We recommend an ACE inhibitor or an ARB and a beta-blocker, when appropriate, to slow the progression of HF pathophysiology. It is important to be aware of the potential adverse effects of certain beta-blockers in patients with HF. Only 3 beta-blockers are approved for use in this patient population in the United States—bisoprolol, carvedilol, and metoprolol succinate, which have been found to provide benefits that other beta-blockers do not.6,15
Stages C and D: Tx considerations and controversies
Treatment for patients at stage C should include all components of therapy for patients at stages A and B, but with a more aggressive use of pharmacotherapy ( TABLE 2 ). Patients with stage C HF, by definition, are symptomatic, and the ACC/AHA recommendations reflect concern about their increasingly compromised status. Thus, in addition to the use of ACE inhibitors or ARBs and beta-blockers, modest use of diuretics is recommended, as needed, for fluid volume control.6 Diuretics should be used judiciously, though, with ongoing evaluation to avoid the excessive loss of potassium and magnesium, which can lead to volume depletion and lethal arrhythmias. Limiting sodium consumption is an important dietary restriction for stage C patients.
Aldosterone antagonists may also be considered on a case-by-case basis for patients with stage C HF. Due to their potassium-sparing effects, aldosterone antagonists, used in conjunction with standard therapies, may have a positive effect on electrolyte balance. Potassium levels must be carefully monitored, however, and potassium supplementation reevaluated for patients who are put on an aldosterone antagonist.19
Digitalis may also be helpful in select patients who remain symptomatic despite maximal pharmacotherapy.20 While it does not affect mortality, digitalis has been shown to reduce hospitalizations.21
ACE inhibitor-ARB combination therapy, another possible treatment for advanced HF, remains controversial. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), detailed in “ACE inhibitors and ARBs: One or the other—not both” in the January 2009 issue of The Journal of Family Practice, evaluated use of this dual therapy; the trial was also designed to determine whether telmisartan (an ARB) is inferior to ramipril (an ACE inhibitor) in patients at high risk for vascular events.22 The researchers found that telmisartan is not, in fact, inferior to ramipril, and reported that for patients with HF, an ACE-ARB combination offers a potential benefit.
However, the clinical benefit of an ACE-ARB combination in this patient population was not clarified in this study, and may be potentially harmful. In the Valsartan Heart Failure Trial (ValHeFT), the combination of valsartan, an ARB, and an ACE inhibitor decreased hospitalizations but did not improve mortality.23 Indeed, an increase in mortality was found when an ACEARB combination was used in conjunction with beta-blockers. Because beta-blockers are indicated for routine use in patients with HF, this finding was of particular concern.
In a meta-analysis of randomized trials using both an ACE inhibitor and an ARB in patients with left ventricular dysfunction, researchers found a “marked” increase in adverse effects, including deteriorating renal function (RR=2.17), hyperkalemia (RR=4.87), and symptomatic hypotension (RR=1.05).24 Although an ACE-ARB combination may benefit a subset of patients with HF, it is best to initiate such treatment only with the guidance of an HF specialist.
TABLE 2
Treating heart failure: How the different drugs and devices rate
STAGE | PHARMACOTHERAPY | LOE | DEVICE/INTERVENTION | LOE |
---|---|---|---|---|
A | Treat BP per JNC 7 ACE inhibitor or ARB for patients with vascular disease or diabetes | A | None | N/A |
B | ACE inhibitor or ARB BB | A | None | N/A |
C | Routine use: Diuretics ACE inhibitor BB Select use: Aldosterone antagonist ARB Digitalis | A | Consider: Biventricular pacer or ICD or both | B |
D | Same as C | B | Consider: Heart transplant or LVAD; experimental protocols | C |
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BB, beta-blocker; BP, blood pressure; ICD, implantable cardioverter defibrillator; JNC 7, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; LOE, level of evidence; LVAD, left ventricular assist device. | ||||
Adapted from: Hunt SA, et al. Circulation. 2005.6 |
Beyond drug therapy: Assistive devices
Refractory end-stage HF requires a clear treatment plan, and should involve the recommendations of an HF specialist. Careful maintenance of fluid status is required, and an evaluation for cardiac transplantation may be considered.
A left ventricular assist device (LVAD) should also be considered for patients with an estimated 1-year mortality of >50%.6 LVADs are mechanical heart pumps that were initially utilized as a “bridge” to transplant, but are increasingly being used as a palliative alternative for severely ill patients.25