HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Respond to This Article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Albert, N. M. Search for Related Content PubMed PubMed Citation Articles by Albert, N. M.

Switching to Once-Daily Evidence-Based β-Blockers in Patients With Systolic Heart Failure or Left Ventricular Dysfunction After Myocardial Infarction

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.

Financial Disclosures
The author is a member of the speaker’s bureau and a consultant for Glaxo Smith Kline (Philadelphia, Pennsylvania).

Corresponding author: Nancy M. Albert, RN, PhD, Director, Nursing Research and Innovation, Division of Nursing, 9500 Euclid Ave, Mail Code P32, Cleveland, OH 44195 (e-mail: albertn{at}ccf.org).

Perhaps the easiest way to improve clinical and health outcomes is to improve adherence to the drug treatment plan by simplifying the medication regimen⁴ (Figure 1). Among patients with heart failure and other cardiovascular conditions, such as hypertension, changing regimens from doses taken 2 or 3 times a day to a dose taken once a day increased adherence.^5–8 In a large meta-analysis,⁴ increased treatment adherence improved health outcomes, including survival, readmission rates, blood pressure, cholesterol level, and hemoglobin A_1c level. Fewer pills per day may be particularly beneficial for patients after myocardial infarction or for patients with heart failure.⁹

View larger version (39K): [in this window] [in a new window]   Figure 1 Model of the benefits of once-daily versus multiday dosing of medications.

In this article, I discuss the practical considerations of the use of evidence-based β-blockers. Specifically, I propose changing from twice-daily to once-daily β-blockers and changing from commonly used non–evidence-based agents to evidence-based, once-daily β-blockers in patients with heart failure and patients with left ventricular systolic dysfunction (LVSD) after myocardial infarction. In patients with chronic systolic heart failure and LVSD and heart failure after myocardial infarction, β-blockade is considered a key pharmaceutical therapy.^17,18 Simplifying the β-blocker regimen with once-daily dosing offers an opportunity to improve patients’ outcomes by boosting the probability of adherence to treatment. Availability of once-daily formulations of evidence-based β-blockers should prompt nurses to consider a new treatment model to help overcome the barrier to adherence created by high dosing frequency.

	Literature Review

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
Simplifying a patient’s medical regimen by reducing dosing frequency to once a day is likely to be associated with improved adherence to therapy, greater satisfaction among patients, and possibly more favorable outcomes. In a recent study,¹⁹ researchers compared patients’ compliance (measured electronically) and treatment effectiveness in patients with stable angina pectoris treated with oral nitrates administered once daily versus twice daily. Patients receiving once-daily therapy had significantly greater overall medication adherence than did patients receiving twice-daily therapy (88.9% vs 73.8%; P<.001), a higher percentage of days with the correct number of doses taken (85.5% vs 59.5%; P<.001), and a greater reduction in mean number of episodes of weekly chest pain (94% less vs 30% less; P<.001).¹⁹

Many researchers^20–27 have studied the effects of daily doses on drug adherence in both observational studies and randomized clinical trials. Simply put, once-daily agents were taken more regularly than were twice-daily agents,^20–27 supporting better adherence to drug regimens; however, whether the use of once-daily β-blockers improves adherence has not yet been assessed in a clinical trial.

Specific to β-blocker therapy, improved adherence has been associated with improved outcomes in 2 studies.^28,29 In patients with heart failure, lower adherence to metoprolol tartrate was associated with a higher rate of emergency room visits (P<.001) and hospital admissions (P<.001).²⁸ After surviving a myocardial infarction, patients in the Beta Blocker Heart Attack Trial who took 75% or less of prescribed β-blockers were 2.6 times more likely to die in the first year of follow-up than were patients who were adherent to therapy.²⁹

	β-Blockers in Heart Failure

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
The American College of Cardiology/American Heart Association management guidelines include recommendations that long-term therapy with β-blockers be started and continued indefinitely in all survivors of acute myocardial infarction who do not have absolute contraindications¹⁷ and in patients with mild to severe heart failure.¹⁸ β-Blockers significantly reduced mortality in patients with heart failure and acute myocardial infarction in several large-scale randomized clinical trials^17,30–35 and in a national registry of patients hospitalized for acute decompensated heart failure.³⁶

