Treating to New Targets Study TNT Trial Presented at The American College of Cardiology Scientific Sessions 2005 Presented by Dr. John C. LaRosa

www. Clinical trial results.org Atorvastatin 80 mg n=4,995 Atorvastatin 80 mg n=4,995 Primary Endpoint: Major cardiovascular event defined as coronary heart death (CHD), nonfatal M, resuscitated cardiac arrest, and fatal or nonfatal stroke at a mean follow-up of 4.9 years. Secondary Endpoint: Major coronary events, cerebrovascular events, hospitalization for congestive heart failure (CHF), all-cause mortality, peripheral artery disease, any cardiovascular event, any coronary event Primary Endpoint: Major cardiovascular event defined as coronary heart death (CHD), nonfatal M, resuscitated cardiac arrest, and fatal or nonfatal stroke at a mean follow-up of 4.9 years. Secondary Endpoint: Major coronary events, cerebrovascular events, hospitalization for congestive heart failure (CHF), all-cause mortality, peripheral artery disease, any cardiovascular event, any coronary event TNT Trial Presented at ACC 2005 Atorvastatin 10 mg n=5,006 Atorvastatin 10 mg n=5,006 10,003 patients with stable coronary heart disease Age years, LDL between 130 and 250 mg/dL, triglyceride ≤ 600 mg/dL 19% female, mean age 60.3 years All received atorvastatin 10 mg during 8 week open-label run-in period 10,003 patients with stable coronary heart disease Age years, LDL between 130 and 250 mg/dL, triglyceride ≤ 600 mg/dL 19% female, mean age 60.3 years All received atorvastatin 10 mg during 8 week open-label run-in period

www. Clinical trial results.org TNT Trial: Primary endpoint The primary composite endpoint of CHD death, nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke was lower in the high-dose atorvastatin 80 mg group at a mean follow-up of 4.9 years. Primary Composite of CHD death, nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke Hazard Ratio [HR]=0.78 p<0.001 Presented at ACC 2005

www. Clinical trial results.org TNT Trial: Primary Endpoint p=0.09 p=0.004 p=0.89 p=0.02 The individual components of the primary endpoint were also lower or tended to be lower in the high-dose group compared to the low-dose group with the exception of resuscitation after cardiac arrest, which was the equal in both groups. Presented at ACC 2005

www. Clinical trial results.org TNT Trial: Secondary Endpoint The components of the secondary endpoint that were lower in the high-dose group included: major coronary events, cerebrovascular events, and hospitalization for CHF. All-cause mortality and peripheral artery disease were equivalent in both high and low dose groups. Cerebrovascular Events p=0.007 Major Coronary Events p=0.002 CHF p=0.01 All-cause Mortality p=0.92 Peripheral Artery Disease p=0.76 Presented at ACC 2005

www. Clinical trial results.org TNT Trial p<0.001 Presented at ACC 2005 Persistent elevations in liver aminotransferase levels, treatment-related adverse events, and study drug discontinuation due to adverse events were all higher in the high-dose group compared to the low-dose group. p<0.001

www. Clinical trial results.org TNT Trial: Summary Among patients with stable coronary heart disease treatment with high-dose atorvastatin to achieve an LDL below 100 mg/dL was associated with a reduction in the primary composite endpoint of major cardiovascular events at 5 years compared with treatment with low- dose atorvastatin to achieve an LDL of approximately 100 mg/dL. Among patients with stable coronary heart disease treatment with high-dose atorvastatin to achieve an LDL below 100 mg/dL was associated with a reduction in the primary composite endpoint of major cardiovascular events at 5 years compared with treatment with low- dose atorvastatin to achieve an LDL of approximately 100 mg/dL. There was no difference in all-cause mortality in the high-dose compared to the low-dose group. There was no difference in all-cause mortality in the high-dose compared to the low-dose group. Persistent elevations in liver aminotransferase, treatment-related adverse events, and study drug discontinuation all occurred more frequently in the high-dose atorvastatin group compared to the low- dose group. There was no difference by treatment group in persistent CK elevations, myalgia, or rhabdomyolysis. Persistent elevations in liver aminotransferase, treatment-related adverse events, and study drug discontinuation all occurred more frequently in the high-dose atorvastatin group compared to the low- dose group. There was no difference by treatment group in persistent CK elevations, myalgia, or rhabdomyolysis. Presented at ACC 2005

www. Clinical trial results.org TNT Trial: Summary cont’d The overall safety profile was consistent with other large atorvastatin trials, and was likely relatively low due to the exclusion of the 131 patients with abnormal liver-function tests or myalgia during the run-in phase. Despite the exclusion of these patients, persistent with abnormal liver-function tests were more frequent with the 80 mg atorvastatin group, suggesting close monitoring is warranted in pateints treated with this dose.The overall safety profile was consistent with other large atorvastatin trials, and was likely relatively low due to the exclusion of the 131 patients with abnormal liver-function tests or myalgia during the run-in phase. Despite the exclusion of these patients, persistent with abnormal liver-function tests were more frequent with the 80 mg atorvastatin group, suggesting close monitoring is warranted in pateints treated with this dose. In the PROVE-IT / TIMI 22 trial, aggressive lipid lowering with atorvastatin 80 mg was associated with a reduction in cardiovascular events compared with standard LDL lowering with pravastatin in patients with acute coronary syndrome.In the PROVE-IT / TIMI 22 trial, aggressive lipid lowering with atorvastatin 80 mg was associated with a reduction in cardiovascular events compared with standard LDL lowering with pravastatin in patients with acute coronary syndrome. The results from TNT confirm what was observed in PROVE-IT / TIMI 22 and suggest that aggressive lipid lowering to LDL levels <75 mg/dL reduces cardiovascular events in patients with stable coronary artery disease.The results from TNT confirm what was observed in PROVE-IT / TIMI 22 and suggest that aggressive lipid lowering to LDL levels <75 mg/dL reduces cardiovascular events in patients with stable coronary artery disease. Presented at ACC 2005