Drug category	Clinical pearls
ACE inhibitors/ARBs	Class effect. ACE inhibitors appear to exhibit a class effect. All members of this class may be equally effective.
	Contraindications. ACE inhibitors and ARBs may cause hyperkalemia in the presence of renal failure and should be avoided or used with caution in patients with a creatinine level of more than 2.5 mg per dL (221 μmol per L), a glomerular filtration rate of less than 30 mL per minute per 1.73 m2, or a potassium level of more than 5 mEq per L (5 mmol per L). Both drug classes are contraindicated in pregnant women and in patients with bilateral renal artery stenosis, unilateral renal artery stenosis and a solitary kidney, or allergies. Angioedema occurs rarely with either drug class.
ARB/neprilysin inhibitor	Contraindications. An ARB/neprilysin inhibitor should not be used concomitantly with ACE inhibitors or ARBs. It may cause hypotension or rarely angioedema. Precautions appropriate for ARBs related to concerns for hyperkalemia and renal failure also apply to the ARB/neprilysin inhibitor.
Beta blockers	Add when stable. Beta blockers may be used in patients with heart failure due to systolic dysfunction who do not have contraindications. They should be added when patients are stable to stop the progression of the disease. They are not used as rescue therapy for patients who are decompensating.
	Dosing. Start at a low dose, and double the dose every two to four weeks as tolerated until the target dosage is reached (see Table 3 for dosing). Stop titration if the patient is intolerant of higher doses.
	Absolute contraindications are heart block, bradycardia, and severe reversible airway disease.
	Relative contraindications are dyspnea at rest with signs of congestion or hemodynamic instability. Once these issues have resolved, beta blockers may be added to the chronic regimen.
Aldosterone antagonists	Hyperkalemia. The risk of hyperkalemia may be significant. These risks can be minimized by avoiding use in patients with a glomerular filtration rate of less than 30 mL per minute per 1.73 m2 or a creatinine level of more than 2.5 mg per dL, and by ensuring appropriate patient selection before initiating therapy (Table 2). Electrolytes must be monitored closely, as was done in clinical trials: monitor electrolytes when medication changes are made five to seven days after a dose change, and again after 30 days. A potassium elevation of more than 5 mEq per L should prompt a dose reduction or drug discontinuation.
Isosorbide dinitrate and hydralazine	Dosing. These medications are available as a fixed-dose combination (Bidil) or as individual generic components. Clinical trials were performed using isosorbide dinitrate. Isosorbide mononitrate is dosed daily and is more convenient. Evidence of clinical equivalence of the mononitrate form is based on expert opinion.
	Contraindications. These medications cannot be used concomitantly with phosphodiesterase inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra).
Ivabradine (Corlanor)	Initiation. It is used in patients with persistent symptoms and a heart rate of more than 70 beats per minute despite maximally tolerated or target dosage of beta-blocker therapy.
	Contraindication. It should not be used in patients with atrial fibrillation.
Diuretics	Background therapy. Although not specifically tested in clinical trials, diuretics should be used as needed for volume overload. Diuretics were consistently part of background therapy in all published placebo-controlled mortality trials of symptomatic patients in which ACE inhibitors, beta blockers, and aldosterone antagonists were tested.
Combining drugs	Starting other drugs. The therapy described in Table 2 is the desired end point for patients with the indicated symptoms and history. No data are available to indicate how best to introduce these medications. All of the major trials added beta blockers or spironolactone to background therapy of ACE inhibitors, diuretics, and sometimes digoxin.
	Electrolytes and renal function. Many of the medications appropriate for heart failure (ACE inhibitors, ARBs, aldosterone antagonists, digoxin) can affect potassium levels or can be affected by potassium levels and renal function. Vigilant monitoring is required.
	Discontinuation. ACE inhibitors, beta blockers, spironolactone, and ARBs should not be discontinued if symptoms improve because they slow disease progression and decrease mortality.
Referral	Consider referral for diagnostic procedures, ventricular arrhythmias, revascularization procedures, valvular heart disease, worsening or refractory heart failure, or consideration for transplantation.