Document

Report
Mending a Broken Heart:
Medications When Your Patient is on
Standard Therapy and Still Short of Breath
Dawn M. Waddell, PharmD, BCPS
Cardiothoracic Transplant & MCS Pharmacist, BMH - Memphis
Associate Faculty, UTHSC College of Pharmacy
No relevant financial relationships to disclose
Objectives
• Review medication interventions in patients at
risk for developing heart failure (HF)
• Discuss medications that may cause or worsen
HF
• Review current guidelines to optimize
medication therapy
• Review medication options in Stage D patients
• Evaluate new therapies under investigation for
specific populations of HF patients
Prevention
• Treat hypertension
– Long-term treatment of systolic and diastolic HTN decreases HF
risk by ~50%
• CAD/Atherosclerosis
– Add statin
• Identify and treat pre-diabetes
– Metformin can be added to diet and exercise if Hb A1C 5.7-6.4%
• Control diabetes
– Every 1% increase in HbA1c = 8% increase in HF risk (median
follow up 2.2 years)
– RR of developing HF in DM patients = 1.85 (median follow up 19
years)
Diabetes and HF
• FDA: metformin can be used in HF without
severe LV dysfunction if stable hemodynamics
and adequate renal function
• Metformin decreases all-cause mortality in HF
patients
• Metformin safe in patients with advanced HF
• Lower 1-year mortality and re-hospitalization
rates in HF patients compared to
insulin/sulfonylureas
Diabetes and HF
• Pioglitazone (Actos®)
– Increase in peripheral edema, incidence of new HF, HF
progression and hospitalizations
– Increased mortality not shown at this time
– Recommended with caution in NYHA I-II but avoid in
symptomatic HF patients
• DPP-4 inhibitors
– Saxagliptin (Onglyza®) associated with 0.75% and 0.3%
increased risk of HF hospitalizations in patients with and
without previous HF
– Sitagliptin (Januvia®) trial scheduled to report results June 2015
• Sodium-glucose cotransporter-2 inhibitors
– Dapagliflozin (Farxiga®): long-term studies on CV outcomes
underway
Medications to (Ideally) Avoid in HF
• Non-dihydropyridine calcium channel blockers
– Verapamil/Diltiazem decrease cardiac output
– Amlodipine: neutral; preferred > Felodipine/Nifedipine
• Antiarrhythmics
– Avoid class I, class III antiarrhythmics
– Amiodarone/Dofetilide recommended in HF
• NSAIDs
– Including COX-2 inhibitors
• Steroids
– Minimize doses
• Chemotherapy
– Anthracyclines, high-dose cyclophosphamide, trastuzumab,
bevacizumab
• TNF-alpha inhibitors
– Infliximab (Remicade®), Adalimumab (Humira®)
Optimize Standard Therapy
•
•
•
•
•
•
•
Titrate to goal HF doses
Beta blockers
ACE-Is
ARBs
Aldosterone antagonists
Hydralazine/Isosorbide
Digoxin
Beta Blockers
HF approved BB
Initial dose
Goal dose
Carvedilol
(Coreg®)
3.125 mg BID
25 mg BID (<85 kg) Yes
50 mg BID (>85 kg)
Metoprolol
succinate
(Toprol XL®)
12.5 mg DAILY 200 mg DAILY
Yes
No
Bisoprolol
(Zebeta®)
2.5 mg DAILY
Yes
Yes, with HCTZ
10 mg DAILY
• Avoid abrupt withdrawal
TennCare
Exempt List
$4 Generic
Lists
Yes
Beta Blockers
Carvedilol
• Improved BP control
• Usually improved
tolerability compared to
metoprolol in regards to
fatigue/depressive adverse
effects
• Usually tolerated in COPD
(>asthma) unless severe
Metoprolol succinate
• May be used in patients
who tend to be hypotensive
• May have advantage in
patients with ventricular
arrhythmias
• May be used in patients
with COPD/asthma
ACE-Inhibitors
ACE-Is
Initial Dose
Goal Dose
TennCare
Exempt List
$4 Generic
Lists
Captopril
(Capoten®)
6.25 mg TID
50 mg TID
No
No
Enalapril
(Vasotec®)
2.5 mg BID
10-20 mg BID
No
Yes, with
HCTZ
Benazepril
(Lotensin®)
5-10 mg DAILY
40-80 mg DAILY No
or divided BID
