Elizabeth J. Walls, MSN, ANP-BC · Perindopril/Amlodipine (Prestalia) ›Combination drug indicated...
Transcript of Elizabeth J. Walls, MSN, ANP-BC · Perindopril/Amlodipine (Prestalia) ›Combination drug indicated...
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