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Slide 1 - ASCOT Lancet, April 2003 n=10,305 Evidence for: primary prevention of CHD and stroke in high risk, middle aged, hypertensive, male patients with TC <6.5mmol/L Questions remaining: women n=1942; adverse & long term effects; safety and efficacy of titrating dose to attain targets & magnitude/$ 1o Prevention in high risk (Average 3.7 risk factors in addition to HTN) (HTN,male/female,age~63 40-79,TC<6.5mmol/L) Atorvastatin 10mg/d over average 3.3yrs NNT=91 NNT=143 NNT=NS Older males with multiple risk factors benefit.
Slide 2 - PROVE-ITNEJM, April, 2004 n=4,162 2yrs Atorvastatin 80mg/d $87 vs Pravastatin 40mg/d $42 After an Acute Coronary Syndrome (ACS) % patients Intensive vs moderate lipid lowering in high risk ACS pt LDL: 2.74 baseline mmol/L  1.60 atorv 80mg vs 2.46 pravastatin 40mg 1o end point “Death or CV Event”: all-cause mortality, MI, unstable angina, revascularization, and stroke Mean age ~58 over 2years NNT=NS NNT=26 (RRR=15%) NNH=46 Monitor for SE if using higher doses
Slide 3 - What about younger diabetics with no risk factors??
Slide 4 - TNTNEJM, April 2005 n=10,001 4.9yr Atorvastatin 80mg/d $87 vs 10mg/day $67 % patients Intensive lipid lowering in stable CHD (n=15,464 - 8wk run-in) LDL: 3.9 baseline mmol/L  2.0 atorv 80mg vs 2.6 atorv 10mg;Age 35-75, ~61 1o end point: “CHD Death, CV Event or Procedure, Stroke” CV & Stroke events; NNT=46 / 4.9yr; LFT's NNH=100; All-cause death  5.7 vs 5.6% BUT  non-CV death 3.2 vs 2.5 NS NNT=NS NNT=26 / 4.9yr (RRR=20%)  CV events;  ADRs; NO difference in all-cause death LFTs 3x NNH=100
Slide 5 - IDEALJAMA, Nov 2005 n=8888 4.8yr Atorvastatin 80mg/d $87 vs Simv 20-40mg/day $41 % patients Intensive lipid lowering in previous MI pts (open label trial) LDL: 3.14 baseline mmol/L 2.1 atorv 80mg vs 2.7 simv 20-40mg;Age<80, ~62 1o Primary: Coronary Death, nonfatal MI or cardiac resusc. 9.3 vs 10.4% NS 2o Major vascular events (1o & stroke) NNT=59/4.8yr;MI6 vs 7.2% NNT=84 LFT's NNH=112; All-cause death  8.2 vs 8.4% or CV death  5 vs4.9 but at least  non-CV death 3.2 vs 3.5 NS NNT=NS NNT=59 / 4.8yr (RRR=13%) LFTs 3x NNH=112  CV events;  ADRs; NO difference in all-cause death
Slide 6 - LDL Outcome Data Highest risk benefit most!
Slide 7 - page 55 NNT based on risk
Slide 8 - page 11 Statins best outcome evidence Age up to age 80 (HPS) Low risk women no/? benefit 20 benefit a lot; 10 small benefit