Yes
Lisinopril
(Zestril®)
2.5-5 mg DAILY
20-40 mg DAILY
No
Yes
+/- HCTZ
Perindopril
(Aceon®)
2 mg DAILY
8-16 mg DAILY
Yes
No
Quinapril
(Accupril®)
5 mg BID
20 mg BID
No
No
Ramipril
(Altace®)
1.25-2.5 mg DAILY 10 mg DAILY
No
No
ACE-Inhibitors
• Caution in patients with SBP < 80 mmHg, SCr >
3.0 mg/dL, K > 5.0 meq/L, bilateral renal
artery stenosis
• Check SCr and K every 1-2 weeks with
initiation of therapy and dose increases
• ~20% of patients experience cough
• Angioedema occurs in <1% but higher rate in
African Americans
ARBs
ARBs
Initial Dose
Goal Dose
TennCare
Exempt List
$4 Generic
Lists
Candesartan
(Atacand®)
4-8 mg DAILY
32 mg DAILY
Yes
No
Losartan
(Cozaar®)
25-50 mg DAILY 50-150 mg
DAILY
Yes
+/- HCTZ
No
Valsartan
(Diovan®)
20-40 mg DAILY 160 mg BID
Yes
+/- HCTZ
No
ARBs
• Use in patients intolerant to ACE-Is
• May be alternative in patients with ACE-I
associated angioedema
– Cases of patients with angioedema to ARB
• Similar precautions and monitoring as ACE-Is
Aldosterone Antagonists
AAs
Initial Dose
Goal Dose
TennCare
Exempt List
$4 Generic
Lists
Spironolactone
(Aldactone®)
12.5-25 mg DAILY
25 mg DAILY
No
Yes
Eplerenone
(Inspra®)
25 mg DAILY
50 mg DAILY
No
No
Aldosterone Antagonists
• Should be considered in NYHA II-IV
– NYHA II: prior CV hospitalization or elevated BNP
• Also following acute MI if EF < 40% and
patient with HF symptoms or DM
• SCr < 2.5 (men) or 2.0 (women), or GFR > 30
mL/min, K < 5.0 mEq/L
• Check SCr and K in 2-3 days and at 7 days
following initiation
• Decrease dose or discontinue if K > 5.5 mEq/L
Hydralazine/Isosorbide
Vasodilators
Initial Dose
Goal Dose
TennCare
Exempt List
$4 Generic
Lists
Hydralazine/
Isosorbide dinitrate
(Bidil®)
37.5/20 mg TID
75/40 mg TID
No
No
Hydralazine
(Apresoline®)
25-50 mg
3-4x DAILY
300 mg DAILY
divided 3-4x
Yes
Yes, only low
doses
Isosorbide dinitrate
(Isordil®)
20-30 mg
3-4x DAILY
120 mg DAILY
divided 3-4x
No
No
Hydralazine/Isosorbide
• Recommended in African American patients
who remain symptomatic despite ACE-Is/
ARBs, beta blockers, and aldosterone
antagonists
• May be used in patients intolerant to ACE-Is/
ARBS
• Titrate slowly
• Headache, dizziness, GI complaints
Digoxin
• May improve symptoms and decrease
hospitalizations
• Avoid in sinus/AV block unless pacemaker
• Goal level 0.5-0.9 ng/mL; 0.5-0.8 ng/mL preferred
• Adverse effects include arrhythmias, anorexia,
N/V, confusion, visual disturbances
• Increased toxicity with hypokalemia,
hypomagnesemia, hypothyroidism, impaired
renal function, lean body mass
• Potential for drug interactions
Digoxin
• Retrospective subgroup analysis of women in DIG trial
– Increase in mortality compared to men including death
from CV causes or worsening HF
– Unclear if due to slightly higher digoxin concentrations (0.9
ng/mL vs 0.8 ng/mL)
• Another retrospective analysis showed serum digoxin
level to be continuous variable associated with
mortality
• Recommended as add-on therapy to BBs in patients
with atrial fibrillation (A. fib)
• May be used in A. fib with RVR in decompensated HF
Diuretics
• Loop diuretics 1st line for fluid retention
• Patients may become intolerant of furosemide
and may have improved response to
bumetanide or torsemide
• May require addition of metolazone to
maintain euvolemia
• Must monitor carefully as add or increase
doses of BBs, ACE-Is/ARBs, aldosterone
antagonists
Pearls
• Consider HF medications in patients at risk in need of
additional HTN treatment
• Titrate slowly but get to goal doses
• May give once-daily blood pressure medications at
bedtime to decrease adverse effects
• Caution patients to hold doses of ACE-Is, ARBs,
