RE-DUAL PCI™ Results Offer Favorable New Safety Data on Pradaxa®

RIDGEFIELD, Conn., Aug. 27, 2017 /PRNewswire/ -- Boehringer Ingelheim today announced that the RE-DUAL PCI™ trial evaluating Pradaxa® (dabigatran etexilate mesylate) dual therapy for people with non-valvular atrial fibrillation who have undergone percutaneous coronary intervention (PCI) with stenting met its primary endpoint, showing favorable new safety data on Pradaxa. The findings were presented today at a late-breaking spotlight session at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain and simultaneously published in the New England Journal of Medicine.

PCI, also known as angioplasty, is a medical intervention where stents may be used when widening arteries of the heart in patients with coronary artery disease. This intervention is conducted to restore or improve blood flow to the heart muscle.

"As many as 30 percent of people with atrial fibrillation have coronary artery disease that may require percutaneous coronary intervention with stenting. Before now, there has been limited research on the use of novel oral anticoagulants (NOACs) in this setting," said Christopher Cannon, MD, cardiologist at Brigham and Women's Hospital, lead investigator of RE-DUAL PCI, and executive director of the Cardiometabolic Trials at the Baim Institute for Clinical Research. "Because a rising number of these patients are already on NOAC treatment – we believe these results will provide important new insights for healthcare providers performing this procedure."  

The RE-DUAL PCI trial compared dual therapy with triple therapy after PCI with stent placement in approximately 2,500 adults with atrial fibrillation. Patients were either treated with Pradaxa and a single antiplatelet agent or with the vitamin K antagonist warfarin and two antiplatelets. The primary safety endpoint of the trial was defined by time to major bleeding events and clinically-relevant non-major bleeding events, when compared to triple therapy with warfarin.

"We believe that these results from the RE-DUAL PCI trial add to the growing body of evidence on Pradaxa and may help fill an unmet clinical need," said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "The safety and efficacy of Pradaxa have been well-established through one of the largest stroke prevention trials, and it has the longest real-world experience of any available NOAC."

To learn more about results from the RE-DUAL PCI trial, please refer to the publication in the New England Journal of Medicine.

About RE-DUAL PCI™
RE-DUAL PCI (NCT02164864) evaluates dual therapy with dabigatran etexilate mesylate vs. triple therapy with warfarin in atrial fibrillation patients who have undergone PCI with stenting.

RE-DUAL PCI has randomized 2,727 adult patients who have undergone PCI with stenting (elective or due to an acute coronary syndrome) at 550 sites in over 40 countries worldwide.

The main objective of the study is to compare a dual antithrombotic therapy regimen of either 150mg or 110mg dabigatran etexilate mesylate twice daily plus clopidogrel or ticagrelor versus a triple antithrombotic therapy combination of warfarin plus clopidogrel or ticagrelor plus aspirin <= 100mg once daily.

The primary safety endpoint of the 30 month study is the time to first major bleeding event, as defined by the International Society on Thrombosis and Haemostasis (ISTH), or clinically relevant non-major bleeding event. The secondary outcome measures include composite efficacy endpoints of time to death or first thrombotic event (all death, myocardial infarction, stroke or systemic embolism) and unplanned revascularization.

About Percutaneous Coronary Intervention (PCI)
Patients with atrial fibrillation who undergo PCI with stenting are at increased risk of serious complications caused by blood clots, including stroke, systemic embolism, heart attacks, blood clots on the stents and potentially even death. Antithrombotic therapy is required to decrease patients' risk of suffering blood clots and their consequences.

These patients need antiplatelets to reduce their risk of stent thrombosis and anticoagulation to reduce the risk of stroke. The combination of dual antiplatelet therapy and anticoagulation up to now has been a major challenge and has led to frequent bleeding complications. Addressing this challenge is at the heart of research in this area.

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 top 20 pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with approximately 50,000 employees. Since its founding in 1885, the company has remained family-owned and today creates value through innovation for three business areas including human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

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

In 2016, Boehringer Ingelheim achieved net sales of about $17.6 billion (15.9 billion euros). R&D expenditure corresponds to 19.6 percent of its net sales.

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

Boehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the trademarks Pradaxa® and RE-DUAL PCI™ under license.

SOURCE Boehringer Ingelheim

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