Elizabeth J. Walls, MSN, ANP-BC

None

Gain the knowledge to identify the

pharmacodynamics for new

medications in cardiology.

Refresh knowledge and redefine current

pharmacology practice.

Lipid Management

Anticoagulation/Antiplatelets

Heart Failure Management

“Other” New Cardiac Drugs

PCSK-9 Inhibitors- FDA Approved 2015

› Alirocumab (Praluent)

› Evolocumab (Repatha)

Second line treatment for hyperlipidemia

for those not adequately controlled on

statins and dietary modification.

How do PCSK-9 inhibitors work?

Alirocumab (Praluent)

› SQ Injection

› Initial dose 75mg once every 2 weeks; may

be titrated up to 150mg every 2 weeks based on LDL response.

› Available in prefilled syringe or pen injector,

75mg/1ml or 150mg/1ml. Cost per syringe is $672.00.

› No dose adjustment for renal or hepatic

impairment. No special geriatric considerations. Not studied in pregnancy.

Alirocumab (Praluent)

› Repeat LDL within 4-8 weeks to monitor for achievement of LDL goal

› Minimal side effects reported. Most common

were hypersensitivity reactions or injection

site reactions.

› Patient Education

How to give a SQ injection; rotate injection

sites.

Syringes must be kept refrigerated and then

left out at room temp 30-40 min prior to

injection.

Evolocumab (Repatha)

› SQ injection

› Dosage: 140mg every 2 weeks or 420mg

monthly

› Available in auto injector pen or prefilled

syringe 140mg/1ml or solution cartridge

420mg/3.5ml. Cost is $670.30 and $1452.30 respectively.

› No dose adjustment for renal or hepatic

impairment. No special geriatric considerations. Not studied in pregnancy.

Evolocumab (Repatha)

› Repeat LDL within 4-8 weeks to monitor for achievement of LDL goal

› Minimal side effects reported. Most common

were hypersensitivity reactions or injection

site reactions.

› Patient Education

How to give a SQ injection; rotate injection

sites.

Syringes must be kept refrigerated and then

left out at room temp 30 min prior to injection.

Research Trials

› SPIRE-1 & SPIRE-2

› ODYSSEY

› IMPROVE-IT

Hot of the presses!!- Presented at ACC.17

› FOURIER

PCSK9 Inhibitors are extremely effective

and safe.

PCSK-9 Inhibitor Special Considerations

› Cost is a concern; some financial assistance

and special programs through pharm

companies.

› Only available from specialty pharmacies.

› LOTS of paperwork for the provider!

› Is patient or caregiver capable of giving

injection and remembering to do so on set

schedule?

Niacin (Niaspan, Niacor, Slo-Niacin) › Indicated for treatment of dyslipidemias as a

mono- or adjunctive therapy; adjunctive therapy for severe hypertriglyceridemia putting patients at risk for pancreatitis.

› Available in immediate or sustained release tablets; recommended dosage 2-3 g daily in divided doses.

› Cost is brand dependent but overall relatively cheap and available in OTC formulations.

HPS2-THRIVE Trail

› No reduction in MACE

› Increase in serious adverse side effects

› Showed increased levels of HDL overall but no increased benefits to patient

Serious adverse effects included:

› Increased risk of DM

› Makes DM more difficult to control

› Increased GI, musculoskeletal and skin

complaints. The FLUSHING!!

Should we still be prescribing Niacin in

the management of hyperlipidemia?

Not routinely but it may benefit some.

Non-Vitamin K Oral Anticoagulants (NOACs) › Dabigatran (Pradaxa)

› Rivaroxaban (Xarelto)

› Apixaban (Eliquis)

› Latest and greatest

Edoxaban (Savaysa)

Reversal Agents for NOAC’s › Idarucizumab (Praxbind)

Edoxaban (Savaysa)

› Direct oral anticoagulant indicated for stroke

prevention in nonvalvular atrial fibrillation and

treatment of DVT/PE.

