1 No relevant financial relationships to discloseMending 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
2 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
3 Prevention Treat hypertension CAD/AtherosclerosisLong-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 % 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)
4 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
5 Diabetes and HF Pioglitazone (Actos®) DPP-4 inhibitorsIncrease 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
6 Medications to (Ideally) Avoid in HFNon-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®)
7 Optimize Standard TherapyTitrate to goal HF doses Beta blockers ACE-Is ARBs Aldosterone antagonists Hydralazine/Isosorbide Digoxin
8 Beta Blockers Avoid abrupt withdrawal HF approved BB Initial doseGoal dose TennCare Exempt List $4 Generic Lists Carvedilol (Coreg®) 3.125 mg BID 25 mg BID (<85 kg) 50 mg BID (>85 kg) Yes Metoprolol succinate (Toprol XL®) 12.5 mg DAILY 200 mg DAILY No Bisoprolol (Zebeta®) 2.5 mg DAILY 10 mg DAILY Yes, with HCTZ Avoid abrupt withdrawal
9 Beta Blockers Carvedilol Metoprolol succinate Improved BP controlUsually improved tolerability compared to metoprolol in regards to fatigue/depressive adverse effects Usually tolerated in COPD (>asthma) unless severe 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
10 ACE-Inhibitors ACE-Is Initial Dose Goal Dose TennCare Exempt List$4 Generic Lists Captopril (Capoten®) 6.25 mg TID 50 mg TID No Enalapril (Vasotec®) 2.5 mg BID 10-20 mg BID Yes, with HCTZ Benazepril (Lotensin®) 5-10 mg DAILY 40-80 mg DAILY or divided BID Yes Lisinopril (Zestril®) 2.5-5 mg DAILY 20-40 mg DAILY +/- HCTZ Perindopril (Aceon®) 2 mg DAILY 8-16 mg DAILY Quinapril (Accupril®) 5 mg BID 20 mg BID Ramipril (Altace®) mg DAILY 10 mg DAILY
11 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
12 ARBs ARBs Initial Dose Goal Dose TennCare Exempt List $4 Generic ListsCandesartan (Atacand®) 4-8 mg DAILY 32 mg DAILY Yes No Losartan (Cozaar®) 25-50 mg DAILY mg DAILY +/- HCTZ Valsartan (Diovan®) 20-40 mg DAILY 160 mg BID
13 ARBs Use in patients intolerant to ACE-IsMay be alternative in patients with ACE-I associated angioedema Cases of patients with angioedema to ARB Similar precautions and monitoring as ACE-Is
14 Aldosterone AntagonistsAAs Initial Dose Goal Dose TennCare Exempt List $4 Generic Lists Spironolactone (Aldactone®) mg DAILY 25 mg DAILY No Yes Eplerenone (Inspra®) 50 mg DAILY
15 Aldosterone AntagonistsShould 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
16 Hydralazine/IsosorbideVasodilators Initial Dose Goal Dose TennCare Exempt List $4 Generic Lists Hydralazine/ Isosorbide dinitrate (Bidil®) 37.5/20 mg TID 75/40 mg TID No Hydralazine (Apresoline®) 25-50 mg 3-4x DAILY 300 mg DAILY divided 3-4x Yes Yes, only low doses (Isordil®) 20-30 mg 120 mg DAILY divided 3-4x
17 Hydralazine/IsosorbideRecommended 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
18 Digoxin May improve symptoms and decrease hospitalizationsAvoid in sinus/AV block unless pacemaker Goal level ng/mL; 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
19 Digoxin Retrospective subgroup analysis of women in DIG trialIncrease 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
20 Diuretics Loop diuretics 1st line for fluid retentionPatients 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
21 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
22 Management of Acute ExacerbationIV 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
23 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
24 Inotropes Inotrope Dose (mcg/kg/min) Half-life CO HR SVR PVRAdverse 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 ↑ ↓↔ ↔ Tachy-arrhythmias Milrinone Inhibits PDE-3 in cardiac and vascular tissue leading to increased cardiac contractility and decreased vascular tone (Primacor®) Initial: Maintenance: 2.5 h ↓
25 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
26 Iron Deficiency and Anemia in HFAnemia 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 ng/mL and Tsat < 20% Prospective study found 37% of HF patients (mean EF 26%) met criteria Intravenous iron regimens under study
27 FERRIC-HF and FAIR-HF FERRIC-HFNYHA 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
28 Potential Algorithm
29 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
30 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
31 Questions?