Only carvedilol and metoprolol succinate are approved in the United States for the treatment of heart failure (Table 1).¹⁸ Carvedilol (both formulations, see following) is the only β-blocker approved by the US Food and Drug Administration for patients with LVSD after myocardial infarction; approval was based on mortality benefits of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRI-CORN) trial.³⁵ Carvedilol is also the only β-blocker approved for use in patients with severe advanced, chronic heart failure.³⁷

	Switching From Carvedilol to Carvedilol CR (Carvedilol Phosphate Extended-Release)

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

Bioequivalence
The 2 formulations of carvedilol (twice-daily dosing with the original formulation and once-daily dosing with carvedilol CR) have equivalent steady-state pharmacokinetic characteristics and pharmacodynamic properties.^40,41 The pharmacokinetic profile of the 2 formulations was compared in patients with mild to severe heart failure and in patients with asymptomatic LVSD after myocardial infarction.⁴² The mean steady-state concentration-time profile of the β-blocking enantiomer, S(–)-carvedilol, was equivalent between the 2 formulations in a crossover pharmacokinetic study of 188 patients with mild to severe heart failure or asymptomatic LVSD after myocardial infarction, reflecting no discernible difference between carvedilol and carvedilol CR.⁴² Additionally, medication adherence was better in the carvedilol CR group (93% vs 85%); however, this open-label clinical trial did not have sufficient power to allow statistical evaluation of differences in adherence between the groups.⁴²

Tolerability
Less-frequent dosing regimens combined with a favorable tolerability profile result in better medication-taking behavior.^20,43,44 Surveys^45–47 have repeatedly indicated that the occurrence of adverse effects is an important predictor of nonadherence by patients. The original twice-daily carvedilol formulation had a favorable tolerability profile; common adverse effects reported by patients with heart failure that were deemed likely to be related to the drug were dizziness, fatigue, hypotension, and bradycardia.⁴⁸

Data from the US Carvedilol Heart Failure trial³³ and the Carvedilol Prospective Randomized Cumulative Survival study³⁴ revealed that fewer patients receiving carvedilol than patients receiving placebo discontinued therapy because of adverse events. In elderly patients with heart failure who were receiving carvedilol, overall tolerability at 6 months was between 77% and 84%.⁴⁹ In a study of carvedilol CR in patients with LVSD, the once-daily formulation had similar tolerability to the twice-daily carvedilol formulation,⁴⁰ indicating equivalence in safety when patients are switched from twice-daily carvedilol to once-daily carvedilol CR.

Switching patients from twice-daily carvedilol to once-daily carvedilol CR is straightforward; the once-daily doses of 10, 20, 40, and 80 mg of carvedilol CR are equivalent to the 4 twice-daily dose levels of carvedilol, respectively (Table 2).⁴⁰ Patients currently taking twice-daily carvedilol should start the equivalent dose of carvedilol CR the following morning after their last evening dose of carvedilol.

	Clinical Rationale for Choosing a Specific Evidence-Based β-Blocker

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

In a substudy⁵⁴ of adverse events from the Carvedilol or Metoprolol European Trial, more events related to new onset of diabetes (diabetic coma, peripheral gangrene [diabetic foot], decreased glucose tolerance, hyperglycemia) occurred in patients with heart failure who were taking metoprolol tartrate than in patients taking carvedilol (13.0% vs 10.6%; hazard ratio = 0.78; 95% confidence interval [CI], 0.61–0.99; P=.04).⁵⁴ Additionally, patients with LVSD after myocardial infarction should be preferentially switched to carvedilol CR, because other β-blockers are not indicated in such patients.

Some clinical situations may warrant choosing metoprolol succinate over carvedilol. Patients with reactive airway disease could have an exacerbation of their underlying disease by the β₂-receptor–blocking property of carvedilol.⁴⁸ Because of its relative β₁-selectivity, metoprolol succinate can be used with caution in patients with bronchospastic disease. However, because β₁-selectivity is not absolute, a β₂-stimulating agent should be administered concomitantly and the lowest possible dose of metoprolol succinate should be used.⁵⁵

Dosing requirement is an important factor in medication nonadherence and may adversely affect elderly patients. Reductions in mortality have been observed for patients with heart failure who were consistently treated with low doses of carvedilol (6.25 twice daily),³⁰ yet a similar mortality benefit was observed only in patients who had their doses of metoprolol succinate adjusted to a higher equivalent.³¹ Thus, when the dose of metoprolol succinate cannot be titrated up to the level of target doses used in large, randomized, controlled trials, switching from metoprolol succinate to carvedilol may be beneficial, especially in elderly patients.

