Congestive Heart Failure CHF
First Line Drugs
- CILAZAPRIL (C09AA08)
- CHLORTALIDONE (C03BA04)
Second Line Drugs
- DIGOXIN (C01AA05)
- LOSARTAN (C09CA01)
- CARVEDILOL (C07AG02)
Patients with impaired Ejection Fraction, first line
1. ACE inhibitors
cilazapril  0.5-2.5 mg, once daily $0.30-0.68/day
or lisinopril 5-20 mg, once daily $0.67-0.97/day
or ramipril 2.5-10 mg, once daily $0.75-0.95/day
-The effect of ACE inhibitors is assumed to be a class effect although data for ACE inhibitors other than captopril, cilazapril, enalapril, fosinopril, lisinopril, quinapril and ramipril are limited.
i. Thiazide and thiazide-like diuretics
hydrochlorothiazide 25-50 mg, once daily in am $0.01/day
or chlorthalidone 25-50 mg, once daily in am $0.01-0.02/day
or metolazone 2.5-10 mg, once daily in am $0.15-0.24/day
ii. If congestion is more serious, use loop diuretics
furosemide 20 mg, once daily; titrate to response(maximum 200 mg, bid) $0.01-0.08/day
or bumetanide 0.5 mg, once daily; titrate to response(maximum 5 mg, bid) $0.20-3.10/day
or ethacrynic acid 50 mg, once daily; titrate to response(maximum 100 mg, bid) $0.32-1.27/day
or torsemide 10 mg, once daily; titrate to response(maximum 100 mg, once daily) $0.86-4.76/day
1. If symptoms are uncontrolled by diuretics and ACE inhibitors despite increasing dose (even in patients with sinus rhythm) add:
digoxin 0.125-0.25 mg, once daily $0.09/day
-Digoxin does not reduce overall mortality from congestive heart failure but it does reduce the rate of admission to hospital both overall and for worsening heart failure.
-Digoxin is potentially more useful in patients with 1 or more of the following: S3, functional class III-IV or cardiomegaly on chest roentgenogram.
-An example of eccentric dosing is 8 am, noon and 4 pm. Administering doses at these intervals leaves a nitrate-free period of about 12 h.
2. If unable to use ACE inhibitors
i. Angiotensin II type 1 receptor antagonist
losartan 12.5 mg, once daily; titrate at weekly intervals to 25 mg, once daily and then 50 mg, once daily $0.55-1.10/day
(Addendum May 29, 2012 Cochrance Review ARB vs ACEI)
Twenty two studies evaluated the effects of ARBs in 17,900 patients with a LVEF 40% (mean 3.7 years). ARBs did not reduce total mortality (RR 1.02 [95% CI 0.93, 1.12]) or total morbidity as measured by total hospitalisations (RR 1.00 [95% CI 0.97, 1.05]) compared with placebo. Withdrawals due to adverse effects were higher with ARBs versus placebo when all patients were pooled irrespective of LVEF (RR 1.06 [95% CI 1.01, 1.12]).
AUTHORS' CONCLUSIONS: In patients with symptomatic HF and systolic dysfunction or with preserved ejection fraction, ARBs compared to placebo or ACEIs do not reduce total mortality or morbidity. ARBs are better tolerated than ACEIs but do not appear to be as safe and well tolerated as placebo in terms of withdrawals due to adverse effects. Adding an ARB in combination with an ACEI does not reduce total mortality or total hospital admission but increases withdrawals due to adverse effects compared with ACEI alone.
(Addendum High- dose losartan appeared superior in preventing deaths in heart failure patients)
Study lends support to titration to the higher dose drug unless limited by adverse effect, to achieve improved clinical outcomes in patients with heart failure and reduced LVEF. Lower dose losartan in CHF was no better and possibly worse than moderate dose ACE inhibitor in OPTIMAAL trial
Reference:Konstam MA et al, Effects of high-dose versus low-dose losartan on clinical outcomes inpatients with heart failure (HEAAL study): a randomized, double-blind trial. The Lancet; 374:1840-1848
ii. Combination of:
isosorbide dinitrate 20-40 mg, tid with eccentric dosing $0.10-0.19/day
hydralazine 25-75 mg, tid $0.49-1.25/day
3. For patients who remain symptomatic despite receiving diuretics, ACE inhibitors and digoxin, add:
carvedilol 3.125 mg, bid; increase over 2-10 weeks to 25 mg, bid $2.54/day
-Beta-blockers other than carvedilol may also be useful in congestive heart failure but further research is needed before they can be recommended.
-(Addendum Feb 5, 2013)The effect of beta-blockers on outcome in HF patients with reduced systolic LVEF who have AF is less than in those who have sinus rhythm. Ref http://heartfailure.onlinejacc.org/article.aspx?articleid=1568318
OTHER DRUGS to consider:
(I)Calcium Channel Blockers
Felodipine and amlodipine are safe, but do not reduce mortality or morbidity in patients with systolic HF.35 , They may be useful in select patients with persistent angina despite the use of beta-blockers (and nitrates) or in patients with uncontrolled hypertension despite the use of an ACEI, ARB, beta-blocker and a diuretic.
