Effective Date

Date of Origin 

10-01-2024            

Corlanor®

(ivabradine)

Tablet

Oral Solution

Reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction less than or equal to 35%, who are in sinus rhythm with resting heart rate greater than or equal to 70 beats per minute and either are on maximally tolerated doses of beta blockers or have a contraindication to beta-blocker use.

Treatment of stable symptomatic heart failure due to dilated cardiomyopathy (DCM) in pediatric patients aged 6 months and older, who are in sinus rhythm with an elevated heart rate.  

* generic available

1

Heart Failure

Heart failure (HF) is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. The American Heart Association/American College of Cardiology (AHA/ACC) stages of heart failure emphasize the development and progression of disease, and advanced stages and progression are associated with reduced survival. The New York Heart Association (NYHA) classification is used to characterize symptoms and functional capacity of patients with symptomatic (NYHA Class II-IV) HF or advanced HF. In HF, NYHA functional class I includes patients with no limitations in physical activity resulting from their HF. NYHA class II includes patients who are comfortable at rest but have slight symptoms resulting from HF (dyspnea, fatigue, lightheadedness) with ordinary activity. NYHA class III includes patients who are comfortable at rest but have symptoms of HF with less than ordinary activity. NYHA class IV includes patients who are unable to carry out any physical activity without symptoms and have symptoms at rest. It is a subjective assessment by a clinician and can change over time. Although reproducibility and validity can be limited, the NYHA functional classification is an independent predictor of mortality, and it is widely used in clinical practice to determine the eligibility of patients for treatment strategies. Because of the complexity of HF management and coordination of other health and social services required, HF care is ideally provided by multidisciplinary teams that include cardiologists, nurses, and pharmacists who specialize in HF as well as dieticians, mental health clinicians, social workers, primary care clinicians, and additional specialists.(3)

Left ventricular ejection fraction (LVEF) is considered important in the classification of patients with HF because of differing prognosis and response to treatments and because most clinical trials select patients based on ejection fraction (EF). The classification of HF by LVEF is as follows:(3)

The ACCF/AHA/HFSA (American College of Cardiology/Heart Failure Society of America) 2022 Guideline for the Management of Heart Failure states that ivabradine can be beneficial to reduce HF hospitalizations and cardiovascular death for patients with symptomatic (NYHA class II-III) stable chronic heart failure with reduced ejection fraction (HFrEF) (LVEF less than or equal to 35%) who are receiving guideline directed medical therapy (GDMT), including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.(3)

Treatment recommendations for HFrEF (LVEF less than or equal to 40%) for stages C (Structural heart disease with current or previous symptoms of HF) and D (Marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize GDMT) progress from step 1 to step 6 and are based on several individual patient factors. Step 1 medications may be started simultaneously at initial (low) doses recommended for HFrEF. Alternatively, these medications may be started sequentially, with sequence guided by clinical or other factors, without need to achieve target dosing before initiating next medication while increasing to target as tolerated. Step 1 medications with a class of recommendation (COR) of 1 (strong) are given to diuretics as needed; sodium-glucose cotransporter 2 inhibitor (SGLT2i); beta blocker; mineralocorticoid receptor antagonist [MRA]; angiotensin receptor-neprilysin inhibitor [ARNi] in NYHA II-III, angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB] in NYHA II-IV).(3)

DCM

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different etiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases.  The heterogeneous etiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodeling. Immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter–defibrillators may be required to prevent life-threatening arrhythmias.(4)

Efficacy

Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the I current, resulting in heart rate reduction with no effect on ventricular repolarization and no effects on myocardial contractility.(1)

It gained its indication for heart failure in adult patients via the systolic heart failure treatment with the If inhibitor ivabradine trial (SHIFT). This was a randomized, double-blind trial comparing Corlanor and placebo in 6558 patients with stable NYHA class II to IV heart failure, left ventricular ejection fraction less than or equal to 35%, and resting heart rate greater than or equal to 70 bpm. Patients had to have been clinically stable for at least 4 weeks on an optimized and stable clinical regimen, which included maximally tolerated doses of beta blockers and, in most cases, ACE inhibitors or ARBs, spironolactone, and diuretics, with fluid retention and symptoms of congestion minimized. Patients had to have been hospitalized for heart failure within 12 months prior to study entry. SHIFT demonstrated that Corlanor reduced the risk of the combined endpoint of hospitalization for worsening heart failure or cardiovascular death based on a time-to-event analysis.(1)

Because Corlanor was effective in improving outcomes in patients with dilated cardiomyopathy (DCM) in SHIFT, the effect on heart rate was considered a reasonable basis to infer clinical benefits in pediatric patients with DCM. Thus, Corlanor was evaluated for its effect on heart rate in a multi-center, randomized, double-blind, placebo-controlled trial in children with symptomatic DCM. The study collected data from 116 patients 6 months to less than 18 years old with DCM in sinus rhythm, NYHA/Ross class II to IV heart failure, and left ventricular ejection fraction less than or equal to 45%. A statistically significant reduction in heart rate was observed with Corlanor compared to placebo at the end of the titration period (-23 plus or minus 11 bpm vs. -2 plus or minus 12 bpm respectively).(1)

Safety

Ivabradine is contraindicated in patients with:(1)

• Acute decompensated heart failure
• Clinically significant hypotension
• Sick sinus syndrome, sinoatrial block, or 3rd degree AV block, unless a functioning demand pacemaker is present
• Clinically significant bradycardia
• Severe hepatic impairment
• Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
• Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors

1

Corlanor prescribing information. Amgen Inc. August 2021.

2

Reference no longer used 

3

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18). doi:10.1161/cir.0000000000001063

4

Schultheiss HP, Fairweather D, Caforio ALP, et al. Dilated cardiomyopathy. Nature Reviews Disease Primers. 2019;5(1). doi:10.1038/s41572-019-0084-1

Corlanor

ivabradine hcl oral soln

5 MG/5ML

M ; N ; O ; Y

N

Corlanor

ivabradine hcl tab

5 MG ; 7.5 MG

M ; N ; O ; Y

O ; Y

Corlanor

ivabradine hcl oral soln

5 MG/5ML

600

mLs

30

DAYS

Corlanor

ivabradine hcl tab

5 MG ; 7.5 MG

60

Tablets

30

DAYS

Corlanor

ivabradine hcl oral soln

5 MG/5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Corlanor

ivabradine hcl tab

5 MG ; 7.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Corlanor

ivabradine hcl oral soln

5 MG/5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Corlanor

ivabradine hcl tab

5 MG ; 7.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. The patient has a diagnosis of stable symptomatic heart failure (NYHA Class II-IV) due to dilated cardiomyopathy (DCM) AND BOTH of the following:
      1. The patient is in sinus rhythm AND
      2. The patient has an elevated heart rate OR
   3. The patient has a diagnosis of stable symptomatic chronic heart failure (NYHA Class II-IV) AND ALL of the following:
      1. The patient has a left ventricular ejection fraction (LVEF) less than or equal to 35% AND
      2. The patient is in sinus rhythm AND
      3. The patient has a resting heart rate of greater than or equal to 70 beats per minute AND
      4. ONE of the following: 
         1. BOTH of the following:
            1. The patient is currently treated with a maximally tolerated beta blocker AND
            2. The patient will continue beta blocker therapy OR
         2. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to beta blocker therapy OR
   4. The patient has another FDA labeled indication for the requested agent and route of administration OR
   5. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS or DrugDex 1 or 2a level of evidence 

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.


Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QL with PA

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of approval: up to 12 months