	Clinical Rationale for Switching Patients With LVSD From Non–Evidence-Based β-Blockers to Evidence-Based β-Blockers

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
Switching from a non–evidence-based β-blocker to an evidence-based agent was safe in the Carvedilol or Metoprolol European Trial.⁵⁶ The recommended starting dose was half the equivalent of the last study medication dose; for example, if the current metoprolol dose was 100 mg/day (50 mg twice daily), then the starting dose of carvedilol would be the equivalent of 50 mg/day metoprolol (6.25 mg twice daily). Among patients taking carvedilol who were switched to metoprolol tartrate, 9.4% experienced a serious adverse event (discontinuation of therapy due to dizziness, bradycardia, headache, or presyncope), and 4.7% experienced worsening heart failure (worsening New York Heart Association functional class).

In patients switched from metoprolol tartrate to carvedilol, 3.1% experienced a serious adverse event, and 1.5% experienced worsening heart failure.⁵⁶ In a single-center study⁵⁷ of 30 patients with baseline mean left ventricular ejection fractions of 29%, compared with patients maintained on metoprolol therapy, patients who switched treatment from metoprolol to carvedilol had an improvement in left ventricular ejection fraction (+7%, standard error of the mean [SEM] ±3% vs –1%, SEM ±2%; P=.04). In a comparison⁵⁸ of the effects of metoprolol tartrate and carvedilol in 150 patients, patients receiving carvedilol had a significantly greater improvement in ejection fraction after 12 months of treatment (carvedilol: from 20.4% [SEM ±7.6%] to 31.2% [SEM ±11.9%] vs metoprolol: 21.6% [SEM ±7.2%] to 28.8.2% [SEM ±11.3%], P=.03).

Ultimately, nurses with prescriptive privileges should consider switching patients with heart failure from a non–evidenced-based β-blocker (eg, atenolol or metoprolol tartrate) to an evidence-based agent (carvedilol, carvedilol CR, metoprolol succinate, or bisoprolol). Cardiac nurses without prescriptive privileges are key team members in ensuring implementation of processes that optimize ordering and administration of drug therapy and should ensure that patients are on an evidence-based β-blocker therapy before discharge from the hospital.

	Practical Aspects of Switching Strategies for Switching

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
Table 3 shows a strategy for switching patients with heart failure from 2 common non–evidence-based β-blockers to carvedilol CR, metoprolol succinate, or bisoprolol, once-daily agents.^56,59–61 The strategy is based on suggestions from previous publications as well as the dose equivalency observed in the carvedilol and carvedilol CR profiles.^40–42 Figure 2 shows a strategy for switching from non–evidence-based β-blockers to carvedilol CR in patients with LVSD after myocardial infarction.⁶²

View larger version (35K): [in this window] [in a new window]   Figure 2 Strategy for switching treatment from non–evidence-based β-blockers to carvedilol phosphate extended-release (carvedilol CR) in patients with left ventricular systolic dysfunction after myocardial infarction.62

Considerations in Patients With Heart
Failure Patients with heart failure who are currently being treated with a non–evidence-based agent such as metoprolol tartrate or atenolol should be switched to metoprolol succinate, carvedilol CR, or bisoprolol. When patients with hypertension are treated with β-blockers such as atenolol or metoprolol tartrate and then LVSD or heart failure develops, the patients’ treatment should be switched to a β-blocker that has proved effective in reducing poor outcomes in heart failure (Table 3). When β-blockers are being switched, especially to a nonselective agent with -blocking effects, patients should be started at a low dose to ensure tolerance. Once the β-blocker has been tolerated for 2 weeks, the dose can be titrated up to the maximal dose as tolerated over time by doubling the dose stepwise every 2 weeks.⁶³ Although a change from one β-blocker to another is generally safe and well tolerated, monitoring for adverse effects should be routine whenever medications are switched.

