Ivabradine is a new therapeutic agent that selectively inhibits the If current in the sinoatrial node, providing heart rate reduction. One RCT demonstrated the efficacy of ivabradine in reducing the composite endpoint of cardiovascular death or HF hospitalization.38 The benefit of ivabradine was driven by a reduction in HF hospitalization. The study included patients with HFrEF (New York Heart Association [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 bpm. 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.20 22,38 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 ivabradine initiation.38 III: Harm C-EO ARNI should not be administered to patients with a history of angioedema. N/A Omapatrilat, a neprilysin inhibitor (as well as an ACE inhibitor and aminopeptidase P inhibitor), was associated with a higher frequency of angioedema than that seen with enalapril in an RCT of patients with HFrEF.31 In a very large RCT of hypertensive patients, ompatrilat was associated with a 3-fold increased risk of angioedema as compared with Blacks and smokers were particularly at risk. 