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/$ 1 o 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.

2. PROVE-IT NEJM, April, 2004 n=4,162 2yrs Atorvastatin 80mg/d $87 vs Pravastatin 40mg/d $42 After an Acute Coronary Syndrome (ACS) % patients% 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 1 o 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

3. What about younger diabetics with no risk factors??

4. TNT NEJM, April 2005 n=10,001 4.9yr Atorvastatin 80mg/d $87 vs 10mg/day $67 % patients% 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 1 o 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

5. IDEAL JAMA, Nov 2005 n=8888 4.8yr Atorvastatin 80mg/d $87 vs Simv 20-40mg/day $41 % patients% 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 1 o Primary : Coronary Death, nonfatal MI or cardiac resusc. 9.3 vs 10.4% NS 2 o Major vascular events ( 1 o & stroke) NNT=59/ 4.8yr ; MI 6 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

6. LDL Outcome Data Highest risk benefit most!

7. NNT based on risk

8. Statins best outcome evidence Age up to age 80 (HPS) Low risk women no/? benefit 2 0 benefit a lot; 1 0 small benefit