Boehringer Ingelheim Presents First Head-to-Head Matched Population Comparison of All-Cause Costs and Healthcare Resource Utilization among Novel Oral Anticoagulants

Ridgefield, CT, May 30, 2017 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced results from the first real-world, matched head-to-head study comparing all-cause healthcare costs and healthcare resource utilization (HCRU) among novel oral anticoagulants (NOACs). This real-world healthcare economic comparison is not intended to suggest a clinical comparison between NOACs. The claims analysis found that Pradaxa® (dabigatran etexilate mesylate) was associated with lower all-cause costs and HCRU compared to rivaroxaban. Compared to apixaban, PRADAXA was associated with similar all-cause costs and hospitalizations, but higher all-cause outpatient and pharmacy HCRU. The results were presented at the International Society for Pharmacoeconomics and Outcomes Research 22^nd Annual International Meeting in Boston, MA.

The approved labeling for PRADAXA does not include data comparing the product to other NOAC therapies, and there are no clinical trials providing a head-to-head comparison of NOAC therapies. PRADAXA is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF).

“While many studies have examined real-world outcomes with NOACs relative to warfarin, this is one of the first studies to compare NOACs against each other in terms of their impact on costs and HCRU,” said Stacey Long, senior vice president and general manager, Truven Health Life Sciences, IBM Watson Health. “This study provides valuable insights that can help physicians better understand the costs to patients and our healthcare system associated with NOAC treatment decisions.”

The study analyzed data from 70,898 newly-diagnosed NVAF patients who were newly treated with PRADAXA, rivaroxaban or apixaban. The analysis used claims data collected between April 1, 2010 and December 31, 2015 from two Truven Health Analytics MarketScan Databases, which included Medicare beneficiaries and enrollees in commercial insurance plans. Truven Health Analytics is now part of the IBM Watson Health business. The study propensity-score matched PRADAXA patients 1:1 with 26,592 rivaroxaban and 8,857 apixaban patients.

The primary outcome for the study was all-cause healthcare costs per-patient per-month (PPPM), while the secondary outcome was all-cause HCRU PPPM. Compared with rivaroxaban, PRADAXA was associated with significantly lower average PPPM total costs ($4,145 vs. $4,602; p<0.001) and inpatient costs ($1,471 vs. $1,856; p<0.01) in descriptive analyses; multivariate analyses found PRADAXA was associated with significantly lower total costs ($4,093 vs. $4,636; p<0.001), inpatient costs ($1,476 vs. $1,862; p<0.001), outpatient costs ($2,016 vs. $2,121; p<0.01) and pharmacy costs ($634 vs. $645; p<0.05).

For the primary outcome of the study, when compared with apixaban, PRADAXA was associated with similar average PPPM total costs ($3,862 vs. $3,998 and $3,866 vs. $3,951; in descriptive and multivariate analyses, respectively), inpatient costs ($1,222 vs. $1,390; $1,258 vs. $1,336), outpatient costs ($1,959 vs. $1,912; $1,943 vs. $1,924) and pharmacy costs ($682 vs. $697; $681 vs. $692).

For the secondary outcome, the authors found that PRADAXA was associated with significantly lower all-cause HCRU compared to rivaroxaban, including fewer inpatient admissions (0.058 vs. 0.066; p=0.003), outpatient visits (4.845 vs. 4.962; p=0.019) and outpatient pharmacy claims (4.805 vs. 4.932; p=0.002). Compared to apixaban, PRADAXA was associated with significantly higher outpatient visits (4.704 vs. 4.310; p<0.001) and outpatient pharmacy claims (4.855 vs. 4.614; p=0.005), but with similar inpatient admissions (0.053 vs. 0.048; p=0.150). For additional details on the study, please refer to the abstract. 

“Hospitalizations and office visits related to NVAF cost the U.S. healthcare system over $6 billion each year,” said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “At Boehringer Ingelheim, we are committed to studying our therapies in real-world settings, and believe this analysis provides important new information on the economic impact of treatment with PRADAXA, which has the longest real-world experience of any available NOAC.”

Study Limitations

Study limitations are those inherent to any retrospective claims-based studies. Data may be subject to coding and data entry error, as NVAF was defined based on diagnosis and procedure codes. Medication exposure was based on filled prescriptions with the assumption that patients had taken the medication as prescribed. Findings may not be generalizable to NVAF patients with other insurance (other than commercial/private Medicare supplemental) or without health insurance.

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.

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.

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