The switch to a once-daily evidence-based β-blocker can be done 12 hours after the last dose of a twice-daily agent by beginning the first dose of the new agent the next morning after the last dose of the old agent was taken the previous evening. Likewise, treatment with a once-daily evidence-based β-blocker can be started 24 hours after a once-daily non–evidence-based agent is discontinued. In patients at high risk for precipitating or worsening ischemia, an option rather than direct switching is maintaining full β₁-blockade and gradually increasing β₁-mediated vasodilatation in a stepwise fashion by overlapping decreasing doses of metoprolol tartrate or atenolol with increasing doses of carvedilol every 2 weeks. It is crucial not to add agents with vasodilatory properties, such as calcium antagonists, nitrates, or other antihypertensives, directly before carvedilol. The details on how to switch β-blockers with this overlapping protocol were developed by W. T. Abraham.⁵⁹

If switching to another β-blocker is being considered because of a lack of clinical response, the patient’s condition should first be stabilized by modulating his or her diuretic or angiotensin-converting enzyme inhibitor. Switching β-blockers as a form of rescue therapy while a patient’s clinical condition is deteriorating is not recommended. For patients experiencing severe decompensation of heart failure, destabilization of clinical condition, marked hypotension, or continuing requirements for intravenous inotropes or diuretics, switching β-blockers is not recommended.⁵⁹ On the other hand, a switch in β-blocker might be considered in patients whose disease is either not improving or is progressing despite treatment with another β-blocking agent (Table 4). Before a switch in β-blocker therapy, all other medication dosing should be stable (steady state), and patients should be free of volume overload.

Switching from non–evidence-based oral agents to carvedilol CR is shown in Figure 2. In patients with LVSD after myocardial infarction and recent symptomatic heart failure, carvedilol CR may be started at 10 mg rather than 20 mg and titrated to the highest dose tolerated. In hospitalized patients with LVSD after myocardial infarction, twice-daily carvedilol may be selected because of its shorter half-life and caregiver familiarity. Nurses can be the gatekeepers in ensuring that patients are switched to a once-daily dose formulation before discharge to increase the probability of better adherence to the medication regimen.

Monitoring During the Switch
During any switch of β-blocking agents, nurses should closely monitor each patient’s tolerance and medication adherence. Careful objective and subjective assessment may be warranted. Additionally, before a patient is discharged from the hospital, nurses should provide clear instructions about signs and symptoms of worsening heart failure and should assess the patient’s understanding of what he or she has been taught. These precautions may increase recognition of an adverse event before the event becomes serious or severe.

	Importance of Nurse-Based Management

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
Critical care, cardiac, and advanced practice nurses are charged with the day-to-day care of hospitalized patients with heart failure and LVSD after myocardial infarction. Through the use of therapy recommended in guidelines and thoughtful prescribing patterns, nurses can improve patients’ clinical outcomes (fewer hospitalizations and improved quality of life); however, results of research on patients’ overall well-being in relation to once-daily vs twice-daily dosing of drug therapies are not available. In the Carvedilol or Metoprolol European Trial, assessment of well-being was associated with New York Heart Association functional class but not with the patient’s age or sex or with the β-blocker used.⁶⁹ If once-daily β-blocker therapy creates a large enough change in total dose regularly received, functional class possibly could improve to a greater degree, improving subjective well-being.

A nurse’s responsibilities include educating patients and caregivers, initiating treatment with and titrating doses of therapeutic drugs, identifying and following a nursing plan of care (in addition to physicians’ orders), supervising adherence to drug and nonpharmacological care strategies, and advocating for patients. If agents known to decrease mortality and improve functional status are used, patients are more likely to have fewer emergency room visits and unplanned hospitalizations, greater satisfaction with well-being, and improved quality of life.

