2016

November 18 – 20

Georgia Chapter Annual Meeting 2016

The Ritz-Carlton at Reynolds Plantation Greensboro , GA

November 19

Mid Atlantic Capital Cardiology Symposium 2016

Heart House Washington , DC

December 2 – 3

How to Become a Cardiovascular Investigator

Heart House Washington , DC

December 9 – 11

New York Cardiovascular Symposium

New York Hilton New York

December 14 – 16

Teaching Skills Workshop for Emerging Faculty

Heart House Washington , DC

2017

January 14 – 18

Cardiovascular Conference at Snowmass Gold Package

The Westin Snowmass Resort Snowmass , CO

January 26 – 28

Cardiovascular Summit & Leadership Forum : Finance , Operations , Quality and Data

Hilton Bonnet Creek Orlando , FL

February 17 – 18

Advancing Cardiovascular Care of the Oncology Patient

Park Hyatt Washington Washington , DC

Pradaxa ® ( dabigatran etexilate mesylate ) capsules , for oral use

BRIEF SUMMARY OF PRESCRIBING INFORMATION Please see package insert for full Prescribing Information .

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 [ see Warnings and Precautions ].

( 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 antiinflammatory 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 [ see Warnings and Precautions ].

Monitor patients frequently for signs and symptoms of neurological impairment . If neurological compromise is noted , urgent treatment is necessary [ see Warnings and Precautions ]. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [ see Warnings and Precautions ].

INDICATIONS AND USAGE : Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation : PRADAXA is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation . Treatment of Deep Venous Thrombosis and Pulmonary Embolism : PRADAXA is indicated for the treatment of deep venous thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for 5-10 days . Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism : PRADAXA is indicated to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in patients who have been previously treated .

CONTRAINDICATIONS : PRADAXA is contraindicated in patients with : Active pathological bleeding [ see Warnings and Precautions and Adverse Reactions ]; History of a serious hypersensitivity reaction to PRADAXA ( e . g ., anaphylactic reaction or anaphylactic shock ) [ see Adverse Reactions ]; Mechanical prosthetic heart valve [ see Warnings and Precautions ].

WARNINGS AND 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 the concomitant use of other drugs 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 the clinical experience supporting the use of hemodialysis as a treatment for bleeding is limited [ see Overdosage ]. Prothrombin complex concentrates , or recombinant Factor VIIa may be considered but their use has not been evaluated in clinical trials . Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of dabigatran . Consider administration of platelet concentrates in cases where thrombocytopenia is present or long-acting antiplatelet drugs have been used . Spinal / Epidural Anesthesia or Puncture : When neuraxial anesthesia ( spinal / epidural anesthesia ) or spinal puncture is employed , patients treated with anticoagulant agents are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis [ see Boxed Warning ]. To reduce the potential risk of bleeding associated with the concurrent use of dabigatran and epidural or spinal anesthesia / analgesia or spinal puncture , consider the pharmacokinetic profile of dabigatran . Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of dabigatran is low ; however , the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known . Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia / analgesia or lumbar puncture , monitor frequently to detect any signs or symptoms of neurological impairment , such as midline back pain , sensory and motor deficits ( numbness , tingling , or weakness in lower limbs ), bowel and / or bladder dysfunction . Instruct

February 20 – 24

Big Sky Cardiovascular Update : Practical Applications in Clinical Cardiology

The Huntley Lodge Big Sky , MT

patients to immediately report if they experience any of the above signs or symptoms . If signs or symptoms of spinal hematoma are suspected , initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae . Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves : The safety and efficacy of PRADAXA in patients with bileaflet mechanical prosthetic heart valves was evaluated in the RE-ALIGN trial , in which patients with bileaflet mechanical prosthetic heart valves ( recently implanted or implanted more than three months prior to enrollment ) were randomized to dose adjusted warfarin or 150 , 220 , or 300 mg of PRADAXA twice a day . RE-ALIGN was terminated early due to the occurrence of significantly more thromboembolic events ( valve thrombosis , stroke , transient ischemic attack , and myocardial infarction ) and an excess of major bleeding ( predominantly post-operative pericardial effusions requiring intervention for hemodynamic compromise ) in the PRADAXA treatment arm as compared to the warfarin treatment arm . These bleeding and thromboembolic events were seen both in patients who were initiated on PRADAXA post-operatively within three days of mechanical bileaflet valve implantation , as well as in patients whose valves had been implanted more than three months prior to enrollment . Therefore , the use of PRADAXA is contraindicated in patients with mechanical prosthetic valves [ see Contraindications ]. The use of PRADAXA for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease , including the presence of a bioprosthetic heart valve , has not been studied and is not recommended . Effect of P-gp Inducers and Inhibitors on Dabigatran Exposure : The 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 the major independent factors that result in increased exposure to dabigatran . Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone . Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation : Reduce the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA in patients with moderate renal impairment ( CrCl 30-50 mL / min ). Avoid use of PRADAXA and P-gp inhibitors in patients with severe renal impairment ( CrCl 15-30 mL / min ) [ see Drug Interactions and Use in Specific Populations ]. Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism : Avoid use of PRADAXA and concomitant P-gp inhibitors in patients with CrCl < 50 mL / min [ see Drug Interactions ].

ADVERSE REACTIONS : The following serious adverse reactions are described elsewhere in the labeling : Increased Risk of Thrombotic Events after Premature Discontinuation [ see Warnings and Precautions ]; Risk of Bleeding [ see Warnings and Precautions ]; Spinal / Epidural Anesthesia or Puncture [ see Warnings and Precautions ]; Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves [ see Warnings and Precautions ]. The most serious adverse reactions reported with PRADAXA were related to bleeding [ see Warnings and Precautions ]. Clinical Trials Experience : Because clinical trials are conducted under widely varying conditions , adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice . Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation : The RE-LY ( Randomized Evaluation of Long-term Anticoagulant Therapy ) study provided safety information on the use of two doses of PRADAXA and warfarin . The numbers of patients and their exposures are described in Table 1 . Limited information is presented on the 110 mg dosing arm because this dose is not approved .

