Additional Benefits Versus Practicalities of Beta-Blocker Use in CHF Patients: The 'Some Is Better Than None' Rule

Graham Archard

Disclosures

Br J Cardiol. 2005;12(4):313-317. 

In This Article

The NICE Guidelines

In light of the growing body of evidence for the beneficial use of beta blockers, the NICE guidelines for treatment of chronic heart failure in the UK recommend that beta blockers should be prescribed for all patients with stable chronic heart failure who are currently receiving ACE inhibitors and diuretic treatment.[18] Their association with reduced mortality means that treatment with beta blockers is recommended even in the absence of persistent symptoms. The guidelines also give advice regarding more specific aspects of beta blockade:

There are only two beta blockers currently licensed for chronic heart failure in the UK, carvedilol (Eucardic[®]) and bisoprolol (Cardicor[®], Emcor[®], Monocor[®]). Carvedilol is a non-selective 'third generation' beta blocker that acts on the α1, β1 and β2 receptors in the heart and peripheral vasculature. By contrast, biso-prolol is specific for the β1 receptors in the heart. Both drugs have been shown to have a mortality risk benefit[8,10] but no trial has directly compared the efficacy of both agents. There is some evidence that the non-selective agents might be more beneficial because they exhibit a wider degree of adrenergic blockade than the selective drugs.[19] However, cardioselective agents may be safer for use in patients with obstructive lung diseases such as asthma and chronic obstructive pulmonary disease since they are less likely to cause bronchospasm.[20]

Careful initiation of beta-blocker treatment is essential because there can be a mild reduction in systolic performance at the onset of therapy with these agents.[21,22] This is an important concern for patients who already have an inefficient heart. All patients of any NYHA class who are stable on ACE inhibitors and diuretics should be considered for treatment with beta blockers. Particular caution is needed for those who have symptomatic or asymptomatic bradycardia, bronchospastic disease or advanced heart block but beta blockers should be withheld only from those patients with decompensated heart failure, significant fluid retention or those who are in hospital due to heart failure treatment. Contrary to initial thinking, people with diabetes are at no greater risk from betablocker treatment than non-diabetics.[23] The guidelines also suggest that the benefits of treatment should be explained to the patient, emphasising that treatment is given to prevent worsening of heart failure (thus improving survival) as much as to control symptoms.

The NICE guidelines recommend that beta blockade is started at low levels and titrated upwards towards a target dose (for which a benefit has been shown in clinical trials). It is suggested that the dose should be doubled no less than every two weeks until optimum dosage is achieved ( Table 1 ). In this way, the adverse effects of treatment are given time to resolve before the body is challenged again. If this dosage cannot be achieved, the guidelines recommend treatment with the maximum tolerated dose. After each titration, the patient's heart rate, blood pressure and clinical status should be monitored. Patients should be advised that they may experience a temporary deterioration in their symptoms during the titration phase and that this should be reported to their physician.

NICE guidelines estimate that 20-30% of patients experience symptomatic deterioration of their condition during the uptitration phase of treatment. The guidelines detail a number of practical measures to manage the adverse effects of beta blockers (based on the recommendations of McMurray et al., 2001) and improve the likelihood of successful treatment.[24]

For worsening congestion, the first course of action is to double the dose of diuretic. Only if this is unsuccessful should the dose of beta blocker be reduced. In the case of marked fatigue or bradycardia, it is suggested that the beta-blocker dose is halved. However, this is rarely necessary. Asymptomatic hypotension does not usually require a change in therapy but if the patient experiences dizziness, light-headedness or confusion, discontinuation of other drugs such as nitrates, calcium channel blockers and other vasodilators should be considered. If there are no signs of congestion, the diuretic dose can be reduced.

With all these treatment modifications, patients should be reviewed after one to two weeks and specialist advice should be sought if there is no improvement. It is important never to discontinue beta-blocker treatment suddenly as there is a risk of a 'rebound' effect.