The success of patients’ treatment is affected by expert multidisciplinary care and also by the level of involvement of nurse caregivers, who are often the mediators of evidence-based practice and are responsible for ongoing collaboration and communication with other members of the healthcare team. For example, physicians may be reluctant to initiate a switch in β-blocker treatment because switching requires closer monitoring and upward titration of the dose. Or a physician may tell a patient why the patient is being treated with a β-blocker but not explain the expectations related to starting treatment with that drug. Thus, if patients become more fatigued or dizziness develops, they may think the drug is not for them and stop taking it. A gap clearly exists between the evidence that supports treatments used in heart failure and patients who have had a myocardial infarction and actual practice in day-to-day patient care.^70,71 Because multiple registries have shown that the prescription of lifesaving therapies is not yet optimal, and studies have shown that patients’ adherence to therapies is poor, innovative practice improvement programs, clinical leaders, and system tools are needed to close the gap. As part of a multidisciplinary team of healthcare providers, nurses can use clinical pathways/protocols, interdisciplinary rounds, and case study discussions to facilitate processes that advance planning of patients’ care and promote effective care delivery.⁷²

In a randomized controlled clinical trial⁷³ of 169 patients with heart failure, ejection fraction of 45% or less, and no contraindications to use of β-blockers, primary providers were randomly stratified to 1 of 3 interventions: (1) physician education (including substantial education on the use of β-blockers in heart failure, including grand rounds presentations, conferences, and distribution of letters and e-mails with guidelines for β-blocker initiation and upward titration of the dose); (2) provider and patient notification (physicians were alerted via computer messages when they accessed a patient’s electronic record for the first 2 visits after randomization, and patients were alerted via letters informing them that they might be candidates for β-blocker therapy and that they should discuss this treatment with their primary provider); and (3) use of a nurse facilitator (a nurse practitioner supervised by 2 cardiologists assumed responsibility for initiating treatment with β-blockers, titrating the dose, and stabilizing a patient’s clinical condition in appropriate patients with heart failure).

The primary outcome, the proportion of patients who started treatment with β-blockers or had the dose titrated upward and were maintained on β-blockers, was achieved in 67% (36 of 54) of patients in the nurse facilitator group compared with 16% (10 of 64) of patients in the provider-patient notification group and 27% (14 of 51) of patients in the physician education group (P<.001 for the comparisons between the nurse facilitator group and both other groups). The proportion of patients receiving target doses of β-blockers at the end of the study (median follow-up 12 months) was also higher (P < .001) in the nurse facilitator group (43%) than in the physician education group (10%) and the provider/patient notification group (2%). The frequency of adverse events did not differ among groups.⁷³

Cardiac nurses are well placed to facilitate improvements in care and advocate for changes in therapy when warranted. As evidenced in the study⁷³ just described, advanced practice nurses with prescription privileges can successfully implement treatment with an evidence-based β-blocker in indicated patients. The switching algorithms provided here can be instrumental in helping nurses improve care.

	Conclusion

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 
Adherence to pharmacological therapies in cardiovascular disease is poor, leading to worsening disease severity and rehospitalization. Barriers to medication adherence are numerous, including complex medication regimens, adverse effects, and poor education of patients. Nurses can increase the use of lifesaving therapies by implementing treatment at discharge and using once-daily agents that will result in easier regimens that, in turn, may improve patients’ adherence and lead to better outcomes. After assessing a patient’s current medical and device therapies and his or her ability to adhere to medication, nurses may find that switching β-blockers is warranted. Nurse-led management programs have shown that nurses can markedly influence patients’ outcomes by educating patients about medication regimens.

The availability of once-daily formulations of β-blocker therapies with favorable tolerability may enhance adherence to therapy with evidence-based agents. Three once-daily β-blocker therapies are acceptable for treatment of patients with heart failure: carvedilol CR, metoprolol succinate, and bisoprolol. Carvedilol CR is also indicated for the treatment of patients with LVSD after myocardial infarction. Once-daily formulations can promote use of evidence-based β-blocker therapy that assist nurses in providing quality care and ensuring patients’ safety.