› Oral tablet. Dosages: Afib-60mg once daily;

DVT/PE-60mg once daily unless weight <60kg

then 30mg daily.

› Renal dose adjustment for CrCl 15-50 mL/min.

Use not recommended for CrCl <15 mL/min.

› Carries a US Box warning for reduced efficacy in

nonvalvular atrial fibrillation patients with CrCl

>95 mL/minute.

Edoxaban (Savaysa)

› Not recommended for use in moderate to

severe hepatic impairment.

› Monthly cost $628.80.

› Most common adverse side effect is bleeding.

Make sure your patients know what to look for and

what to report!

Epidural or spinal hematomas may occur in

patients treated with edoxaban who are receiving

neuraxial anesthesia or undergoing spinal

puncture. (US Box Warning)

Special Considerations for NOACs

› Less food and drug interactions than

warfarin.

› No special monitoring.

› Quick onset of action and shorter half-life

› Reversal agent only available for Pradaxa

› Higher cost

Idarucizumab (Praxbind) › Indicated for the urgent reversal of

dabigatran anticoagulation.

› REVERSE-AD Trial

› Recommended dose of idarucizumab is 5 g administered in 2 divided consecutive doses (2.5 g each) by IV infusion or rapid IV injection.

› No dose adjustment for renal impairment; not studied in hepatic impairment.

› Dabigatran therapy can be reinitiated 24 hours after administration.

Idarucizumab (Praxbind)

› Biggest concern with reversal…

Exposes patients to their underlying thrombotic

risk.

› Adverse side effects reported in REVERSE-AD

were hypokalemia, delirium, constipation,

pyrexia, pneumonia and headache.

› The average wholesale price for a 5 g dose

of Praxbind is $3500.

Ongoing trials for reversal agents

› Adaxanet alfa

ANEXXA-4; phase 4 clinical trials

IV bolus and infusion

› Ciraparantag

In phase 2 clinical trials

Single bolus IV injection

The triple therapy controversy

› Patient with CAD and Afib or CAD and VTE

› Triple therapy increases major bleeding

events.

› New studies suggest there is no statistically

significant difference of bleeding risk and risk of MACE between dual therapy with a

NOAC and P2Y12 and triple therapy.

› More to come!!

Cangrelor (Kengreal)

› IV Antiplatelet agent

› Adjunct to PCI to reduce the risk of

periprocedural myocardial infarction (MI),

repeat coronary revascularization, and stent

thrombosis in patients who have not been

treated with a P2Y12 platelet inhibitor and

are not being given a glycoprotein IIb/IIIa

inhibitor.

› Used (off-label) as a bridge to CV surgery.

Cangrelor (Kengreal)

› Dose: 30 mcg/kg bolus prior to PCI followed

immediately by an infusion of 4

mcg/kg/minute continued for at least 2 hours or for the duration of the PCI,

whichever is longer.

› After discontinuation, a loading dose of oral P2Y12 Inhibitor should be given immediately.

› This is all getting done in the cath lab!

› For fun…cost of standard dosage to treat one patient is $749.

Case Scenario

› Mr. T. is a 59-year old gentleman with

essentially no PMH who is s/p STEMI. Echo

demonstrates EF 30-35% and patient has shown some signs of volume overload. His

BNP is 3500. His BUN/Creat are 26/0.6. He is

already on aspirin, ticagrelor and atorvastatin for his CAD. What other

appropriate medical therapy should be

initiated for his HFrEF?

Pharm Review of the 2013 ACC/AHA

Guidelines

› ACE-Inhibitors (ARB’s for those ACE-I

intolerant)

› Beta Blockers

› Diuretics (if evidence of fluid retention)

› Aldosterone Receptor Antagonists

› Hydralazine and Isosorbide Dinitrate

› Digoxin (class IIb rec)

2016 ACC/AHA/HFSA Focused update on Pharmacological Therapy › angiotensin receptor–neprilysin inhibitors

(ARNI) given a class I recommendation as an alternative to ACE-I/ARB’s.

