Best of heart failure

16 clear reasons, and they are stem. Recently, the advent inhibitor (ARNI) sacubi- rmacologic approach that al endopeptidase enzyme concomitantly blocks the ith valsartan). of ARNI with ACEI to rtality and Morbidity in tudy [ 31 ], a double-blind, patients with Class II–IV tion of 40% or less were itril/valsartan (at a dose of ectively) or enalapril (at a rimary outcome of death rt failure rehospitalization ARNI arm (21.8%) com- 01). Cardiovascular death % CI, 0.71; 0.89)) and risk n by 21% (HR 0.79 (95% lity was reduced by 16% HR 0.84 (95% CI, 0.76; y stopped because of the en compared to ACEI. ere reported in more than study, and these included gh, dizziness, and renal dema was also higher in pared to enalapril (0.5% in the black population). be encountered more fre- double-blind period of by a single-blind run-in ed if they could not toler- I. en tested in CHF patients . These include endothelin agents, and growth hor- terventions that modulate he neprilysin enzyme (in only proven treatment to patients with congestive t in treating patients with bradine, an HCN channel n normal sinus rhythm and or on maximum tolerable was tested in The Systolic inhibitor ivabradine Trial 505 patients with chronic bradine versus placebo on t. Patients had to be in rt rate of more or equal ss or equal 35%, and have N. W. Shammas 456 In the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) study 991 patients with chronic heart failure in NYHC II–IV and EF ≤ 40% were enrolled in a double-blind, randomized, placebo- controlled study of metoprolol CR/XL versus placebo [ 101 ]. All-cause mortality and sudden death were reduced by 34% ( p = 0.00009) and 41% ( p = 0.0002) in the metoprolol group. Also, metoprolol CR/XL reduced the number of hospitaliza- tions due to worsening heart failure ( p < 0.001) and number of days in hospital due to worsening heart failure ( p < 0.001). In post-MI patients with symptomatic CHF and an EF ≤ 40% and receiving contemporary management, metoprolol CR/ XL reduced total mortality by 40% ( p = 0.0004) and sudden death by 50% ( p = 0.0004) [ 109 ]. The Cardiac Insufficiency Bisoprolol II (CIBS-II) study was a double-blind, placebo-controlled trial in Europe that enrolled 2647 symptomatic patient with Class III or IV heart failure and an EF ≤ 35% randomized to bisoprolol or pla- cebo. At 1.3 years, all-cause mortality and sudden death were reduced by 34% ( p < 0.0001) and 44% ( p = 0.0011), respectively, with bisoprolol. Also, bisoprolol resulted in fewer hospital admissions per patient hospitalized, fewer hospital admissions overall, and fewer days spent in hospital or intensive care unit leading to a reduction in the cost of care by 5–10% compared to placebo [ 110 ]. The Carvedilol Or Metoprolol European Trial (COMET) [ 111 , 112 ] is the only randomized trial that compared two beta blockers in a randomized, double-blind study in the manage- ment of CHF patients. 3029 patients with Class II–IV heart failure were recruited at 317 centers in 15 European countries. At 58 months, there was a 17% reduction in mortality with carvedilol compared to metoprolol tartrate ( p = 0.0017). Recently, carvedilol (6.25–25 mg twice daily) was also shown in The Glycemic Effects in Diabetes Mellitus: Carvedilol- Metoprolol Comparison in Hypertensives (GEMINI) study not to alter glycemic control in diabetics when compared to metoprolol tartrate (50–200 mg twice a day). Furthermore, it did i prove some components of the metabolic syndrome such as improving insulin sensitivity [ 113 ]. Currently recommended beta blockers in the management of CHF are carvedilol, metoprolol succinate, and bisoprolol [ 74 ]. Adherence to the use of beta blockade is of paramount importance to reduce the economic burden of CHF. Beta blockers are currently underutilized in patients with CHF [ 114 ], and continued educational efforts are needed to pro- mote guidelines in heart failure management. Aggressive titration of beta blockers is needed in patients with CHF. Higher levels of beta blockade andACEI are asso- ciated with better improvement of ejection fraction and greater reductions in cardiovascular hospitalizations [ 115 – 117 ]. In a substudy of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial, the composite endpoint of mortality or hospitalization decreased incremen- tally with the use of high-dose ACE inhibitors ( n = 475) (adjusted odds ratio (aOR) 0.93; p = NS), high-dose ACE inhibitors plus beta blockers ( n = 72) (aOR 0.89; p = NS), and high-doseACE inhibitors plus beta blockers plus digoxin ( n = 77) (aOR 0.47; p = 0.006) compared with low-dose ACE inhibitors ( n = 471) [ 117 ]. A stepwise approach in titration of beta blockade is generally followed with an increase in the dose every 2 weeks as tolerated until achieving the maxi- mum tolerable dose. 24.4.8 Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure The natriuretic peptide (NP) system counter-regulates the activation of the RAAS and the SNS. Recently, the angioten- sin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was introduced to inhibit the neutral endopeptidase enzyme neprilysin (with sacubitril) and concomitantly blocks the adverse effects of angiotensin II (with valsartan). In the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study [ 31 ], ARNI reduced the primary outcome of death from cardiovascular causes or heart failure rehospitalization (21.8%) when compared to ACEI (26.5%) ( p < 0.001). The individual endpoint of cardiovascular death was reduced by 20% (HR 0.80 (95% CI, 0.71; 0.89)), the risk of first heart failure hospitalization by 21% (HR 0.79 (95% CI, 0.71; 0.89)), and total mortality by 16% (absolute risk reduction 2.8%) (HR 0.84 (95% CI, 0.76; 0.93)). Current ACC/AHA/HFSA guidelines [ 118 ] consider ARNI as a Class I indication for treating patients with congestive heart failure and are preferred over an ACEI to further reduce mortality. 24.4.9 HCN Channel Blocker in Heart Failure Ivabradine, an HCN channel blocker was recently introduced to reduce heart failure hospitalization. It is indicated in patients in normal sinus rhythm and who are intolerant to beta blocker or on maximum tolerable dose of a beta blocker. Ivabradine was tested in The Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) [ 33 ]. It included patients in normal sinus rhythm with a heart rate of more or equal to 70 bpm, NYHC Class II–IV, EF less or equal to 35%, and have been hospitalized with heart failure in the past 12 months. Ivabradine significantly reduced the relative risk of hospitalization for worsening HF or CV death (RRR 18%, p < 0.0001); the significance is driven mostly by a reduction of rehospitalization. N. W. Shammas