aldosterone antagonists if significant N/V/D or
dehydration
• Monitor K carefully if diuretic dose decreased and
patient on ACE-I, ARB, or aldosterone antagonist
• ACE-I + ARB + aldosterone antagonist not
recommended
Management of Acute Exacerbation
• IV loop diuretics
• May increase diuretic dose, consider continuous
infusion, and/or add metolazone to achieve
diuretic response
• CO2 will increase d/t contraction alkalosis prior to
SCr/BUN trending up
– Signal to decrease dose to prevent AKI
• Maximize vasodilator therapy as BP tolerates
• Only decrease/hold other HF medications if
hypotension/decreased cardiac output
Refractory HF (Stage D)
• Short-term intravenous inotropes indicated in
cardiogenic shock to maintain perfusion
• Continuous inotropes may be used as “bridge”
to cardiac transplant or ventricular assist
device (VAD) therapy
• Long-term use reserved for palliative care
Inotropes
Inotrope
Dose (mcg/kg/min)
Halflife
CO
HR
SVR
PVR
Adverse
effects
Dobutamine
Stimulates beta 1 receptors leading to increased HR and contractility, little effect on beta
2 or alpha receptors
(Dobutrex®)
Initial: 2.5-5
Maintenance: 5-20
2-3
min
↑
↑
↓↔
↔
Tachyarrhythmias
Milrinone
Inhibits PDE-3 in cardiac and vascular tissue leading to increased cardiac contractility and
decreased vascular tone
(Primacor®)
Initial: 0.125-0.375
Maintenance: 0.375-0.75
2.5 h
↑
↑
↓
↓
Tachyarrhythmias
PDE-5 Inhibitors
• Sildenafil approved for use in pulmonary arterial
hypertension (Group 1)
• Inhibits PDE-5 leading to pulmonary vascular
relaxation
• Studied in HF patients with secondary pulmonary
hypertension (Group 2)
– 12 week study: increased peak VO2, improvement in
RVEF, improved QOL
– 6 month study: decreased PAP, increased peak VO2,
improved breathlessness score
Iron Deficiency and Anemia in HF
• Anemia and iron deficiency are comorbidities
in HF associated with adverse outcomes
• Iron deficiency in HF defined for study
purposes
– Ferritin < 100 ng/mL OR
– Ferritin 100-300 ng/mL and Tsat < 20%
• Prospective study found 37% of HF patients
(mean EF 26%) met criteria
• Intravenous iron regimens under study
FERRIC-HF and FAIR-HF
FERRIC-HF
• NYHA class II-III and iron deficiency as defined treated with
IV iron sucrose versus placebo
• Noted improvements in QOL and functional class
• Statistically significant increase in peak VO2 in patients with
anemia and IDA
FAIR-HF
• Similar to FERRIC-HF but patients received IV ferric
carboxymaltose
• Improvements in QOL, functional class and 6-minute walk
• No difference in hospitalizations or mortality at 24 weeks
No long-term data
Potential Algorithm
Omega 3 Fatty Acids
• Omega-3 polyunsaturated fatty acids (PUFA) may be
used as adjunctive therapy
• Decreased mortality observed in post-MI patients
receiving omega-3 PUFA 1 g
• Subgroup analysis showed greatest reduction in
patients with reduced EF
• GISSI-HF study compared omega-3 PUFA 1 g to placebo
– Decreased mortality 27% versus 29% in placebo
– CV death or hospitalization also decreased
• Safe and well-tolerated
Paradigm-HF Trial
• Evaluated angiotensin receptor-neprilysin inhibitor
(LCZ696) versus enalapril
• NYHA II-IV with EF < 40% randomized to LCZ696 or enalapril
10 mg bid
• Stopped early with median follow up of 27 months due to
benefit in LCZ696 group
– Death from any cause 17.0% vs 19.8% (p<0.001)
– Death from CV cause 13.3% vs 16.5% (p<0.001)
– Reduced risk of hospitalization by 21% (p<0.001)
• Increased rate of hypotension and nonserious angioedema
• Decreased proportion of renal impairment, hyperkalemia,
and cough
Questions?

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