 1.6 3.9 3.1 3.2 2.8 0.9 1.6 2.4 4.5 2.1 4.8 4.5 1.6 0.9 0.5 3.9 2.4 2.8 1.5 3.5 0.91 (0.77, 1.08) 0.52 (0.34, 0.78) 0.89 (0.56, 1.40) 0.83 (057,1.20) 0.87 (0.70, 1.08) 0.76 (0.60, 0.96) 0.90 (0.58, 1.42) 0.53 (0.31, 0.90) 1.09 (0.59, 2.01) 0.79 (0.48, 1.29) 0.73 (0.56, 0.96) 0.91 (0.76, 1.09) 0.53 (0.24, 1.18) 0.67 (0.57, 0.77) 1.04 (0.82, 1.31) 0.50 (0.25, 1.00) 1.05 (0.56, 1.96) 0.82 (0.41, 1.67) 0.84 (0.67, 1.05) 1.12 (0.58, 2.18) 0.67 (0.44, 1.01) 0.90 (0.61, 1.34) 0.72 (0.51, 1.01) 0.81 (0.75, 0.87) Secondary prevention of stroke SPARCL HPS (with prior CVD LIPID (with prior CVD) CARE (with prior CVD) Sub-total:P = 0.03 (heterogeneity: I2 = 0.8%, P = 0.39) 11.2 10.3 9.5 13.5 13.1 10.4 13.3 20.0 0.85 (0.73, 0.99 0.99 (0.81, 1.21) 0.72 (0.46, 1.12) 0.68 (0.37, 1.25) 0.88 (0.78, 0.99) 0.82 (0.77, 0.87 Total: P < 0.0001 (heterogeneity: I2 = 7.3%, P = 0.36) 0.1 0.2 0.5 1 2 5 10 Amarenco P et al. Lancet Neurol. 2009;8:453-463. Log-scale

  7. Meta-analysis of Statin Trials and Stroke Mortality Active group (%) Control group (%) RR (95% CI) RR (95% CI) Study Primary prevention of stroke SEARCH JUPITER CARDS ALLHAT-LLT GREACE HPS PROSPER MIRACL GISSI LIPID CARE WOSCOPS SSSS Sub-total:P = 0.18 (heterogeneity: I2 = 0%, P = 0.48) 0.9 0.3 0.1 1.0 0.0 0.9 0.8 0.2 0.2 0.5 0.2 0.2 0.6 1.1 0.7 0.5 1.1 0.1 1.2 0.5 0.1 0.2 0.6 0.1 0.1 0.5 0.85 (0.60, 1.21) 0.50 (0.13, 2.00) 0.14 (0.02, 1.15) 0.95 (0.65, 1.38) 0.33 (0.01, 8.17) 0.81 (0.62, 1.05) 1.58 (0.81, 3.09) 1.51 (0.25, 9.02) 1.00 (0.25, 3.98) 0.81 (0.46, 1.43) 4.99 (0.58, 42.70) 1.50 (0.42, 5.30) 1.17 (0.54, 2.52) 0.90 (0.76, 1.05) Secondary prevention of stroke SPARCL 1.0 1.7 0.59 (0.36, 0.97) Total: P = 0.10 (heterogeneity: I2 = 8.1%, P = 0.36) 0.87 (0.73, 1.03) 0.1 0.2 0.5 1 2 5 10 Log-scale Amarenco P et al. Lancet Neurol. 2009;8:453-463.

  8. Stroke Risk and LDL Lowering inStatin Trials Each 1 mmol (39 mg) LDL-C reduction reduced the risk of stroke by 21% (95% CI, 6.3–33.5%; p<0.009) 1.2 Post-CABG N = 165,732 PROVE-IT 1.1 GISSI PROSPER ALLHAT-LLT 1.0 SEARCH SPARCL-CS (-) WOSCOPS IDEAL 0.9 ASPEN LIPID ALLIANCE SPARCL AFCAPS/TexCAPS 0.8 MEGA A to Z Relative Risk of Stroke in Active vs Control Groups (non-log scale) ASCOT-LLA TNT HPS 0.7 SPARCL-CS (+) SSSS CARE 0.6 CARDS JUPITER 0.5 GREACE MIRACL 0.4 0 0 -10 -15 -20 -25 -30 -35 -40 -45 -50 -55 Between Group Difference in LDL-Cholesterol Reduction, % (active minus control groups) Amarenco P et al. Lancet Neurol. 2009;8:453-463.

  9. Second Cycle of the CTT Meta-analysis: Proportional Effects on Cause-SpecificMortality Per Mmol/L LDL-C Reduction No. of deaths(% pa) Relative risk (CI) per mmol/L LDL-C reduction Statin/more Control/less Vascular causes 1887 (0.5%) 2281 (0.6%) 0.80 (0.74 - 0.87) CHD 1446 (0.4%) 1603 (0.4%) 0.89 (0.81 - 0.98) Other cardiac 3333 (0.9%) 3884 (1.1%) 0.84 (0.80 - 0.88) All cardiac 153 (0.0%) 139 (0.0%) 1.04 (0.77 - 1.41) Ischemic stroke Hemorrhagic stroke 102 (0.0%) 89 (0.0%) 1.12 (0.77 - 1.62) 228 (0.1%) 273 (0.1%) 0.85 (0.66 - 1.08) Unknown stroke 483 (0.1%) 501 (0.1%) 0.96 (0.84 - 1.09) Stroke 404 (0.1%) 409 (0.1%) 0.98 (0.81 - 1.18) Other vascular Any vascular 4220 (1.2%) 4794 (1.3%) 0.86 (0.82 - 0.90) Nonvascular 1781 (0.5%) 1798 (0.5%) 0.99 (0.91 - 1.09) Cancer 224 (0.1%) 237 (0.1%) Respiratory 0.88 (0.70 - 1.11) 127 (0.0%) 127 (0.0%) 0.98 (0.70 - 1.38) Trauma 811 (0.2%) 832 (0.2%) 0.96 (0.83 - 1.10) Other nonvascular 2943 (0.8%) 2994 (0.8%) 0.97 (0.92 - 1.03) Any nonvascular 99% or 95% CI 479 (0.1%) 539 (0.1%) 0.87 (0.76 - 0.99) Unknown death Any death 7642 (2.1%) 8327 (2.3%) 0.90 (0.87 - 0.93) 0.5 0.75 1 1.25 1.5 Cholesterol Treatment Trialists Collaboration. Lancet. 2010;376:1670-1681. Control/less better Statin/more better

  10. Meta-analysis of Statin Trials: Effect ofIntensive LDL-C Lowering vs StandardStatin Therapy on Fatal and Nonfatal Stroke Intensive arm(%) Conventional arm (%) RR (95% CI) RR (95% CI) Study 4.2 3.4 2.3 2.9 1.0 1.2 4.6 3.9 3.1 3.2 0.9 1.6 0.91 (0.77, 1.08) 0.87 (0.70, 1.08) 0.76 (0.60, 0.96) 0.90 (0.58, 1.42) 1.09 (0.59, 2.01) 0.79 (0.48, 1.29) 0.87 (0.78, 0.96) SEARCH IDEAL TNT ALLIANCE PROVE-IT A to Z Total: P = 0.009 (heterogeneity: I2 = 0%, P = 0.80) 0.1 0.2 0.5 1 2 5 10 Log-scale Amarenco P et al. Lancet Neurol. 2009;8:453-463.

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