› Class IIa recommendation for use of ivabradine to reduce HF hospitalization in patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤35%) receiving guideline-directed evaluation and management.

Sacubitril/Valsartan (Entresto) › Combination Angiotensin II Receptor Blocker

& Neprilysin Inhibitor

› Indicated for the treatment of HFrEF

› Reduce risk of CV death and hospitalization related to HF.

› Starting dose 49/51mg oral twice daily; double dose every 2-4 weeks to achieve target dose of 97/103mg twice daily.

› Available dosages: 24/26mg; 49/51mg; 97/103mg.

Sacubitril/Valsartan (Entresto)

› Lower initial dose of 24/26mg should be used

in patients with renal impairment or those

who are ACE/ARB naïve.

› Should not be used in severe hepatic

impairment.

› Most reported adverse side effects included

angioedema, hypotension, hyperkalemia, impaired renal function and fetal toxicity.

Some discussion about risk for dementia.

Sacubitril/Valsartan (Entresto)

› Special Considerations

Replaces ACE/ARB- should wait 36 hours after

discontinuation before starting.

Long-term safety remains unknown

Monitor renal function, electrolytes & BP

Ensure patient is on adequate birth control if of

child bearing age.

Ivabradine (Corlanor)

› Indicated in HFrEF to reduce the risk of

hospitalization for worsening heart failure.

› For patients in sinus rhythm with resting heart rate ≥70 bpm and either are on maximally

tolerated doses of beta blockers or have a

contraindication to beta-blocker use.

› Disrupts ion current flow, prolonging diastolic

depolarization and slowing firing of SA node.

Ivabradine (Corlanor) › Used off label for inappropriate sinus

tachycardia and stable angina

› Initial dose 2.5 to 5mg twice daily; increase dose by 2.5mg to achieve HR of 50-60 bpm (max dose 7.5mg).

› Should not use in patients with acute decompensated HF or those with atrial fibrillation.

› Most common adverse reactions: bradycardia, hypertension, Afib, heart block.

Aspirin/Omeprazole (Yosprala)

› Indicated for secondary prevention of

cardiovascular and cerebrovascular events

in patients at risk for developing gastric ulcers.

› Dosage: aspirin 81mg/omeprazole 40mg or

aspiring 325mg/omeprazole 40mg. Cost is

about $180 for both dosages.

› Avoid in hepatic impairment; avoid in renal

impairment with GFR <10ml/min.

Aspirin/Omeprazole (Yosprala)

› Most common side effects: indigestion,

heartburn, nausea, stomach pain, chest

pain, diarrhea and growths in the stomach.

› Monitoring: long term use can effect

magnesium and vitamin B12 levels. It has

also been associated with bone fractures

and Clostridium Difficile

Aspirin/Omeprazole (Yosprala)

› Special considerations:

Use with Plavix remains controversial.

Studies showed increased compliance with

taking medications.

Although studies did show decreased risk of

developing gastric ulcers it did not effect rates

of GI bleeding.

Is it cost effective for 2 relatively cheap,

generic, OTC medications??

Perindopril/Amlodipine (Prestalia)

› Combination drug indicated for the

management of hypertension.

› Oral tablet, once daily dosing

› Available doses: 3.5/2.5mg; 7/5mg; 14/10mg

› Similar profile, adverse effects and

monitoring to individual drugs.

Nebivolol/Valsartan (Byvalson)

› Indicated for the management of

hypertension where BP not managed with

Valsartan alone or patient already on both.

› Oral tablet, once daily dosing

› Available dosage 5/80mg

› Similar profile, adverse effects and

monitoring to individual drugs.

PCSK9 Inhibitors are the way of the future

in lipid management.

The age of routine use of Niacin is over.

NOACs are less cumbersome than

warfarin and are comparable or better

in regards to bleeding risk. Reversal

agents are in the works!

Dual therapy with anticoagulant and

antiplatelet is probably just as effective

as triple therapy.

The newest additions to the HF

management family are ARNI’s and

ivabradine.

New combination formulas available for

management of hypertension and

secondary CV disease preve3nti