Leaderboard POC

ARISTOTLE: A randomized, double-blind controlled trial vs. warfarin in patients with AF

ELIQUIS demonstrated SUPERIORITY to warfarin for reduction in combined stroke or systemic embolism (SE) (primary efficacy endpoint)¹*

21% RRR: 1.27%/year vs. 1.60%/year for warfarin (HR 0.79, 95% CI: 0.66-0.95, p=0.0114)
- For systemic embolism; HR 0.87, 95% CI: 0.44-1.75

ARISTOTLE: Combined stroke and SE (primary efficacy endpoint) results in AF renal subgroups^†

ARISTOTLE: Combined stroke and SE (primary efficacy endpoint) results in age subgroups

ELIQUIS is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF); for the treatment of venous thromboembolic events (deep vein thrombosis [DVT], pulmonary embolism [PE]) and for the prevention of recurrent DVT and PE.¹

Patients with prosthetic heart valves, or those with hemodynamically significant rheumatic heart disease, especially mitral stenosis, were excluded from the ARISTOTLE trial and thus were not evaluated. The trial results do not apply to these patients, with or without atrial fibrillation.¹

Determine estimated creatinine clearance (eCrCl) in all patients before instituting ELIQUIS. ELIQUIS is not recommended in patients with creatinine clearance <15 mL/min, or in those undergoing dialysis. In AF patients, no dose adjustment is necessary in the elderly (>65 years), in patients with mild or moderate renal impairment, or in those with eCrCl 25-30 mL/min, unless the criteria for dose reduction are met. Patients with ≥2 of the “ABC” criteria should receive 2.5 mg BID (age ≥80 years, body weight ≤60 kg, creatinine level ≥133 μmol/L).¹

RRR = relative risk reduction; CI = confidence interval; HR = hazard ratio
† Patients with eCrCl <25 mL/min at baseline were excluded from the trial.¹

ARISTOTLE: A randomized, double-blind controlled trial in patients with AF

ELIQUIS demonstrated SUPERIORITY to warfarin for the primary safety endpoint of major bleeding^1†

31% RRR: 2.13%/year vs. 3.09%/year for warfarin (HR 0.69, 95% CI: 0.60-0.80, p<0.0001)

Major bleeding results (primary safety endpoint)
in AF renal subgroups^‡

Major bleeding results (primary safety endpoint)
in age subgroups

As with all anticoagulants, ELIQUIS should be used with caution in circumstances associated with an increased risk of bleeding. Bleeding can occur at any site during therapy with ELIQUIS. The possibility of a hemorrhage should be considered in evaluating the condition of any anticoagulated patient. An unexplained fall in hemoglobin, hematocrit or blood pressure should lead to a search for a bleeding site. Patients should be advised of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Patients at high risk of bleeding should not be prescribed ELIQUIS. Should severe bleeding occur, treatment with ELIQUIS must be discontinued and the source of bleeding investigated promptly. Close clinical surveillance (i.e., looking for signs of bleeding or anemia) is recommended throughout the treatment period. This may include looking for obvious signs of bleeding, e.g., hematomas, epistaxis or hypotension, testing for occult blood in the stool, checking serum hemoglobin for significant decrease, etc., especially if other factors/conditions that generally increase the risk of hemorrhage are also present.¹

Bleeding of any type was observed at a rate of 18% per year in AF patients. Common adverse reactions with ELIQUIS were epistaxis (6.2%), contusion (5.0%), hematuria (3.7%), hematoma (2.6%), hemorrhage (including eye [2.3%], gastrointestinal [2.1%], rectal [1.6%] and other [1.7%]) and gingival bleeding (1.2%).¹

† Major bleeding was defined as clinically overt bleeding accompanied by a decrease in the hemoglobin level of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site, or resulting in death.² Dataset includes events occurring on-treatment plus the following two days. Concomitant aspirin use with either ELIQUIS or warfarin increased the risk of major bleeding 1.5 to 2 times when compared with those patients not treated with concomitant aspirin. ELIQUIS should be used with caution in patients treated concomitantly with antiplatelet agents.¹
‡ Patients with eCrCl <25 mL/min at baseline were excluded from the trial.¹

AVERROES: A randomized, double-blind controlled trial vs. ASA in patients with AF

