How does carvedilol help chf

Carvedilol was generally well tolerated in patients with CHF. Adverse events associated with the alpha- and beta-blocking effects of the drug occurred more commonly with carvedilol than with placebo, whereas placebo recipients were more likely to experience worsening heart failure. In conclusion, carvedilol blocks beta 1 -, beta 2 - and alpha 1 -adrenoceptors and has a unique pharmacological profile.

Israel: G. Avinader, A. Caspi, A. Darausha, D. David, Y. Kishon, E. Klainman, B. Lewis, A. Marmor, M. Mitelman, M. Omary, L.

Reisin, T. Rosenfeld, S. Shasha, Z. Vered, R. Italy: E. Arosio, A. Branzi, C. Campana, M. Casaccia, L. Dei Cas, A. Di Lenarda, P. Fioretti, M. Frigerio, A. L'Abbate, M. Lithuania: A. Kibarskis, P. Serpytis, D. Vasiliauskas, P. Mexico: N. The Netherlands: R. Breedveld, J. Cornel, M. Daniels, P.

Dunselman, B. Hamer, L. Linssen, A. Maas, P. Twisk, A. Poland: L. Ceremuzynski, A. Cieslinski, M. Dalkowski, J. Dubiel, B. Filipek, H. Halaczkiewicz, M. Janion, K. Kawecka-Jaszcz, M. Krzeminska-Pakula, B. Kusnierz, K. Loboz-Grudzien, A. Malinski, T. Mandecki, W. Musial, W. Piotrowski, W. Pluta, W. Prastowski, W. Ruminski, A. Rynkiewicz, W. Smielak-Korombel, M. Tendera, R. Trojnar, M. Ujda, J.

Wodniecki, K. Wrabec, M. Portugal: M. Carrageta, R. Russia: G. Arutyunov, R. Charchoglian, A. Gruzdev, A. Ivleva, Y. Karpov, V. Kostenko, V. Mareev, V. Moisejev, L. Oblinskaya, V. Orlov, N. Perepech, E. Shlyhatkho, B. Sidorenko, A. Smirnov, A. Starodubsev, G. South Africa: P. Jordaan, P. Manga, D. Naidoo, I. Radevski, N. Switzerland: B. Caduff, P. Mohacsi, C. Ukraine : E. Amosova, G.

Dzyak, G. Knyshov, V. Kovalenko, V. Netyazhenko, S. Pavlyk, N. Seredjuk, Y. Serenko, L. Voronkov, A. United States : K. Aaronson, W. Abraham, J. Alexander, J. Allen, J. Anderson, J. Bergin, P. Berman, P. Binkley, N. Bittar, J. Bowers, L. Brookfield, J. Caplan, P. Carson, E. Carter, L. Christie, D. Chromsky, M. Cishek, V. Corrigan, M. Costanza, C. Curry, J. Davia, P. Deedwania, E. In most cases, however, ACE inhibitor therapy should be initiated and stabilized before the introduction of carvedilol therapy.

Finally, it is important to remember that, initially, beta-blocker therapy causes negative inotropic and chronotropic effects while the improvements in left ventricular function develop over time.

Therefore, patients hospitalized for heart failure, those in a fluid-overload state and those who are symptomatically hypotensive should not be given carvedilol. The starting dosage of carvedilol is 3. This dosage is the same regardless of the patient's age or weight. Because food slows the rate but not the extent of absorption, carvedilol should be taken with food to reduce the incidence of orthostatic hypotension. Patients should be observed in the physician's office for adverse reactions, especially dizziness, light-headedness and hypotension, for one hour after the first dose and again after each dosage increase.

Blood pressure should be measured with the patient standing. Patients should be instructed to weigh themselves every day and to contact their physician immediately if they experience a weight gain of 0. If, after two weeks, the initial dosage of carvedilol has been well-tolerated, it should be doubled. The dosage should be doubled every two weeks to the maximum dosage or the highest tolerated dosage. The maximum recommended dosage for carvedilol is 25 mg twice daily in patients weighing less than 85 kg lb and 50 mg twice daily in patients weighing 85 kg lb or more.