	References

Top Literature Review β-Blockers in Heart Failure Switching From Carvedilol to... Clinical Rationale for Choosing... Clinical Rationale for Switching... Practical Aspects of Switching... Importance of Nurse-Based... Conclusion References

 

1. Balkrishnan R. Predictors of medication adherence in the elderly. Clin Ther. 1998; 20(4):764–771.[Medline]
2. Masoudi FA, Baillie CA, Wang Y, et al. The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998–2001. Arch Intern Med. 2005;165(18):2069–2076.[Abstract/Free Full Text]
3. Spencer FA, Meyer TE, Gore JM, Goldberg RJ. Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure. The National Registry of Myocardial Infarction. Circulation. 2002;105(22):2605–2610.[Abstract/Free Full Text]
4. DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002;40(9):794–811.[Medline]
5. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–1310.[Medline]
6. Schroeder K, Fahey T, Ebrahim S. How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials. Arch Intern Med. 2004;164(7):722–732.[Abstract/Free Full Text]
7. Iskedjian M, Einarson TR, MacKeigan LD, et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin Ther. 2002;24:302–316.[Medline]
8. Hope CJ, Wu J, Tu W, Young J, Murray MD. Association of medication adherence, knowledge, and skills with emergency department visits by adults 50 years or older with congestive heart failure. Am J Health Syst Pharm. 2004;61(19):2043–2049.[Abstract/Free Full Text]
9. Vinson JM, Rich MW, Sperry JC, Shah AS, McNamara T. Early readmission of elderly patients with congestive heart failure. J Am Geriatr Soc. 1990;38(12):1290–1295.[Medline]
10. Leventhal MJ, Riegel B, Carlson B, De Geest S. Negotiating compliance in heart failure: remaining issues and questions. Eur J Cardiovasc Nurs. 2005;4(4):298–307.[Medline]
11. Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med. 1995;333(18): 1190–1195.[Abstract/Free Full Text]
12. Aubert RE, Herman WH, Waters J, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization: a randomized, controlled trial. Ann Intern Med. 1998;129(8):605–612.[Abstract/Free Full Text]
13. Allen JK, Blumenthal RS, Margolis S, Young DR, Miller ER III, Kelly K. Nurse case management of hypercholesterolemia in patients with coronary heart disease: results of a randomized clinical trial. Am Heart J. 2002; 144(4):678–686.[Medline]
14. Becker DM, Raqueno JV, Yook RM, et al. Nurse-mediated cholesterol management compared with enhanced primary care in siblings of individuals with premature coronary disease. Arch Intern Med. 1998;158(14): 1533–1539.[Abstract/Free Full Text]
15. Logan AG, Milne BJ, Flanagan PT, Haynes RB. Clinical effectiveness and cost-effectiveness of monitoring blood pressure of hypertensive employees at work. Hypertension. 1983;5(6):828–836.[Abstract/Free Full Text]
16. Artinian NT, Washington OG, Templin TN. Effects of home telemonitoring and community-based monitoring on blood pressure control in urban African Americans: a pilot study. Heart Lung. 2001;30(3):191–199.[Medline]
17. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation. 2004;110(9):e82–e293.[Free Full Text]
18. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). American College of Cardiology Web site. http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf. Accessed October 2, 2007.
19. Kardas P; COMPASS Investigators. Comparison of once daily versus twice daily oral nitrates in stable angina pectoris. Am J Cardiol. 2004;94(2):213–216.[Medline]
20. Bloom BS. Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther. 1998;20(4):671–681.[Medline]
21. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150(9):1881–1884.[Abstract/Free Full Text]
22. Leenen FH, Wilson TW, Bolli P, et al. Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Can J Cardiol. 1997; 13(10):914–920.[Medline]
23. Girvin B, McDermott BJ, Johnston GD. A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance. J Hypertens. 1999;17(11):1627–1631.[Medline]
24. Hilleman DE, Mohiuddin SM, Lucas BD Jr, Shinn B, Elsasser GN. Conversion from sustained-release to immediate-release calcium entry blockers: outcome in patients with mild-to-moderate hypertension. Clin Ther. 1993;15(6):1002–1010.[Medline]