Despite following this advice there will undoubtedly be many patients, particularly those who are older and/or have a more severe class of heart failure, who cannot tolerate target drug doses.[25] Fortunately, these patients are still able to benefit from lower levels of beta blockade: Results from the CIBIS II trial showed that bisoprolol reduced all-cause mortality at low doses as well as at the higher target doses.[25] A dose-dependent response with improvements in left ventricular function and survival was also seen in patients receiving carvedilol.[26,27] Thus, it is important to treat all patients with beta blockers, even if the target dose cannot be reached.

Economic analysis of drug treatment programme is a complex issue. It is almost always impossible to compare Results from different studies due to the differing Methods and parameters used in the analyses. In addition, cost analyses, in contrast to efficacy data, are usually based on one healthcare system and the Results are therefore only applicable in one country. Other concerns involve the period of analysis, which varies between studies (some are concerned with the trial period alone and others extrapolate data to include projected costs and benefits) and the time when the study was carried out (studies conducted at different times cannot be compared).

The NICE guidelines identified six trials that were of adequate quality to evaluate the economic benefits of beta-blocker usage. No study has been carried out to compare bisoprolol with carvedilol treatment directly.

The cost-effectiveness of treatment with bisoprolol in the UK was investigated in a study by Varney et al. which used data from the CIBIS I and II trials.[28] The study included two periods of economic analysis; the first examined the 1.3-year trial duration while the second extrapolated data over five years. Cost benefits were mainly observed by the reduction of hospitalization rates among patients receiving bisoprolol. For the best-case scenario, there was even an overall cost reduction with treatment. The author concluded that treatment with bisoprolol (on top of treatment with ACE inhibitors) is an economically attractive therapy.

Potential economic benefits of carvedilol were examined by a US study that used a hypothetical cohort of patients receiving carvedilol (in addition to conventional therapy with ACE inhibitors and digoxin) compared with patients receiving conventional therapy alone.[29] The model was based on data from the US Carvedilol Heart Failure Trials Program and other sources. Cost-effectiveness ratios were high in the limited-benefit scenario. However, this may be due to the conservative benefits associated with the short (six-month) period of study and the high carvedilol acquisition costs.

Carvedilol is associated with significantly higher drug acquisition costs than bisoprolol because of its higher target dose.[30] Treating with bisoprolol only costs between 20% and 39% of the amount spent treating with carvedilol at target doses. However, cost-effectiveness is concerned not only with drug acquisition costs but must take into account patient outcomes, adverse side effects and resource usage; for these there are no available data.

Beta Blockers in General Practice

Despite the NICE guidance and the evidence behind it, several studies have shown that beta blockers are underprescribed in general practice.

The IMPROVEMENT of heart failure programme conducted an international survey across 15 countries between September 1999 and May 2000. A total of 1,363 primary care physicians were questioned about the treatment of 11,062 patients.[31] Equal priority was given to symptoms and prognosis, and most physicians were aware of the benefits of treatment with beta blockers and ACE inhibitors. Despite this, only 34% of patients were prescribed a beta blocker and 20% were prescribed a beta blocker in combination with an ACE inhibitor. Other studies from countries across Europe, North America and Australia show that this underuse of beta blockers is not a problem confined to the UK.[32,33,34,35]

Physician resistance to prescribing beta blockers for the treatment of heart failure is likely to be due to many factors. First, treatment with beta blockers is often counterintuitive, with many GPs having been taught in medical school that beta blockers precipitate heart failure. Second, patient followup is perceived to be complex and many practitioners are concerned about adverse events during the early stages of treatment. Third, reluctance to use these agents may come from uncertainty in the diagnosis of heart failure.[36,37] In order to address these issues, it might be beneficial to provide GPs with better information on current treatment strategies and to provide specialist support and advice for the interpretation of test Results and the planning of treatment programmes.

It is true that there are some circumstances in which the use of beta blockers in primary care should be avoided. Patients with asymptomatic or symptomatic bradycardia (heart rate < 60 beats per minute), advanced heart block that is not managed with a pacemaker, or a history of asthma or chronic obstructive pulmonary disease should only receive beta blocker therapy with extreme caution and under specialist supervision. These patients should always be referred to a specialist for initiation of beta-blocker therapy.

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