(Level of Evidence: B) 6.3.2.6. HYDRALAZINE AND ISOSORBIDE DINITRATE CLASS I 1. The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated (179,180). (Level of Evidence: A) CLASS IIa 1. A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypoten- sion, or renal insuf ciency, unless contraindicated (188). (Level of Evidence: B) See Table 13 for a summary of the treatment bene t of GDMT in HFrEF. CLASS IIa 1. Digoxin can be bene cial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF (202 209). (Level of Evidence: B) 6.3.2.8. OTHER DRUG TREATMENT CLASS I 1. Patients with chronic HF with permanent/persistent/ paroxysmal atrial brillation (AF) and an additional risk factor for cardioembolic stroke (history of hyper- tension, diabetes mellitus, previous stroke or transient ischemic attack, or 75 years of age) should receive chronic anticoagulant therapy* (210 216). (Level of Evidence: A) 2. The selection of an anticoagulant agent (warfarin, dabiga- tran, apixaban, or rivaroxaban) for permanent/persistent/ paroxysmal AF should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including time in the international normalized ratio thera- peutic range if the patient has been taking warfarin. (Level of Evidence: C) CLASS IIa 1. Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but are without an additional risk factor for cardioembolic stroke* (211 213,217 219). (Level of Evidence: B) CLASS III: NO BENEFIT 1. 