25. Sica DA. Fixed-dose combination antihypertensive drugs: do they have a role in rational therapy? Drugs. 1994;48(1):16–24.[Medline]
26. Erne P, Saxenhofer H, Waeber B, Heynen G. Time of drug intake in hypertension and angina pectoris: a controlled monitoring study [in German]. Schweiz Rundsch Med Prax. 1994;83(39):1079–1083.[Medline]
27. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–497.[Free Full Text]
28. Tu W, Morris AB, Li J, et al. Association between adherence measurements of metoprolol and health care utilization in older patients with heart failure. Clin Pharmacol Ther. 2005;77(3):189–201.[Medline]
29. Horwitz RI, Viscoli CM, Berkman L, et al. Treatment adherence and risk of death after a myocardial infarction. Lancet. 1990; 336(8714):542–545.[Medline]
30. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation. 1996;94(11):2807–2816.[Abstract/Free Full Text]
31. MERIT-HF Investigators. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001–2007.[Medline]
32. Packer M, Colucci WS, Sackner-Bernstein JD, et al. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise. Circulation. 1996;94(11):2793–2799.[Abstract/Free Full Text]
33. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349–1355.[Abstract/Free Full Text]
34. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Circulation. 2002;106(17): 2194–2199.[Abstract/Free Full Text]
35. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001; 357(9266):1385–1390.[Medline]
36. Fonarow GC, Abraham WT, Albert NM, et al. Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF). Am Heart J. 2007;153(1):82–89.[Medline]
37. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22): 1651–1658.[Abstract/Free Full Text]
38. Fonarow GC. Profile of carvedilol controlled-release: a new once-daily formulation of carvedilol. Expert Opin Pharmacother. 2006; 7(18):2533–2546.[Medline]
39. Hauptman PJ, Pressler SJ, Sackner-Bernstein J, Ordronneau P, Udelson JE, for the CASPER Investigators. Rationale and design of CASPER: compliance and quality of life study comparing once-daily carvedilol CR and twice-daily carvedilol IR in patients with heart failure. Am J Cardiol. 2006; 98(7A):60L–66L.[Medline]
40. Tenero DM, Henderson LS, Baidoo CA, et al. Pharmacokinetic properties of a new controlled-release formulation of carvedilol. Am J Cardiol. 2006;98(7A):5L–16L.[Medline]
41. Tenero DM, Henderson LS, Campanile AM, Baidoo CA, Boyle D. Development of a pharmacokinetic/pharmacodynamic model for carvedilol to predict β₁-blockade in patients with congestive heart failure. Am J Cardiol. 2006;98(7A):27L–31L.[Medline]
42. Packer M, Lukas MA, Tenero DM, Baidoo CA, Greenberg BH; 369 Study Group. Pharmacokinetic profile of controlled-release carvedilol in patients with left ventricular dysfunction associated with chronic heart failure or after myocardial infarction. Am J Cardiol. 2006;98(7A):39L–45L.[Medline]
43. Hasford J, Mimran A, Simons WR. A population-based European cohort study of persistence in newly diagnosed hypertensive patients. J Hum Hypertens. 2002; 16(8):569–575.[Medline]
44. Burnier M, Hess B, Greminger P, Waeber B. Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey. BMC Cardiovasc Disord. 2005;5(1):13.[Medline]
45. Richardson MA, Simons-Morton B, Annegers JF. Effect of perceived barriers on compliance with antihypertensive medication. Health Educ Q. 1993;20(4):489–503.[Medline]
46. Fincke BG, Miller DR, Spiro A III. The interaction of patient perception of over-medication with drug compliance and side effects. J Gen Intern Med. 1998;13(3):182–185.[Medline]
47. Nelson EC, Stason WB, Neutra RR, Solomon HS. Identification of the noncompliant hypertensive patient. Prev Med. 1980;9(4): 504–517.[Medline]
48. Coreg (carvedilol) tablets [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2005.
49. Krum H, Hill J, Fruhwald F, et al. Tolerability of beta-blockers in elderly patients with chronic heart failure: the COLA II study. Eur J Heart Fail. 2006;8(3):302–307.[Medline]
50. Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension: a randomized, controlled trial. Ann Intern Med. 1997;126(12):955–959.[Abstract/Free Full Text]
51. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292(18):2227–2236.[Abstract/Free Full Text]
52. Haenni A, Lithell H. Treatment with a beta-blocker with beta₂-agonism improves glucose and lipid metabolism in essential hypertension. Metabolism. 1994;43(4):455–461.[Medline]
