New Real-World Data Show Pradaxa® (dabigatran etexilate mesylate) Treatment Resulted in Less Use of All-Cause Healthcare Resources than Warfarin Treatment

-- Nearly 4,000 newly treated non-valvular atrial fibrillation patients included

-- Findings published in The American Journal of Pharmacy Benefits

NEWS PROVIDED BY
Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc. today announced that The American Journal of Pharmacy Benefits (AJPB) published results from a real-world analysis comparing healthcare resource utilization data among nearly 4,000 recently diagnosed non-valvular atrial fibrillation (NVAF) patients newly treated with Pradaxa® (dabigatran etexilate mesylate) or warfarin. The analysis shows that patients treated with PRADAXA experienced fewer all-cause annual hospitalizations, emergency room (ER) visits and physician office visits, than those treated with warfarin.

"While there are many published studies comparing the clinical outcomes of PRADAXA and warfarin, this is one of the first to compare their respective impact on the use of healthcare resources," said Matthew Sussman, MA, lead author of the study and Associate Managing Director of Boston Health Economics, Inc. "Beyond data from clinical studies, it is important for physicians to also understand the experiences patients have in real-world settings, including the economic considerations of their treatment choices."

Data on 3,890 NVAF patients (1,945 newly treated with PRADAXA and 1,945 newly treated with warfarin) were analyzed using de-identified electronic health records from a large, nationwide database of U.S. integrated delivery networks (IDNs). Patients in the warfarin cohort were propensity-score matched 1:1 to patients in the PRADAXA cohort and were followed up to one year after initiating therapy to assess all-cause, stroke-related, and bleed-related healthcare resource use.

The results showed that patients treated with PRADAXA had significantly lower (42.8% vs. 47.5%; P=0.007) all-cause hospitalization than their warfarin counterparts. Additional analyses demonstrated a significantly lower number of per-patient per-year (PPPY) hospitalizations (1.07 vs. 1.20), ER visits (0.36 vs. 0.51) and physician office visits (10.64 vs. 18.13), compared to those treated with warfarin. Additionally, PRADAXA patients had a significantly lower PPPY total number of stroke-related hospitalizations (0.06 vs. 0.10) and physician office visits (0.16 vs. 0.29) as well as bleed-related ER visits (0.01 vs. 0.03), than those treated with warfarin.

"At Boehringer Ingelheim, we strongly believe that real-world data are critical in order to better understand the potential of our therapies in helping improve patient outcomes and facilitating efficient use of healthcare resources," said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We believe this analysis is an important complement to our clinical trial program, in which PRADAXA demonstrated superior efficacy and a favorable risk-benefit profile compared to warfarin, and additionally to support other real-world analyses of NVAF patients."

About Pradaxa® (dabigatran etexilate mesylate)

Indications and Usage
Pradaxa® (dabigatran etexilate mesylate) capsules is indicated:

to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation

IMPORTANT SAFETY INFORMATION ABOUT PRADAXA
WARNING: (A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA
(A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF THROMBOTIC EVENTS
Premature discontinuation of any oral anticoagulant, including PRADAXA, increases the risk of thrombotic events. If anticoagulation with PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant
(B) SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas may occur in patients treated with PRADAXA who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

use of indwelling epidural catheters
concomitant use of other drugs that affect hemostasis, such as non-steroidal
anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
a history of traumatic or repeated epidural or spinal punctures
a history of spinal deformity or spinal surgery
optimal timing between the administration of PRADAXA and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients who are or will be anticoagulated.

CONTRAINDICATIONS
PRADAXA is contraindicated in patients with:
- active pathological bleeding;
- known serious hypersensitivity reaction (e.g., anaphylactic reaction or anaphylactic shock) to PRADAXA;
- mechanical prosthetic heart valve

WARNINGS & PRECAUTIONS
Increased Risk of Thrombotic Events after Premature Discontinuation
Premature discontinuation of any oral anticoagulant, including PRADAXA, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. If PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant and restart PRADAXA as soon as medically appropriate.

Risk of Bleeding

PRADAXA increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss (e.g., a drop in hemoglobin and/or hematocrit or hypotension). Discontinue PRADAXA in patients with active pathological bleeding.
Risk factors for bleeding include concomitant use of medications that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA's anticoagulant activity and half-life are increased in patients with renal impairment.
Reversal of Anticoagulant Effect: A specific reversal agent (idarucizumab) for dabigatran is available when reversal of the anticoagulant effect of dabigatran is needed:
- For emergency surgery/urgent procedures
- In life-threatening or uncontrolled bleeding

Hemodialysis can remove dabigatran; however clinical experience for hemodialysis as a treatment for bleeding is limited. Prothrombin complex concentrates or recombinant Factor VIIa may be considered but their use has not been evaluated. Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity. Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used.

Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves
The use of PRADAXA is contraindicated in patients with mechanical prosthetic valves due to a higher risk for thromboembolic events, especially in the post-operative period, and an excess of major bleeding for PRADAXA vs. warfarin. Use of PRADAXA for the prophylaxis of thromboembolic events in patients with AFib in the setting of other forms of valvular heart disease, including bioprosthetic heart valve, has not been studied and is not recommended.

Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure
Concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided. P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.

Reduction of Risk of Stroke/Systemic Embolism in NVAF

For patients with moderate renal impairment (CrCl 30-50 mL/min), reduce the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA.
For patients with severe renal impairment (CrCl 15-30 mL/min), avoid concomitant use of PRADAXA and P-gp inhibitors.

ADVERSE REACTIONS
The most serious adverse reactions reported with PRADAXA were related to bleeding.

Most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding & gastrointestinal (GI) events.
PRADAXA 150 mg resulted in higher rates of major and any GI bleeds compared to warfarin.
In patients ≥75 years of age, the risk of major bleeding may be greater with PRADAXA vs warfarin.
Patients on PRADAXA 150 mg had an increased incidence of GI adverse reactions. These were commonly dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) and gastritis-like symptoms (including GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, and GI ulcer)

Other Measures Evaluated
In NVAF patients, a higher rate of clinical MI was reported in patients who received PRADAXA (0.7/100 patient-years for 150 mg dose) than in those who received warfarin (0.6).
Please see full Prescribing Information, including boxed WARNING and Medication Guide.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

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Boehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the trademark Pradaxa® under license.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.