New Data from Boehringer Ingelheim’s GLORIATM-AF Registry Show Non-Valvular Atrial Fibrillation (NVAF) Patients at High Risk of Stroke May Be Undertreated

• Data show initial therapy in newly diagnosed NVAF patients diverged from guideline recommendations

• Second analysis finds a proportion of NVAF patients at high risk of stroke are undertreated

• Data presented at American College of Cardiology Scientific Session (ACC.15)

Ridgefield, CT, March 16, 2015 –Boehringer Ingelheim Pharmaceuticals, Inc. today will present results from two analyses of the GLORIATM-AF Registry Program examining the use of antithrombotic treatment to reduce the risk of stroke for patients with non-valvular atrial fibrillation (NVAF). The new findings are the first reported prescribing patterns data from Phase II of the GLORIA-AF Registry Program and were included in poster presentation sessions at the American College of Cardiology 64th Annual Scientific Session.

“These real-world analyses highlight that while physicians have a variety of factors to consider when deciding on antithrombotic treatment options for NVAF patients, the fact remains that oral anticoagulants, the standard of care for significantly reducing the risk of stroke and systemic embolism in these patients, are underutilized,” said Jonathan L. Halperin, M.D., the Robert and Harriet Heilbrunn Professor of Medicine at Mount Sinai School of Medicine, lead author of the study, and member of the GLORIA-AF steering committee. “We need to continue to uncover why that is and what we can do to bridge that treatment gap.”

Results from one analysis demonstrated 21.9 percent of patients with paroxysmal (occasional) NVAF and a CHA2DS2-VASc score of 2 or higher were not given an oral anticoagulant medication*, compared to 12.4 percent and 11.2 percent of those diagnosed with persistent or permanent NVAF, respectively, and a CHA2DS2-VASc score of 2 or higher. Current NVAF guidelines call for a choice of antithrombotic therapy based on patients’ risk of stroke or thromboembolism and bleeding, rather than the type of NVAF.

A second analysis showed that a considerable number of new-onset NVAF patients with a CHA2DS2-VASc score of 2 or higher received aspirin alone or went untreated (age 64 or younger, 20.6 percent; age 65-74, 19.7 percent; age 75-79, 15.6 percent; age 80 or older, 17.6 percent). Newer drugs known as novel oral anticoagulants (NOACs) accounted for 52.1 percent of anticoagulants prescribed (25.0 percent dabigatran, 20.5 percent rivaroxaban, and 6.6 percent apixaban). The most frequently prescribed oral anticoagulants in patients with a CHA2DS2-VASc score of 2 or higher were vitamin K antagonists (VKAs, e.g., warfarin), especially among elderly and very elderly patients (age 64 or younger, 27.9 percent; age 65-74, 24.7 percent; age 75-79, 27.9 percent; age 80 or older, 31.7 percent).

“These examinations of the GLORIA-AF data suggest we still face challenges in ensuring patients receive guideline-recommended treatment to reduce their risk of stroke, which can be devastating or even fatal,” said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We believe these findings, as well as further analyses from the registry, will help to address needs in NVAF treatment.”

The data are based on treatment trends in 3,415 patients who entered the GLORIA-AF Registry from November 2011 to February 2014 in North America. All patients had a recent diagnosis of NVAF, and 86.2 percent had a CHA2DS2-VASc score of 2 or higher. NVAF accounts for up to 95 percent of AF cases in the U.S.

About the GLORIA-AF Registry Program
GLORIA-AF is a global Registry Program run in different phases and designed to characterize the population of newly diagnosed patients with NVAF at risk for stroke, and to study patterns, predictors and outcomes of different treatment regimens for stroke prevention. Patient characteristics, clinical usage patterns and patient outcomes of anticoagulation therapy will be documented in up to 56,000 patients in 2,200 sites and more than 50 countries throughout the world.

The current analyses are based on a pre-specified interim analysis which includes the baseline data from the first 10,000 patients enrolled in GLORIA-AF Phase II from five defined geographical regions.

About Pradaxa® (dabigatran etexilate mesylate) Capsules

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;
  • for the treatment of deep venous thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for 5-10 days;
  • to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in patients who have been previously treated

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.

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 for dabigatran is not available. Hemodialysis can remove dabigatran; however clinical experience for hemodialysis as a treatment for bleeding is limited.  Activated prothrombin complex concentrates, recombinant Factor VIIa, or concentrates of factors II, IX or X 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), consider reducing 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.

Treatment and Reduction in the Risk of Recurrence of DVT/PE

  • For patients with CrCl <50 mL/min, avoid use of PRADAXA and concomitant P-gp inhibitors

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

  • 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).

DVT/PE

  • Rates of any GI bleeds were higher in patients receiving PRADAXA 150 mg vs warfarin and placebo
  • In the active-controlled studies, there was a higher rate of clinical myocardial infarction (MI) in PRADAXA patients [20 (0.66/100) patient-years)] vs warfarin [5 (0.17/100 patient-years)].  In the placebo-controlled study, there was similar rate of non-fatal and fatal clinical MI in PRADAXA patients [1 (0.32/100 patient-years)] vs placebo [1 (0.34/100 patient-years)].
  • GI adverse reactions were similar in patients receiving PRADAXA 150 mg vs warfarin.  They were commonly dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) and gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis and gastric hemorrhage).

Drug hypersensitivity reactions were reported in ≤ 0.1% of patients receiving PRADAXA.

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.

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About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.

For more information please visit www.us.boehringer-ingelheim.com/

Pradaxa® and PRADAXA with associated design® are registered trademarks of Boehringer Ingelheim Pharma GmbH and Co. KG and used under license.

GLORIATM-AF is a trademark of Boehringer Ingelheim International GmbH and used under license.

 

   PR-PX-0004-PR 

Footnotes

*The analysis defined oral anticoagulation as vitamin K antagonists, dabigatran (Pradaxa® [dabigatran etexilate mesylate], Boehringer Ingelheim), rivaroxaban (Xarelto, Janssen), and apixaban (Eliquis, Bristol-Myers Squibb/Pfizer).