AGGRENOX TM Safety Head, Drug Surveillance and Information Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, Connecticut Kenneth Rakowski, MD

Are there any particular safety concerns with the use of AGGRENOX TM ?

Safety Profile of AGGRENOX TM Summary No unexpected adverse effects No unexpected adverse effects Expected adverse effects are established for the two components Expected adverse effects are established for the two components Benefit/risk is favorable Benefit/risk is favorable

Central & Peripheral Nervous System Disorders Headache Gastro-Intestinal System Disorders Dyspepsia Abdominal pain Nausea Diarrhea Vomiting Melena Platelet, Bleeding & Clotting Disorders Hemorrhage NOS Purpura Red Blood Cell Disorders Anemia Placebo DP AloneASA Alone AGGRENOX™ Body System/Preferred Term (%)(%)(%)(%) Placebo DP AloneASA Alone AGGRENOX™ Body System/Preferred Term (%)(%)(%)(%) On-Treatment Adverse Events With an Incidence in the AGGRENOX TM Group Exceeding That in the Placebo Group by 1% or More Individual Treatment Group Total No. of Patients Total No. of Patients With  1 AE1304(79.1) 1305(78.9)1323(80.2)1319(79.9)

Incidence of Most Common Adverse Events Associated With Treatment Cessation Treatment Groups Total Number of Patients Patients With at Least One AE Associated With Treatment Cessation Headache Dizziness4 645 Nausea3 636 Abdominal pain3 434 Dyspepsia3 434 Vomiting1 323 Diarrhea<12<12 Stroke4 332 Transient ischemic attack3222 Angina pectoris21<11 Myocardial infarction1<1<1<1 PlaceboDPASAAGGRENOX™ %% PlaceboDPASAAGGRENOX™ %%

Potential Interactions Drug-Disease No clinically significant differences No clinically significant differencesDrug-Demographics

Laboratory Analyses No clinically significant effects in any group No clinically significant effects in any group Hematology, indices of kidney function, presence of abnormal or normal liver function, fasting glucose, total cholesterol, LDL cholesterol assessed Hematology, indices of kidney function, presence of abnormal or normal liver function, fasting glucose, total cholesterol, LDL cholesterol assessed

Headaches<0.001 Gastro-Intestinal Events<0.001 Nausea0.009 Diarrhea<0.001<0.001 Vomiting0.027 Bleeding Events<0.001 Ulcers0.059 Common Adverse Events of DP and ASA Confirmed by Factorial Analysis Body System/DP Main ASA Preferred TermEffectEffect Factorial Analysis Significant P-Values

Incidence of On-Treatment Adverse Events (  1%) Bleeding Events and Ulcers Total No. of Patients Total No. of Patients 1304(79.1) 1305(78.9)1323(80.2)1319(79.9) With  1 Adverse Event Bleeding Events92(6) 94(6) 160(10)171(10) Epistaxis 25(1.5) 16(1.0) 45(2.7)39(2.4) Purpura 7(0.4) 8(0.5)9(0.5)23(1.4) Melena 13(0.8) 10(0.6)20(1.2)31(1.9) GI hemorrhage 7(0.4) 5(0.3)15(0.9)20(1.2) Rectal hemorrhage 13(0.8)22(1.3)16(1.0)26(1.6) Hemorrhage NOS 24(1.5) 24(1.5)46(2.8)52(3.2) Hematuria 8(0.5) 13(0.8)26(1.6)11(0.7) Ulcers14(0.8) 10(0.6)20(1.2)19(1) PlaceboDPASAAGGRENOX TM (%) (%)Alone (%)(%) Treatment Group

Incidence of On-Treatment Serious Adverse Events Bleeding Events and Ulcers Intracranial Hemorrhage5444 Bleeding Events Melena41511 Gastrointestinal hemorrhage1127 Rectal hemorrhage1113 Hemorrhage NOS0123 Hematuria0233 Hematemesis5243 Gastro-Intestinal Ulcer2357 PlaceboDPASAAGGRENOX TM (%)(%)Alone (%)Alone (%) Treatment Group Total No. of Patients Total No. of Patients 560 (34)467 (28)529 (32)454 (28) With  1 SAE

On-Treatment Deaths Bleeding Events and Ulcers PlaceboDPASAAGGRENOX™ (%)(%)(%)(%) Treatment Group Total No. of Patients Total Deaths135 (8)124 (7)125 (8)107 (6) Ulcers or Bleeds2105

Safety Conclusions ESPS-2 clinical data supports the safety of AGGRENOX™ ESPS-2 clinical data supports the safety of AGGRENOX™ No unexpected adverse events observed with combined use of DP and ASA No unexpected adverse events observed with combined use of DP and ASA

Safety Conclusions DP-related adverse events are primarily headache and gastrointestinal complaints, as expected DP-related adverse events are primarily headache and gastrointestinal complaints, as expected ASA-related adverse events are primarily bleeding events, as expected ASA-related adverse events are primarily bleeding events, as expected

Safety Conclusions Serious adverse events of potential clinical significance other than stroke were uncommon Serious adverse events of potential clinical significance other than stroke were uncommon No demographic or disease-related factors identified No demographic or disease-related factors identified Data demonstrate the safety of AGGRENOX™ when taken as directed Data demonstrate the safety of AGGRENOX™ when taken as directed Benefit-risk of AGGRENOX™ is favorable Benefit-risk of AGGRENOX™ is favorable