Best of heart failure

14 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 454 24.4.5 Angiotensin Receptor Blockers (ARB) ARB is an effective treatment in patients with CHF. In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study [ 27 ], 768 patients in NYHC II–IV and EF <40% received candesartan, candesar- tan plus enalapril, or enalapril alone for 43 weeks. Left ven- tricular cavity size increased less, and BNP levels decreased more with combination therapy compared to ARB or ACEI alone [ 69 ]. In the Evaluation of Losartan in the Elderly (ELITE) trial [ 83 ], 722 patients with EF ≤ 40%, ≥ 65 years of age, and in NYHC Class II–IV were included. The primary endpoint was death and/or hospital admission for heart failure and occurred at a rate of 9.4% in the losartan group compared to 13.2 in the captopril group (risk reduction 32%, p = 0.075). This risk reduction was primarily due to a decrease in all- cause mortality (4.8% versus 8.7%; risk reduction 46%, p = 0.035) with similar rates of hospital admissions in both groups (5.7 ). ELITE II [ 84 ] randomized 3152 patients aged 60 years or older with NYHC II–IV and ejection frac- tion of <40% to losartan ( n = 1578) titrated to 50 mg once daily or captopril ( n = 1574) titrated to 50 mg three times daily. ELITE II showed no differences in mortality between losartan and captopril and confirmed that ARB therapy can be a potential substitute to ACEI. The Valsartan in Heart Failure Trial (Val-HeFT) [ 85 ] ran- domized 5010 patients with heart failure of New York Heart Association (NYHA) Class II, III, or IV to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined endpoint of mortality and mor- bidity, defined as the incidence of cardiac arrest with resusci- tation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least 4 h. Mortality was similar in both groups, but the combined end- point of morbidity and mortality was reduced by 13.2% with valsartan ( p = 0.009), predominantly driven by a reduction in heart failure hospitalizations (13.8% versus 18.2%, p < 0.001). In patients intolerant to ACEI, valsartan (titrated to 160 mg twice daily) reduced both all-cause mortality and combined mortality and morbidity compared with placebo (17.3% versus 27.1%, p = 0.017 and 24.9% versus 42.5%, p < 0.001, respectively) [ 86 ]. In a substudy of this trial, val- sartan taken with either ACEI or beta blockers reversed left ventricular remodeling [ 87 ]. Of interest, in the Val-HeFT, valsartan with either a beta blocker or ACEIs showed a posi- tive effect on outcome [ 88 ], but an adverse effect in patients receiving both types of drugs [ 85 ]. This concern of adding an ARB to patients on both ACEI and beta blockers was not confirmed in the CHARM trial. The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) [ 86 ] was a randomized, double-blind, placebo-controlled, multi- center study in patients with NYHC Class II–IV. This trial had three complementary arms: CHARM-added, candesar- tan (titrated to 32 mg once daily) is added to an ACEI; CHARM-alternative, candesartan administered to patients who cannot tolerate ACEIs; and CHARM-preserved, can- desartan is administered to patients with preserved left ven- tricular function irrespective of whether they are on ACEI or not. In the CHARM-added and CHARM-alternative arms, patients with EF ≤ 40% were included. In the “over- all program” of this study [ 87 ], which included both pre- served and reduced left ventricular function, total mortality was not reduced compared to placebo. However, in a sub- group analysis of patients with symptomatic heart failure and reduced left ventricular function, candesartan signifi- cantly reduced all-cause mortality (28% versus 31%, p = 0.0018), cardiovascular death (22.8% versus 26.2%, p = 0.005), and CHF hospitalizations (22.5% versus 28.1%, p < 0.001) when added to standard therapies including ACEI, beta blockers, and aldosterone antagonists [ 88 ]. Candesartan also reduced progression to diabetes [ 89 ], sud- den cardiac death, and death from worsening heart failure in patients with symptomatic failure [ 86 ]. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) [ 90 ] randomized patients 0.5–10 days after an acute MI with reduced left ventricular function to valsartan (4909 patients) titrated to 160 mg twice a day, valsartan (80 mg twice a day) plus captopril (50 mg three times a day) (4885 patients), or captopril (4909 patients) alone titrated to 50 mg three times a day in addition to standard therapy. The primary endpoint of the study was all-cause mortality at a median follow-up of 24.7 months. Valsartan was equally effective compared to captopril in reducing all- cause mortality. Also combining valsartan with captopril increased the rate of adverse events without improving survival. In the Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan (OPTIMAAL), patients after an acute myocardial infarction were randomized to losartan versus captopril. The primary endpoint was reduc- tion in all-cause mortality at a mean follow-up of 2.7 years. A nonsignificant difference was seen in total mortality in favor of captopril (18% versus 16% in the losartan versus captopril, respectively, p = 0.07). However, there were sig- nificantly more cardiovascular deaths with losartan (15%) than with captopril (13%) ( p = 0.03) [ 91 ]. Losartan was bet- ter tolerated than captopril with fewer patients discontinuing their medications (17% versus 23%, p < 0.0001) [ 92 ]. An echocardiographic substudy of the OPTIMAAL trial has shown that both losartan and captopril improve systolic function after an acute MI, but the benefit is greater for cap- topril [ 93 ]. A growing body of evidence suggests that an ARB can be an alternative to an ACEI in patients with CHF [ 74 ]. N. W. Shammas