This dosage is the same regardless of the age or weight of the patient. Carvedilol should be taken with food. Patient should be observed in the office for one hour after initial dose is given. If previous dosage was well-tolerated, dosage should be doubled every two weeks to the maximum dosage or the highest tolerated dosage. Patient should be observed in the office for one hour after every dosage adjustment. Patient should be weighed daily. Any weight gain of 0.

Blood pressure measurements should be taken with the patient standing. Parameters of glycemic and lipid control should be monitored, and medicines should be adjusted appropriately. Therapy with ACE inhibitors should be initiated and stabilized before the introduction of carvedilol therapy. Patients should not be in the hospital for heart failure or in a fluid-overload state.

Bronchial asthma or related bronchospastic conditions; decompensated NYHA functional class IV heart failure requiring intravenous inotropic therapy; should not be used in patients with severe hepatic impairment, severe bradycardia, second-or third-degree arteriovenous block or sick sinus syndrome without a pacemaker, or in patients with a known hypersensitivity to carvedilol. May affect lipid and blood sugar levels. May mask signs or symptoms of hypoglycemia and hyperthyroidism. Should be used with caution in patients with peripheral vascular disease.

Decrease diuretic, vasodilator or ACE inhibitor therapy; if symptoms persist, decrease carvedilol dosage. Increase diuretic therapy; if signs and symptoms persist, decrease carvedilol dosage. It may also be necessary, based on clinical signs and symptoms, to adjust the dosages of the patient's other heart failure medications when carvedilol is introduced. When patients have signs and symptoms of excessive vasodilation, such as dizziness, lightheadedness or orthostatic hypotension, consideration should be given to decreasing diuretic, vasodilator or ACE inhibitor dosages.

If these signs and symptoms persist, the dosage of carvedilol should be decreased. In patients with signs and symptoms of worsening heart failure, such as edema, weight gain or dyspnea, the dosage of diuretic therapy should be increased.

If evidence of worsening heart failure persists, the dosage of carvedilol should be decreased. In patients with bradycardia or first-degree atrioventricular block, carvedilol should be titrated to maintain a heart rate greater than 55 beats per minute. Finally, patients should be advised not to stop taking carvedilol abruptly or without a physician's advice.

When carvedilol therapy must be discontinued, the drug should be tapered slowly over seven to 14 days. Carvedilol is supplied in tablet form and is available in four dosage strengths: 3. Already a member or subscriber? Log in. Interested in AAFP membership? Learn more. He received a medical degree from the University of Pennsylvania School of Medicine, Philadelphia, and completed a residency in family practice at York Pa.

Address correspondence to Bruce T. Vanderhoff, M. Grant Ave. Reprints are not available from the authors. Eichhorn EJ. Do beta-blockers have a role in patients with congestive heart failure? Cardiol Clin. Effects of carvedilol, a vasodilator-beta-blocker, in patients with congestive heart failure due to ischemic heart disease. Sharpe N. Beta-blockers in heart failure. Future directions. Eur Heart J.

Rationale for treatment of patients with chronic heart failure with adrenergic blockade. Cohn JN. The management of chronic heart failure. N Engl J Med. Practical guidelines for initiation of beta-adrenergic blockade in patients with chronic heart failure [Editorial].

Am J Cardiol. Packer M. Beta-blockade in the management of chronic heart failure. There has also been an unresolved debate as to whether bucindolol is associated with intrinsic sympathomimetic activity Andreka et al ; Maack et al Should this be the case it might explain the failure of bucindolol similarly to the xamoterol trial described above. Impressive results have been obtained with carvedilol.

In this study patients with CHF were randomized to receive either carvedilol or placebo Packer et al The trial was designed to evaluate the safety of treatment with carvedilol and mortality was observed as a secondary f inding. As for the primary end point, a significant reduction in the risk of hospitalization was found and worsening of heart failure was reduced in the group treated with carvedilol. The problem with interpreting the results of this study was that it was stopped early and was a meta-analysis of a group of studies designed to demonstrate symptomatic relief of carvedilol.

These problems became secondary with the study of carvedilol in patients with severe heart failure. The effect, previously seen in the group with mild or moderate heart failure, was thereby reproduced in patients with severe heart failure. The initial primary endpoint of this study was all-cause mortality. During the trial the steering committee noted that all-cause mortality was lower than expected, and they changed the primary endpoint to the combination of all-cause mortality and all-cause hospitalization.