ELIQUIS demonstrated SUPERIORITY to ASA for reduction in combined stroke or systemic embolism (SE) (primary efficacy endpoint)¹*

55% RRR: 1.62%/year vs. 3.63%/year for ASA (HR 0.45, 95% CI: 0.32-0.62, p<0.0001)

AVERROES: Combined stroke and SE (primary
efficacy endpoint) results in AF renal subgroups^†

AVERROES: Combined stroke and SE (primary
efficacy endpoint) results in age subgroups

† Patients with eCrCl <25 mL/min at baseline were excluded from the trial.¹

AVERROES: A randomized, double-blind controlled trial vs. ASA in patients with AF

No statistically significant difference demonstrated in the incidence of major bleeding vs. ASA (primary safety endpoint)^1†

HR 1.54: 1.41%/year vs. 0.92%/year for ASA (95% CI: 0.96-2.45, p=0.0716)
Other bleeding results included:
- Major + CRNM bleeding:^‡ 4.46%/year vs. 3.24%/year for ASA (HR 1.38, 95% CI: 1.07-1.78, p=0.0144)
- All bleeding: 10.85%/year vs. 8.32%/year for ASA (HR 1.30, 95% CI: 1.10-1.53, p=0.0017)

Major bleeding results (primary safety endpoint) in AF renal subgroups^§

Major bleeding results (primary safety endpoint) in age subgroups

† Dataset includes events occurring on-treatment, plus the following two days for patients that did not enter the open-label extension. Major bleeding defined as clinically overt bleeding accompanied by ≥1 of the following: a decrease in the hemoglobin level of ≥2 g/dL over a 24-hour period, transfusion of ≥2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding.^1,2

‡ Clinically relevant non-major (CRNM) = clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to hospital admission, physician-guided medical or surgical treatment, or a change in antithrombotic therapy. Dataset includes events occurring on-treatment, plus the following two days for patients that did not enter the open-label extension.¹

§ Patients with eCrCl <25 mL/min at baseline were excluded from the trial.¹

Safety information

Clinical use:

Safety and efficacy not established in pediatric patients (<18 years); therefore, Health Canada has not authorized an indication for pediatric use.

Contraindications:

Clinically significant active bleeding, including gastrointestinal bleeding
Lesions or conditions at increased risk of clinically significant bleeding
Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
Concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-glycoprotein
Concomitant treatment with any other anticoagulant including unfractionated heparin, except at doses used to maintain a patent central venous or arterial catheter, low molecular weight heparins, such as enoxaparin and dalteparin, heparin derivatives, such as fondaparinux, and oral anticoagulants, such as warfarin, dabigatran, rivaroxaban, except under circumstances of switching therapy to or from apixaban

Most serious warnings and precautions:

Bleeding: if severe, discontinue
Peri-operative spinal/epidural anesthesia, lumbar puncture: increased risk of hematoma
INR monitoring: not a valid measure to assess anticoagulant activity of ELIQUIS
Premature discontinuation: increases risk of thrombotic events

Other relevant warnings and precautions:

Caution when used with drugs that affect hemostasis
Not recommended in patients with prosthetic heart valves or with hemodynamically significant rheumatic heart disease, especially mitral stenosis
Avoid use with strong inducers of both CYP3A4 and P-gp
Caution in patients with mild or moderate hepatic impairment (not recommended if severe) or elevated liver enzymes
Caution in patients ≥75 years in the treatment of DVT and PE and prevention of recurrent DVT and PE
Pre-operative/post-operative considerations
Not recommended as an alternative to unfractionated heparin for the treatment of VTE in patients with pulmonary embolism who are hemodynamically unstable, or who may receive thrombolysis or pulmonary embolectomy
Not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome (APS)
Renal impairment: not recommended if creatinine clearance <15 mL/min or dialysis; dosing adjustments may be required; renal function should be monitored
Not recommended in pregnant or nursing women
Hip fracture surgery patients

For more information:

Please consult the Product Monograph at https://www.bms.com/assets/
bms/ca/documents/productmonograph/ELIQUIS_EN_PM.pdf or https://www.pfizer.ca/pm/en/eliquis.pdf for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece.
The Product Monograph is also available by calling 1-866-463-6267.