BEYOND THE GUIDELINES - NEW OPTIONS FOR TREATING HEART FAILURE IN 2015
Maryl R. Johnson, M.D., University of Wisconsin, Madison, Wisconsin, USA
The updated ACCF/AHA Guideline for the Management of Heart Failure is not even 2 years old, however, trials have suggested new potential treatment options for heart failure with reduced ejection fraction (HFrEF). Two of these trials will be reviewed. Resting tachycardia is a poor prognostic factor in HFrEF pts. Indeed, beta-blockers may improve HFrEF outcomes in part by decreasing heart rate. The SHIFT trial evaluated ivabradine (inhibitor of If current in the sinoatrial node) in HFrEF pts with LVEF <35%, in sinus rhythm with heart rate >70, and a HF hospitalization in the previous year on guideline directed medical therapy (GDMT), including a beta-blocker if tolerated. At 22.9 months follow-up, 24% of ivabradine vs 29% of placebo pts reached the primary endpoint of cardiovascular death or HF hospitalization (HR 0.82, p<0.0001). Ivabradine caused fewer serious adverse events, but more bradycardia and visual side effects. SHIFT suggests that ivabradine is beneficial when the heart rate remains >70 in HFrEF pts on GDMT. The PARADIGM-HF Trial evaluated the combined angiotensin receptor-neprilysin inhibitor LCZ696 (valsartan-sacubitril) vs enalapril in class II-IV HFrEF pts with LVEF <40%. The trial was stopped after 27 months when the boundary for benefit with LCZ696 was crossed. The primary outcome (cardiovascular death or first HF hospitalization) occurred in 21.8% of LCZ696 vs 26.5% of enalapril pts (HR .80, P<0.001). LCZ696 also decreased mortality, cardiovascular death, and HF hospitalization. LCZ696 produced more hypotension, but less renal impairment, hyperkalemia and cough. Although the study was met with enthusiastic acclaim for the benefits of LCZ696, concerns have been raised about the trialís enalapril dose (10 mg bid) and the fact that 70% of pts had class II HF. The exact role of ivabradine and LCZ696 in future HFrEF therapy remains to be determined.