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Medication Safety Issues
Sound-alike/look-alike issues:
Zebeta® may be confused with DiaBeta®, Zetia®
Pronunciation
(bis OH proe lol)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension, alone or in combination with other agents
Use: Unlabeled/Investigational
Chronic stable angina, supraventricular arrhythmias, PVCs, heart failure (HF)
Pregnancy Risk Factor
C (manufacturer); D (2nd and 3rd trimesters - expert analysis)
Pregnancy Considerations
No data available on whether bisoprolol crosses the placenta. Beta-blockers have been associated with persistent bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
Lactation
Enters breast milk/use caution
Contraindications
Cardiogenic shock; overt cardiac failure; marked sinus bradycardia; heart block greater than first-degree (except in patients with a functioning artificial pacemaker)
Warnings/Precautions
Concerns related to adverse events:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; for patients with bronchospastic disease who do not respond to or cannot tolerate other therapies, initial low doses of beta1-selective bisoprolol may be employed and used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available. At doses ?20 mg/day, slight asymptomatic increases in airway resistance and decreases in forced expiratory volume (FEV1) has been observed.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition. Patients should be stabilized on heart failure regimen prior to initiation of beta-blocker. Beta-blocker therapy should be initiated at very low doses with gradual and very careful titration. Adjustment of other medications (ACE inhibitors and/or diuretics) may be required
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment required with severe impairment.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required with Clcr <40 mL/minute.
• Thyrotoxicosis: Beta-blockade may mask signs of hyperthyroidism (eg, tachycardia). Abrupt discontinuation of beta-blockade may exacerbate symptoms of hyperthyroidism and may also induce thyroid storm.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving anesthetic agents which decrease myocardial function (eg, ether, cyclopropane, and trichloroethylene).
• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block may occur.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
Adverse Reactions
1% to 10%:
Cardiovascular: Chest pain (1% to 2%)
Central nervous system: Fatigue (dose related; 6% to 8%), insomnia (2% to 3%), hypoesthesia (1% to 2%)
Gastrointestinal: Diarrhea (dose related; 3% to 4%), nausea (2%), vomiting (1% to 2%)
Neuromuscular & skeletal: Arthralgia, asthenia (dose related; ?2%)
Respiratory: Upper respiratory infection (5%), rhinitis (3% to 4%), sinusitis (dose related; 2%), dyspnea (1% to 2%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abdominal pain, acne, alopecia, angioedema, anxiety, arrhythmia, asthma, back/neck pain, bradycardia (dose related), bronchitis, bronchospasm, BUN/creatinine increased, claudication, cold extremities, confusion (especially in the elderly), congestive heart failure, constipation, coughing, cutaneous vasculitis, cystitis, depression, dermatitis, dizziness, dyspepsia, dyspnea on exertion, eczema, edema, flushing, gastritis, gout, hallucinations, headache, hearing decreased, hyper-/hypoesthesia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypertriglyceridemia, hypotension, impotence, lacrimation (abnormal), leukopenia, libido decreased, malaise, memory loss, muscle cramps, muscle/joint pain, nervousness, ocular pain/pressure, orthostatic hypotension, palpitations, paresthesia, peptic ulcer, Peyronie's disease, pharyngitis, polyuria, positive ANA titers, pruritus, psoriasis, psoriasiform eruption, purpura, rash, renal colic, restlessness, rhythm disturbances, sleep disturbances, somnolence, syncope, taste abnormality, thrombocytopenia, tinnitus, transaminases increased, tremor, twitching, uric acid increased, vasculitis, vertigo, visual disturbances, weight gain, xerostomia
Metabolism/Transport Effects
Substrate of CYP2D6 (minor), 3A4 (major)
Drug Interactions
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification
Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Risk D: Consider therapy modification
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may decrease the metabolism of Lidocaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Propafenone: May decrease the metabolism of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Quinidine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy
Rituximab: Antihypertensives may enhance the hypotensive effect of Rituximab. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Exceptions: Fluvoxamine. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. This is true at higher beta-blockers doses where cardioselectivity is lost. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).
Mechanism of Action
Selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors at doses ?20 mg
Pharmacodynamics/Kinetics
Onset of action: 1-2 hours
Absorption: Rapid and almost complete
Distribution: Widely; highest concentrations in heart, liver, lungs, and saliva; crosses blood-brain barrier; enters breast milk
Protein binding: ~30%
Metabolism: Extensively hepatic; significant first-pass effect (~20%)
Bioavailability: ~80%
Half-life elimination: Normal renal function: 9-12 hours; Clcr <40 mL/minute: 27-36 hours; Hepatic cirrhosis: 8-22 hours
Time to peak: 2-4 hours
Excretion: Urine (50% as unchanged drug, remainder as inactive metabolites); feces (<2%)
Dosage
Oral:
Adults: 2.5-5 mg once daily; may be increased to 10 mg and then up to 20 mg once daily, if necessary
Hypertension (JNC 7): 2.5-10 mg once daily
HF (unlabeled use): Initial: 1.25 mg once daily; maximum recommended dose: 10 mg once daily. Note: Increase dose gradually and monitor for signs and symptoms of CHF.
Elderly: Initial dose: 2.5 mg/day; may be increased by 2.5-5 mg/day; maximum recommended dose: 20 mg/day
Dosing adjustment in renal/hepatic impairment: Clcr <40 mL/minute: Initial: 2.5 mg/day; increase cautiously.
