One RCT demonstrated the efficacy of ivabradine in reducing the composite endpoint of cardiovascular death or HF The benefit of ivabradine was driven by a reduction in HF hospitalization. The study included patients with HFrEF (NYHA class II-IV, albeit with only a modest representation of NYHA class IV HF) and left ventricular ejection fraction (LVEF) 35%, in sinus rhythm with a resting heart rate of 70 beats per minute. Patients enrolled included a small number with paroxysmal atrial fibrillation (<40% of the time) but otherwise in sinus rhythm and a small number experiencing ventricular pacing but with a predominant sinus rhythm. Those with a myocardial infarction within the preceding 2 months were excluded. Patients enrolled had been hospitalized for HF in the preceding 12 months and were on stable GDEM* for 4 weeks before initiation of ivabradine therapy. The target of ivabradine is heart rate slowing (the presumed benefit of action), but only 25% of patients studied were on optimal doses of beta-blocker therapy.9,139,140,155 Given the well-proven mortality benefits of beta-blocker therapy, it is important to initiate and up titrate these agents to target doses, as tolerated, before assessing the resting heart rate for consideration of Recommendations for Renin-Angiotensin System Inhibition With ACE Inhibitor or ARB or ARNI (Continued) COR LOE Recommendations Comment/Rationale *In other parts of the document, the term GDMT has been used to denote guideline-directed management and therapy. In this recommendation, however, the term GDEM has been used to denote this same concept in order to reflect the original wording of the recommendation that initially appeared in the 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. 10 Yancy et al 7.3.3. 