New Data Show High Adherence Rates with Pradaxa^® (dabigatran etexilate mesylate) in NVAF Patients

Ridgefield, CT, December 4, 2016 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced results from a new analysis of the GLORIA^™-AF Registry Program, which showed that newly diagnosed non-valvular atrial fibrillation (NVAF) patients treated with Pradaxa^® (dabigatran etexilate mesylate) had a 76.6 percent probability of remaining on treatment at one year and a 69.2 percent probability at two years. The results were presented today at the American Society of Hematology (ASH) Annual Meeting in San Diego, CA.

“Patients with NVAF are at a five times greater risk for stroke, and the goal of anticoagulant therapy is to reduce this risk. It is critical for patients and physicians to understand the benefits of staying on prescribed treatment and the potential risks of discontinuing,” said Jonathan Halperin, M.D., the Robert and Harriet Heilbrunn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, study author and member of the GLORIA-AF steering committee. “In general, nearly half of patients discontinue oral anticoagulant therapy after only a year, so it is promising to see high adherence rates with PRADAXA in this new analysis from the GLORIA-AF Registry.”

The analysis was based on real-world data from 2,937 PRADAXA patients receiving care at nearly 1,000 sites in 44 countries. Eighty-eight percent of the patients were considered at high risk for stroke (i.e., CHA₂DS₂-VASc score of 2 or higher), and many patients experienced other health conditions in addition to NVAF, including hypertension (78.9%), diabetes (22.7%) and heart failure (24.9%). Of patients who permanently discontinued treatment with PRADAXA, half (418/828) had switched to another oral anticoagulant by the second year of follow-up.

“Understanding how medicines are used in the real world, including factors that may influence patients to stop taking treatment, is essential to helping the community identify ways to improve patient outcomes,” said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “These results are encouraging and underscore that the majority of PRADAXA patients follow their treatment plan. The growing body of real-world data on PRADAXA, and the fact that it is the only novel oral anticoagulant with a specific reversal agent available, should offer healthcare providers, patients and caregivers added assurance in reducing stroke risk in NVAF patients.”

About GLORIA^™-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation)
GLORIA^™-AF is one of the largest worldwide registry programs to investigate the long-term use of oral antithrombotic therapies in reducing the risk of NVAF-related strokes in the clinical setting. The Registry examines physicians’ prescribing behaviors in treating NVAF, as well as the factors behind their prescribing decisions. The study is collecting long-term safety and effectiveness data on a range of antithrombotics, including warfarin, ASA (aspirin) and NOACs for stroke risk reduction in NVAF, as well as patient outcomes data.

The Registry Program will enroll up to 56,000 patients newly diagnosed with AF at risk of stroke from up to 2,200 sites in nearly 50 countries. 

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.

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with 146 affiliates and more than 47,000 employees. Since its founding in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel treatments for human and veterinary medicine.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and families. Our employees create and engage in programs that strengthen our communities. To learn more about how we make more health for more people, visit our Corporate Social Responsibility Report.

In 2015, Boehringer Ingelheim achieved net sales of about $15.8 billion (14.8 billion euros). R&D expenditure corresponds to 20.3 percent of its net sales.

For more information please visit https://www.boehringer-ingelheim.us/, or follow us on Twitter @BoehringerUS.  

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

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