Table 1 Summary of Treatment Exposure in RE-LY

PRADAXA 110 mg twice daily

PRADAXA 150 mg twice daily

Warfarin

Drug Discontinuation in RE-LY : The rates of adverse reactions leading to treatment discontinuation were 21 % for PRADAXA 150 mg and 16 % for warfarin . The most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding and gastrointestinal events ( i . e ., dyspepsia , nausea , upper abdominal pain , gastrointestinal hemorrhage , and diarrhea ). Bleeding [ see Warnings and Precautions ]: Table 2 shows the number of adjudicated major bleeding events during the treatment period in the RE-LY study , with the bleeding rate per 100 subject-years (%). Major bleeding is defined as bleeding accompanied by one or more of the following : a decrease in hemoglobin of ≥2 g / dL , a transfusion of ≥2 units of packed red blood cells , bleeding at a critical site or with a fatal outcome . Intracranial hemorrhage included intracerebral ( hemorrhagic stroke ), subarachnoid , and subdural bleeds .

Table 2 Adjudicated Major Bleeding Events in Treated

Patients a

Event

PRADAXA 150 mg N = 6059 n (%/ year b )

Warfarin N = 5998 n (%/ year b )

PRADAXA 150 mg vs . Warfarin HR ( 95 % CI )

April 8

West Virginia Chapter-ACC 12th Annual Meeting

The Charleston Marriott Town Center Charleston , WV

Table 2 ( Cont ' d ) Event

PRADAXA 150 mg N = 6059 n (%/ year b )

Warfarin N = 5998 n (%/ year b )

PRADAXA 150 mg vs . Warfarin HR ( 95 % CI )

and subdural bleeds .

e

On-treatment analysis based on the safety population , compared to ITT analysis presented in Section 14 Clinical Studies .

f

Fatal bleed : Adjudicated major bleed as defined above with investigator reported fatal outcome and adjudicated death with primary cause from bleeding .

g

Non-intracranial fatal bleed : Adjudicated major bleed as defined above and adjudicated death with primary cause from bleeding but without symptomatic intracranial bleed based on investigator ’ s clinical assessment .

There was a higher rate of any gastrointestinal bleeds in patients receiving PRADAXA 150 mg than in patients receiving warfarin ( 6.6 % vs . 4.2 %, respectively ). The risk of major bleeds was similar with PRADAXA 150 mg and warfarin across major subgroups defined by baseline characteristics ( see Figure 1 , below ), with the exception of age , where there was a trend towards a higher incidence of major bleeding on PRADAXA ( hazard ratio 1.2 , 95 % CI : 1.0 to 1.5 ) for patients ≥75 years of age . Gastrointestinal Adverse Reactions : Patients on PRADAXA 150 mg had an increased incidence of gastrointestinal adverse reactions ( 35 % vs . 24 % on warfarin ). These were commonly dyspepsia ( including abdominal pain upper , abdominal pain , abdominal discomfort , and epigastric discomfort ) and gastritislike symptoms ( including GERD , esophagitis , erosive gastritis , gastric hemorrhage , hemorrhagic gastritis , hemorrhagic erosive gastritis , and gastrointestinal ulcer ). Hypersensitivity Reactions : In the RE-LY study , drug hypersensitivity ( including urticaria , rash , and pruritus ), allergic edema , anaphylactic reaction , and anaphylactic shock were reported in < 0.1 % of patients receiving PRADAXA . Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism : PRADAXA was studied in 4387 patients in 4 pivotal , parallel , randomized , double-blind trials . Three of these trials were active-controlled ( warfarin ) ( RE-COVER , RE-COVER II , and RE-MEDY ), and one study ( RE-SONATE ) was placebo-controlled . The demographic characteristics were similar among the 4 pivotal studies and between the treatment groups within these studies . Approximately 60 % of the treated patients were male , with a mean age of 55.1 years . The majority of the patients were white ( 87.7 %), 10.3 % were Asian , and 1.9 % were black with a mean CrCl of 105.6 mL / min . Bleeding events for the 4 pivotal studies were classified as major bleeding events if at least one of the following criteria applied : fatal bleeding , symptomatic bleeding in a critical area or organ ( intraocular , intracranial , intraspinal or intramuscular with compartment syndrome , retroperitoneal bleeding , intra-articular bleeding , or pericardial bleeding ), bleeding causing a fall in hemoglobin level of 2.0 g / dL ( 1.24 mmol / L or more , or leading to transfusion of 2 or more units of whole blood or red cells ). RE-COVER and RE-COVER II studies compared PRADAXA 150 mg twice daily and warfarin for the treatment of deep vein thrombosis and pulmonary embolism . Patients received 5-10 days of an approved parenteral anticoagulant therapy followed by 6 months , with mean exposure of 164 days , of oral only treatment ; warfarin was overlapped with parenteral therapy . Table 3 shows the number of patients experiencing bleeding events in the pooled analysis of RE-COVER and RE-COVER II studies during the full treatment including parenteral and oral only treatment periods after randomization .

Table 3 Bleeding Events in RE-COVER and RE-COVER II Treated Patients

Bleeding Events-Full Treatment Period Including Parenteral Treatment

PRADAXA 150 mg twice daily N (%)

Warfarin N (%)

Hazard Ratio ( 95 % CI ) c