Hemodialysis: Not dialyzable
Monitoring Parameters
Blood pressure, ECG, neurologic status
Dietary Considerations
May be taken without regard to meals.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed, with or without regard to meals. Do not take with antacids. Do not adjust dosage or discontinue medication without consulting prescriber. Take pulse daily (prior to medication) and follow prescriber's instruction about holding medication. If you have diabetes, monitor serum sugar closely (drug may alter glucose tolerance or mask signs of hypoglycemia). May cause fatigue, dizziness, or postural hypotension (use caution when changing position from lying or sitting to standing, when driving, or climbing stairs until response to medication is known); alteration in sexual performance (reversible); or constipation (increased dietary bulk and fluids and exercise may help). Report unresolved swelling of extremities, respiratory difficulty or new cough, unresolved fatigue, unusual weight gain, unresolved constipation, or unusual muscle weakness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (ie, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
Bisoprolol may mask signs and symptoms of hypoglycemia; may potentiate hypoglycemia in a patient with diabetes.
Surgery: The ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat angina, symptomatic arrhythmias, hypertension, or other ACC/AHA Class I guideline indications (Class I recommendation). The guidelines also recommend that beta-blockers be given to patients undergoing vascular surgery who have myocardial ischemia demonstrated during preoperative testing (Class I recommendation). More recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery (Juul, 2006; Yang, 2006). However, the majority of previously published trials suggest a benefit.
Based on available evidence, beta-blockers should be started days to weeks before elective surgery when possible and titrated to a heart rate >65 beats per minute. Additional data suggest that long-acting beta-blockers may be superior to short-acting ones.
Cardiovascular Considerations
Atrial Fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.
Chronic Stable Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.
Heart Failure: Strong evidence supports that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration. In the CIBIS-II trial, bisoprolol (beta-1 selective beta-blocker) improved morbidity and mortality in patients with moderate heart failure (NYHA Class III-IV).
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists for another drug, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, post myocardial infarction, high coronary disease risk, or diabetes. In type-2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
ST-segment Elevation Myocardial Infarction (STEMI): Beta-blockers, without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of STEMI and continued long-term. Oral beta-blockade should be initiated promptly in patients without contraindications (eg, signs of heart failure, evidence of a low-output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade may be considered and given promptly if the patient is experiencing concomitant hypertension or a tachyarrhythmia (Class IIa recommendation).
Unstable Angina/Non-ST-Segment Elevation MI (UA/NSTEMI): In the treatment of UA/NSTEMI, oral beta-blockade should be initiated within the first 24 hours in patients without contraindications (eg, signs of heart failure, evidence of a low-output state, risk of cardiogenic shock, or other beta blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade should only be considered if the patient is experiencing concomitant hypertension upon presentation (Class IIa recommendation).
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Bisoprolol is a cardioselective beta-blocker. Local anesthetic with vasoconstrictor can be safely used in patients medicated with bisoprolol. Nonselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia; this has not been reported for bisoprolol. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Fatigue is common; may cause insomnia, confusion, depression, dizziness, headache, sleep disturbance, vivid dreams, anxiety, restlessness, and decreased concentration
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease the effects of beta-blockers
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Blood pressure and heart rate should be assessed prior to and following first dose and with any change in dosage. Assess for therapeutic effectiveness and adverse effects. Instruct patients with diabetes to monitor glucose levels closely (beta-blockers may alter glucose tolerance). Teach patient proper use, possible side effects/appropriate interventions (hypotension precautions), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as fumarate: 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Bisoprolol Fumarate)
5 mg (30): $32.99
10 mg (30): $35.13
Tablets (Zebeta)
5 mg (30): $91.26
10 mg (30): $91.26
References
Adams KF, Lindenfeld J, Arnold JMO, et al, “HFSA 2006 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2006, 12(1):e1–122. Available at http://www.heartfailureguideline.org
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, The Society of Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons,” J Am Coll Cardiol, 2007, 50(7):1-157. Available at http://content.onlinejacc.org/cgi/reprint/50/7/e1
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 (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),” J Am Coll Cardiol, 2004, 44(3):671-719. Available at http://www.acc.org/qualityandscience/clinical/guidelines/stemi/Guideline1/index.htm
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Fleisher LA, Beckman JA, Brown KA, et al, “ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery,” J Am Coll Cardiol, 2007, 50(17):e159-241.
Gibbons RJ, Abrams J, Chatterjee K, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),” J Am Coll Cardiol, 2003, 41(1):159-68.
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)," available at http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf.
Juul AB, Wetterslev J, Gluud C, et al, “Effect of Perioperative Beta Blockade in Patients With Diabetes Undergoing Major Non-Cardiac Surgery: Randomized Placebo Controlled, Blinded Multicentre Trial. DIPOM Trial Group,” BMJ, 2006, 332(7556):1482.
Lang DM, “Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers,” Drug Saf, 1995, 12(5):299-304.
Lindenauer PK, Pekow P, Wang K, et al, “Perioperative Beta-Blocker Therapy and Mortality After Major Noncardiac Surgery,” N Engl J Med, 2005, 353(4):349-61.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Poldermans D, Boersma E, Bax JJ, et al, “The Effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery,” N Engl J Med, 1999, 341(24):1789-94.
“The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A Randomised Trial,” Lancet, 1999, 353(9146):9-13.
UK Prospective Diabetes Study Group, “Efficacy of Atenolol and Captopril in Reducing Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS 39,” BMJ, 1998, 317(7160):713-20.
Yang H, Raymer K, Butler R, et al, “The Effects of Perioperative Beta-Blockade: Results of the Metoprolol After Vascular Surgery (MaVS) Study, a Randomized Controlled Trial,” Am Hear J, 2006, 152(5):983-90.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
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