Atorvastatin for Reduction of Myocardial Dysrhythmias After Cardiac Surgery Trial Presented at The American College of Cardiology Scientific Sessions March 2006 Presented by Dr. Giuseppe Patti ARMYDA-3 Trial

www. Clinical trial results.org ARMYDA-3 Trial: Background The objective of this trial was to evaluate the effects of treatment with atorvastatin versus placebo on the occurrence of post- operative atrial fibrillation among patients undergoing elective cardiac surgeryThe objective of this trial was to evaluate the effects of treatment with atorvastatin versus placebo on the occurrence of post- operative atrial fibrillation among patients undergoing elective cardiac surgery Statin therapy has been shown to be associated with reductions in ischemic events following acute coronary syndromesStatin therapy has been shown to be associated with reductions in ischemic events following acute coronary syndromes It is hypothesized that statin therapy will reduce incidences of post- operative atrial fibrillation because of its anti-inflammatory effectsIt is hypothesized that statin therapy will reduce incidences of post- operative atrial fibrillation because of its anti-inflammatory effects The objective of this trial was to evaluate the effects of treatment with atorvastatin versus placebo on the occurrence of post- operative atrial fibrillation among patients undergoing elective cardiac surgeryThe objective of this trial was to evaluate the effects of treatment with atorvastatin versus placebo on the occurrence of post- operative atrial fibrillation among patients undergoing elective cardiac surgery Statin therapy has been shown to be associated with reductions in ischemic events following acute coronary syndromesStatin therapy has been shown to be associated with reductions in ischemic events following acute coronary syndromes It is hypothesized that statin therapy will reduce incidences of post- operative atrial fibrillation because of its anti-inflammatory effectsIt is hypothesized that statin therapy will reduce incidences of post- operative atrial fibrillation because of its anti-inflammatory effects Presented at ACC 2006

www. Clinical trial results.org ARMYDA-3 Trial: Study Design Presented at ACC 2006  Primary Endpoint: Post-operative occurrence of atrial fibrillation lasting >5 minutes through discharge Atorvastatin 40 mg/day n=101 Atorvastatin 40 mg/day n=101 Placebo n=99 Placebo n= patientsundergoing elective cardiac surgery were randomized to either atorvastatin or placebobeginning 7 days before the operation 200 patients undergoing elective cardiac surgery were randomized to either atorvastatin or placebo beginning 7 days before the operation Placebo-controlled. Randomized. Blinded 31% female, mean age 66 years, mean follow-up 30 days Patients had no previous history of statin treatment or atrial fibrillation Baseline EF was 52%; 97% of patients had multi-vessel disease 200 patientsundergoing elective cardiac surgery were randomized to either atorvastatin or placebobeginning 7 days before the operation 200 patients undergoing elective cardiac surgery were randomized to either atorvastatin or placebo beginning 7 days before the operation Placebo-controlled. Randomized. Blinded 31% female, mean age 66 years, mean follow-up 30 days Patients had no previous history of statin treatment or atrial fibrillation Baseline EF was 52%; 97% of patients had multi-vessel disease C-reactive protein (CRP) levels measured prior to surgery and every 24 hours until discharge

www. Clinical trial results.org ARMYDA-3 Trial: Primary Endpoint Post-operative occurrence of atrial fibrillation occurred less frequently in the atorvastatin group than in the placebo group (35% vs 57%; p=0.003)Post-operative occurrence of atrial fibrillation occurred less frequently in the atorvastatin group than in the placebo group (35% vs 57%; p=0.003) Post-operative occurrence of atrial fibrillation (%) p=0.003 % occurrence AF Presented at ACC 2006

www. Clinical trial results.org ARMYDA-3 Trial: Clinical Results ARMYDA-3 Trial: Clinical Results Presented at ACC 2006 Duration of hospitalization was shorter in the atorvastatin group than in the placebo group (6.3 vs 6.9 days; p=0.001)Duration of hospitalization was shorter in the atorvastatin group than in the placebo group (6.3 vs 6.9 days; p=0.001) Mean Duration of Hospitalization (days) p=0.001