53. Basat O, Ucak S, Seber S, Oztekin E, Altuntas Y. After myocardial infarction carvedilol improves insulin resistance compared to metoprolol. Clin Res Cardiol. 2006;95(2): 99–104.[Medline]
54. Torp-Pedersen C, Metra M, Charlesworth A, et al. Effects of metoprolol and carvedilol on preexisting and new onset diabetes in patients with chronic heart failure: data from the Carvedilol or Metoprolol European Trial (COMET). Heart. 2007;93(8):968–973.[Abstract/Free Full Text]
55. Toprol XL (metoprolol succinate) extended-release tablets [prescribing information]. Wilmington, DE: AstraZeneca; 2005.
56. Di Lenarda A, Remme WJ, Charlesworth A, et al. Exchange of beta-blockers in heart failure patients: experiences from the post-study phase of COMET (the Carvedilol or Metoprolol European Trial). Eur J Heart Fail. 2005;7(4):640–649.[Medline]
57. Di Lenarda A, Sabbadini G, Salvatore L, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group. J Am Coll Cardiol. 1999;33(7):1926–1934.[Abstract/Free Full Text]
58. Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei Cas L. Differential effects of β-blockers in patients with heart failure: a prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol. Circulation. 2000;102(5):546–551.[Abstract/Free Full Text]
59. Abraham WT. Switching between beta blockers in heart failure patients: rationale and practical considerations. Congest Heart Fail. 2003;9(5):271–278.[Medline]
60. Blomqvist I, Westergren G, Sandberg A, Jonsson UE, Lundborg P. Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: a comparison with atenolol. Eur J Clin Pharmacol. 1988;33(suppl):S19–S24.[Medline]
61. Abraham WT. Switching to evidence-based once-daily β-blockers for improved adherence to medication across the continuum of post-myocardial infarction left ventricular dysfunction and heart failure. Congestive Heart Fail. In press.
62. Fonarow GC. Practical considerations of beta-blockade in the management of the post-myocardial infarction patient. Am Heart J. 2005;149(6):984–993.[Medline]
63. Coreg CR (carvedilol phosphate) extended-release capsules [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2007.
64. Monocor (bisoprolol fumarate) tablets [prescribing information]. Bridgewater, NJ: Biovail Pharmaceuticals; 2004.
65. ISIS-1 Collaborative Group. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction: ISIS-1. First International Study of Infarct Survival Collaborative Group. Lancet. 1986;2(8498):57–66.[Medline]
66. Hjalmarson A, Elmfeldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. Lancet. 1981;2(8251):823–827.[Medline]
67. Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 1981; 304(14):801–807.[Abstract]
68. MIAMI Trial Research Group. Metoprolol in acute myocardial infarction: mortality. The MIAMI Trial Research Group. Am J Cardiol. 1985;56(14):15G–22G.[Medline]
69. Cleland JG, Charlesworth A, Lubsen J, et al. A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure. J Am Coll Cardiol. 2006;47(8):1603–1611.[Abstract/Free Full Text]
70. Fonarow GC, Abraham WT, Albert NM, et al; OPTIMIZE-HF Investigators and Hospitals. Association between performance measures and clinical outcomes for patients hospitalized with heart failure. JAMA. 2007;297(1):61–70.[Abstract/Free Full Text]
71. Fonarow GC, Heywood JT, Heidenreich PA, Lopatin M, Yancy CW; ADHERE Scientific Advisory Committee and Investigators. Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2007;153(6):1021–1028.[Medline]
72. Albert NM. Evidence-based nursing care for patients with heart failure. AACN Adv Crit Care. 2006;17(2):170–183.[Medline]
73. Ansari M, Shlipak MG, Heindenreich PA, et al. Improving guideline adherence: a randomized trial evaluating strategies to increase β-blocker use in heart failure. Circulation. 2003;107(22):2799–2804.[Abstract/Free Full Text]

This article has been cited by other articles:

				N. M. Albert Improving Medication Adherence in Chronic Cardiovascular Disease Crit. Care Nurse, October 1, 2008; 28(5): 54 - 64. [Full Text] [PDF]

This Article Full Text (PDF) Respond to This Article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Albert, N. M. Search for Related Content PubMed PubMed Citation Articles by Albert, N. M.