Eventually the original endpoint came out positive and the new endpoint was neutral. To regulatory authorities, CAPRICORN was therefore a negative study, to a general scientific interpretation there are no specific rules and many consider the trial positive. As a net result it is widely accepted that beta-blocker therapy has substantial benefit to patients with heart failure, with, and without myocardial infarction. One of many important questions that remain is whether different beta-blockers have different value.

The first developed beta-blockers, the so-called first generation beta-blockers, was a non-specific beta-blocker that blocks both beta1- and beta2-adrenoceptors. Propranolol, the traditionally used first-generation beta-blocker, is not recommended for use in heart failure patients: it has not been tested. Metoprolol and bisoprolol belongs to the group of second generation beta-blockers with a specific beta1-blockade.

The third-generation beta-blockers include carvedilol and bucindolol and have a non-selective beta-blocking effect on both beta1- as well as beta2adrenoceptors. Carvedilol further has an alpha-blocking effect which results in a vasodilating property. Bucindolol also has a vasodilating property. The reason for the vasodilating property of bucindolol has not clearly been demonstrated, but it may be because of an intrinsic sympatomimetic effect.

In addition to the adrenergic blocking properties carvedilol it has an antioxidant effect and suppresses endothelin biosynthesis Yue et al ; Ohlstein et al ; Lysko et al ; Arumanayagam et al Metoprolol, a second-generation beta-blocker was compared with the third-generation beta-blocker carvedilol Poole-Wilson et al Both beta-blockers have been proven beneficial for use in a group of patients with heart failure Packer et al , The aim of the trial from the outset was to study whether the extra effects of carvedilol mattered clinically and therefore the trial was designed to ensure as close as possible beta-1 blocking effect in the two study groups.

Both beta-blockers were well tolerated, and no differences were seen in terms of side-effects or withdrawals Torp-Pedersen, Poole-Wilson, et al A significant reduction in mortality was observed in favour of the group treated with carvedilol, with an absolute reduction in mortality of 5.

Similarly to the reduction in mortality, a reduction in mortality due to cardiovascular reasons, stroke, sudden death, and death caused by circulatory failure was seen in the group treated with carvedilol.

No differences were seen between the two groups as it comes to worsening in heart failure, hospitalizations, and cause-specific hospitalizations Torp-Pedersen, Poole-Wilson, et al Mean duration of follow-up was 58 months, but the benefit, in concern of reduced mortality among the patients treated with carvedilol, appeared already at 6 months of observation.

Lancet, — Criticism has been focused on the choice of formulation of metoprolol. The question is then whether this formulation can improve mortality and is worthy of comparison with carvedilol. Need for transplantation was used as an expression for deterioration of heart failure. No reduction in all-cause mortality was observed, possibly due to a very low number of deaths in the trial. But when follow up was extended a beneficial effect on mortality was indeed observed with IR metroprolol MDC The basic question is, whether the apparent superior effect on mortality seen with carvedilol compared with IR metoprolol, has any relevance to a higher dose and more sustained blockade that is obtained with mg of CR metoprolol as was used in MERIT-HF.

To assess the degree of beta1-blockade the most accepted method is to study exercise-induced increase in heart rate HR. In the COMET trial no evaluation of the relative beta1-blockade of the two beta-blockers used was performed. The only information collected was the resting HR. A significant albeit small difference in the reduction of HR obtained was observed in the carvedilol arm, no difference in HR was seen beyond the f irst year of observation Figure 2 Packer As carvedilol exert different adrenoceptor blocking properties besides its antioxidative effect, it is of interest to know which mechanism gives carvedilol its favorable effect in superiority to metoprolol on mortality.

The alpha-blocking properties have been tested. Doxazosin, a selective alpha1-blocker, versus placebo was tested in 73 patients with CHF DiBianco et al Both investigators and patients assessment of symptomatic change was improved after treatment with doxazosin.

When doxazosin was added to the beta1-blocker metoprolol in patients with heart failure, no improvement in hemodynamic measurements were seen, when compared with patients only treated with metoprolol Kukin et al Even though carvedilol does not have the same pharmacokinetic properties as the combination of doxazosin and metoprolol, this study indicates that the beneficial effect seen with carvedilol is less likely to be caused solely by the alpha1-blocking properties of carvedilol.