Avoid diltiazem and verapamil in patients with systolic HF because of their negative inotropic effects and nifedipine because of the lack of data.
Consider amiodarone to maintain sinus rhythm in select patients with atrial fibrillation. Amiodarone also reduces the frequency of repetitive ICD discharges. Consider dronedarone in select patients with mild and stable HF. It is contraindicated in patients with NYHA class IV or NYHA class II–III with a recent decompensation requiring hospitalisation or referral to a specialised heart failure clinic. The use of dronedarone doubled the risk of mortality in such patients in a randomised trial. Additional data are required to determine the safety and efficacy of dronedarone in patients with symptomatic HF.
Avoid all other antiarrhythmic drugs. Antiarrhythmics are not recommended to prevent sudden cardiac death because they do not reduce mortality. It should be emphasised that a strategy of maintaining sinus rhythm in patients with HF is not superior to ventricular rate control in patients with a history of atrial fibrillation.
(III)HMG CoA Reductase Inhibitors (Statins)
Although the benefit of statins in the primary and secondary prevention of coronary artery disease is well established, trials have suggested that the benefits of statins in patients with HF may be limited, even if they have coronary artery disease, Nevertheless, patients included in these trials were relatively older (mean age at baseline of 69 and 73 years) and presented with a baseline LDL cholesterol of only 3.2 mmol/L and 3.5 mmol/L, respectively. Consequently, it appears reasonable to continue treating younger patients and/or patients who are at high risk of cardiovascular events (recent myocardial infarction, diabetes and known vascular disease). Because these trials did not study the impact of statin discontinuation, it appears reasonable to continue the use of these agents in patients who are receiving them.
In patients with HF with PEF(Preserved Ejection Fraction), focus treatment on control of risk factors (hypertension, diabetes mellitus, ventricular rate in patients with supraventricular arrhythmias), volume status and decrease heart rate to optimize filling time. Trials have suggested that the chronic use of renin-angiotensin system modulators does not significantly reduce the risk of mortality in patients with HF with PEF. Nevertheless, these agents should be used to treat hypertension, particularly in patients with diabetes, left ventricular hypertrophy, nephropathy or coronary artery disease because of their established efficacy and end-organ protection in these patient populations. Beta-blockers are recommended in patients with CAD, prior MI, hypertension or atrial fibrillation to control ventricular rate. Diuretics should be used to optimize volume status. Verapamil or diltiazem may be considered to control the ventricular rate in patients with supraventricular arrhythmias or angina, in those who cannot tolerate a beta-blocker. Calcium channel blockers may also be considered in patients with hypertension.
Decompensated Heart Failure
Few large, randomized trials have been performed in patients with decompensated or acute HF. Intravenous loop diuretics are recommended in patients with signs and symptoms of fluid retention (e.g., furosemide 40–200 mg 2 or 3 times daily based on renal function or the patient’s usual dose of furosemide).
Use combinations of diuretics, or add a vasodilator such as nitroglycerin, nesiritide or nitroprusside for hospitalized patients who do not respond to intravenous furosemide. Although clinical guidelines recommend the use of nesiritide, a multicentre, randomized placebo-controlled trial demonstrated that nesiritide has only a modest benefit on dyspnea in patients with decompensated HF. The higher cost of nesiritide compared to nitroglycerin will likely limit its role in the treatment of patients with decompensated HF.44 Intravenous vasodilators with a loop diuretic can be used initially in patients with moderate to severe symptoms of pulmonary congestion or those with severe hypertension. Sublingual nitroglycerin can be given before intravenous nitroglycerin. Invasive monitoring is recommended when administering nitroprusside. Take care to prevent cyanide and thiocyanide toxicity with nitroprusside; avoid in patients with hepatic or renal failure.
In patients with low cardiac output, milrinone or dobutamine is indicated if the systolic blood pressure is >90 mm Hg, and dobutamine if the systolic blood pressure is <90 mm Hg.1 Limit the use of vasopressors (dopamine or norepinephrine) to patients with significant hypotension. Dosages of these agents are based on vital signs, clinical status, comorbidities and the treatment regimen of the patient. In select patients, invasive monitoring of hemodynamic parameters may be used to adjust the dose.
DIET and NUTRITION
(Addendum Nov 5, 2012 on low salt diet appears harmful!)
(Addendum Nov 22, 2011 based on http://www.e-therapeutics.ca)
Based on a trial that suggested a modest reduction of cardiovascular events with low-dose omega-3 polyunsaturated fatty acid (n-3 PUFA), some guidelines suggest that low-dose n-3 PUFA (1 g/day) may be considered in patients with mild to moderate HF.4,34Whether higher doses of n-3 PUFA are more effective is unknown, but doses of more than 3 g/day have been associated with excessive bleeding.34 Monitor the INR in patients receiving warfarin following n-3 PUFA initiation. Because n-3 PUFA are food supplements, patients should consult their pharmacist to help in the selection of a reliable n-3 PUFA brand that most closely matches the formulation studied in HF (850–882 mg eicosapentaenoic acid and docosahexaenoic acid as ethyl esters in an average ratio of 1:1.2).