www. Clinical trial results.org ARMYDA-3 Trial: Clinical Results Presented at ACC 2006 Time of onset of atrial fibrillation from surgery (Hours) p=NS Duration of arrhythmic episodes (Hours) p=NS There was no difference in time of onset of atrial fibrillation from surgery or duration of arrhythmic episodes There was no difference in time of onset of atrial fibrillation from surgery or duration of arrhythmic episodes Through 30 days there were 2 deaths in each group, 3 MIs in each group, no repeat revascularizations, and 1 stroke in the placebo group Through 30 days there were 2 deaths in each group, 3 MIs in each group, no repeat revascularizations, and 1 stroke in the placebo group

www. Clinical trial results.org ARMYDA-3 Trial: Limitations The rate of post-operative fibrillation was relatively high due to the definition of the event which only required 5 minutes of atrial fibrillation to meet the endpoint criteriaThe rate of post-operative fibrillation was relatively high due to the definition of the event which only required 5 minutes of atrial fibrillation to meet the endpoint criteria A larger study would be needed to confirm these findingsA larger study would be needed to confirm these findings The rate of post-operative fibrillation was relatively high due to the definition of the event which only required 5 minutes of atrial fibrillation to meet the endpoint criteriaThe rate of post-operative fibrillation was relatively high due to the definition of the event which only required 5 minutes of atrial fibrillation to meet the endpoint criteria A larger study would be needed to confirm these findingsA larger study would be needed to confirm these findings Presented at ACC 2006

www. Clinical trial results.org ARMYDA-3 Trial: Summary Treatment with atorvastatin was associated with a reduction in the occurrence of post-operative atrial fibrillation compared with placebo in patients undergoing elective cardiac surgeryTreatment with atorvastatin was associated with a reduction in the occurrence of post-operative atrial fibrillation compared with placebo in patients undergoing elective cardiac surgery Patients in the atorvastatin group had a significantly shorter duration of hospitalization (6.3 days vs 6.9 days, p=0.001) but no difference was seen between the groups in time of onset of atrial fibrillation or duration of arrhythmic episodesPatients in the atorvastatin group had a significantly shorter duration of hospitalization (6.3 days vs 6.9 days, p=0.001) but no difference was seen between the groups in time of onset of atrial fibrillation or duration of arrhythmic episodes Peak post-operative CRP levels were significantly lower in patients without atrial fibrillation than in patients with atrial fibrillation (p<0.025) regardless of study drug randomization groupPeak post-operative CRP levels were significantly lower in patients without atrial fibrillation than in patients with atrial fibrillation (p<0.025) regardless of study drug randomization group Treatment with atorvastatin was associated with a reduction in the occurrence of post-operative atrial fibrillation compared with placebo in patients undergoing elective cardiac surgeryTreatment with atorvastatin was associated with a reduction in the occurrence of post-operative atrial fibrillation compared with placebo in patients undergoing elective cardiac surgery Patients in the atorvastatin group had a significantly shorter duration of hospitalization (6.3 days vs 6.9 days, p=0.001) but no difference was seen between the groups in time of onset of atrial fibrillation or duration of arrhythmic episodesPatients in the atorvastatin group had a significantly shorter duration of hospitalization (6.3 days vs 6.9 days, p=0.001) but no difference was seen between the groups in time of onset of atrial fibrillation or duration of arrhythmic episodes Peak post-operative CRP levels were significantly lower in patients without atrial fibrillation than in patients with atrial fibrillation (p<0.025) regardless of study drug randomization groupPeak post-operative CRP levels were significantly lower in patients without atrial fibrillation than in patients with atrial fibrillation (p<0.025) regardless of study drug randomization group Presented at ACC 2006