PROVEN SAFETY IN DVT AND PE VS. WARFARIN

In 2 clinical trials for the treatment of DVT and PE, PRADAXA demonstrated lower rates of total bleeds vs. warfarin*¹

Bleeding Events in RE-COVER® and RE‑COVER II^™1

Full Treatment Period Including Parenteral Treatment

Event	PRADAXA 150 mg BID  % (n=2553)	warfarin % (n=2554)	HR (95% CI)
Major Bleeding†	1.4 (37/2553)	2.0 (51/2554)	0.73 (0.48, 1.11)
Clinically relevant nonmajor bleeding	4.0 (101/2553)	6.7 (170/2554)	0.58 (0.46, 0.75)
Total bleeds	16.1 (411/2553)	22.7 (567/2554)	0.70 (0.61, 0.79)

Rate of total GI bleeds in full treatment period was 3.1% for PRADAXA vs. 2.4% for warfarin¹

In a clinical trial for the reduction in the risk of recurrence of DVT and PE, PRADAXA demonstrated a higher rate of total bleeds vs. placebo^§1

Bleeding Events in RE‑SONATE®¹

Event	PRADAXA 150 mg BID % (n=684)	Placebo % (n=659)	HR (95% CI)
Major Bleeding†	0.3 (2/684)	0
Clinically relevant nonmajor bleeding	5.0 (34/684)	2.0 (13/659)	2.54 (1.34, 4.82)
Total bleeds	10.5 (72/684)	6.1 (40/659)	1.77 (1.20, 2.61)

Rate of total GI bleeds in treatment period was 0.7% for PRADAXA vs. 0.3% for placebo¹

ADVERSE REACTIONS IN CLINICAL TRIALS

The most serious adverse reactions reported with PRADAXA were related to bleeding¹

Drug discontinuation

• The rates of adverse reactions leading to treatment discontinuation were 21% for PRADAXA 150 mg and 16% for warfarin in the RE‑LY^® Trial¹

• The most frequent adverse reactions leading to discontinuation of PRADAXA in the RE‑LY^® Trial were bleeding and GI events (i.e., dyspepsia, nausea, upper abdominal pain, GI hemorrhage, and diarrhea)¹

Clinical MI events¹

• In the active-controlled DVT/PE studies, a higher rate of clinical MI was reported in patients who received PRADAXA [20 events (0.66 per 100 patient-years)] than in those who received warfarin [5 events (0.17 per 100 patient-years)]

• In the placebo-controlled DVT/PE study, a similar rate of non-fatal and fatal clinical MI was reported in patients who received PRADAXA [1 event (0.32 per 100 patient-years)] and in those who received placebo [1 event (0.34 per 100 patient-years)]

• In the DVT/PE after hip replacement studies, clinical MI was reported in 2 (0.1%) patients who received PRADAXA 220 mg and 6 (0.3%) patients who received enoxaparin

Gastrointestinal adverse reactions¹

In the RE‑LY^® Trial, increased incidence of GI adverse reactions (35% on PRADAXA vs. 24% on warfarin) were:

• Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort)

• Gastritis-like symptoms (including GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, and GI ulcer)

In the 4 pivotal DVT/PE studies, similar incidence of GI adverse reactions (24.7% on PRADAXA vs. 22.7% on warfarin) were:

• Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort), which occurred in 7.5% on PRADAXA vs. 5.5% on warfarin

• Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis, and gastric hemorrhage), which occurred in 3.0% on PRADAXA vs. 1.7% on warfarin

In the DVT/PE after hip replacement studies, the rate of major GI bleeds in patients receiving PRADAXA 220 mg and enoxaparin was the same; rate of any GI bleeds was higher in patients receiving PRADAXA 220 mg vs. enoxaparin. GI adverse reactions were the same in patients receiving PRADAXA 220 mg vs. enoxaparin. These were:

• Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort)

• Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis and gastric hemorrhage)

Hypersensitivity reactions¹

• In the RE‑LY^® Trial, drug hypersensitivity (including urticaria, rash, and pruritus), allergic edema, anaphylactic reaction, and anaphylactic shock were reported in <0.1% of patients receiving PRADAXA

• In the 4 pivotal DVT/PE studies, drug hypersensitivity (including urticaria, rash, and pruritus), allergic edema, anaphylactic reaction, and anaphylactic shock were reported in 0.1% of patients receiving PRADAXA

• In the DVT/PE after hip replacement studies, drug hypersensitivity (such as urticaria, rash, and pruritus) was reported in 0.3% of patients receiving PRADAXA 220 mg