Atenolol is used for the management of hypertension, angina, and acute myocardial infarction (MI). The drug also has been used for the management of supraventricular and ventricular tachyarrhythmias, management of acute alcohol withdrawal (in conjunction with a benzodiazepine), and prophylaxis of migraine headache.
The choice of a β-adrenergic blocking agent (β-blocker) depends on numerous factors, including pharmacologic properties (e.g., relative β-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity, lipophilicity), pharmacokinetics, intended use, and adverse effect profile, as well as the patient's coexisting disease states or conditions, response, and tolerance. While specific pharmacologic properties and other factors may appropriately influence the choice of a β-blocker in individual patients, evidence of clinically important differences among the agents in terms of overall efficacy and/or safety is limited. Patients who do not respond to or cannot tolerate one β-blocker may be successfully treated with a different agent.
In the management of hypertension or chronic stable angina pectoris in patients with chronic obstructive pulmonary disease (COPD) or type 1 diabetes mellitus, many clinicians prefer to use low dosages of a β1-selective adrenergic blocking agent (e.g., atenolol, metoprolol), rather than a nonselective agent (e.g., nadolol, pindolol, propranolol, timolol). However, selectivity of these agents is relative and dose dependent. Some clinicians also will recommend using a β1-selective agent or an agent with intrinsic sympathomimetic activity (ISA) (e.g., pindolol), rather than a nonselective agent, for the management of hypertension or angina pectoris in patients with peripheral vascular disease, but there is no evidence that the choice of β-blocker substantially affects efficacy.
Atenolol is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Atenolol's efficacy in hypertensive patients is similar to that of other β-blockers.
Current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics). Although β-blockers were previously considered a drug of choice for the initial management of hypertension, most current guidelines no longer recommend these drugs as first-line therapy because of the lack of established superiority over other recommended drug classes and at least one study demonstrating that they may be less effective than angiotensin II receptor antagonists in preventing cardiovascular death, MI, or stroke. However, β-blockers may still be considered in hypertensive patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes. Ultimately, choice of antihypertensive therapy should be individualized, considering the clinical characteristics of the patient (e.g., age, ethnicity/race, comorbid conditions, cardiovascular risk factors) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, costs). Because many patients eventually will need drugs from 2 or more antihypertensive classes, experts generally state that the emphasis should be placed on achieving appropriate blood pressure control rather than on identifying a preferred drug to achieve that control.
Considerations in Initiating Antihypertensive Therapy
Drug therapy generally is reserved for patients who respond inadequately to nondrug therapy (i.e., lifestyle modifications such as diet [including sodium restriction and adequate potassium and calcium intake], regular aerobic physical activity, moderation of alcohol consumption, and weight reduction) or in whom the degree of blood pressure elevation or coexisting risk factors requires more prompt or aggressive therapy; however, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.
While the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended antihypertensive drug therapy in all patients with systolic/diastolic blood pressure of 140/90 mm Hg or higher who fail to respond to lifestyle/behavioral modifications, other experts, including the panel members appointed to the Eighth Joint National Committee (JNC 8 expert panel) currently recommend a higher systolic blood pressure threshold for older individuals (e.g., the JNC 8 expert panel recommends a threshold of 150 mm Hg for patients 60 years of age or older).
In addition, there is some variation in the blood pressure thresholds and treatment goals recommended for patients with diabetes mellitus or chronic kidney disease. In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had blood pressures of 130/80 mm Hg or higher; however, current hypertension management guidelines generally recommend the same blood pressure threshold of 140/90 mm Hg for initiating antihypertensive drug therapy in these individuals as for the general population of patients without these conditions, although a lower goal (e.g., less than 130/80 mm Hg) may still be considered.
Further study is needed to more clearly define optimum blood pressure goals in patients with hypertension; when determining appropriate blood pressure goals, individual risks and benefits should be considered in addition to the evidence from clinical studies.
Antihypertensive drug therapy generally should be initiated gradually and titrated at intervals of approximately 2-4 weeks to achieve the target blood pressure. The goal is to reduce blood pressure to levels below the threshold used for initiating drug therapy. Addition of a second drug should be initiated when use of monotherapy in adequate dosages fails to achieve goal blood pressure. Some experts state that initial antihypertensive therapy with a combination of drugs may be considered in patients with systolic/diastolic blood pressure greater than 20/10 mm Hg above goal blood pressure. Such combined therapy may increase the likelihood of achieving goal blood pressure in a more timely fashion, but also may increase the risk of adverse effects (e.g., orthostatic hypotension) in some patients (e.g., elderly). Initial combined therapy may be particularly useful in patients with markedly high baseline blood pressures and those with additional risk factors.
Initial Drug Therapy
For initial antihypertensive drug therapy, experts currently recommend a thiazide diuretic, calcium-channel blocker, ACE inhibitor, or angiotensin II receptor antagonist. β-Blockers generally are not preferred for initial monotherapy in patients with uncomplicated hypertension, but may be beneficial in patients with a compelling indication (e.g., ischemic heart disease, atrial tachyarrhythmias, history of MI, heart failure) for their use.
Follow-up and Maintenance Therapy
Several strategies are recommended for the titration and combination of antihypertensive drugs; these strategies include maximizing the dosage of the first drug before adding a second drug, adding a second drug before achieving maximum dosage of the initial drug, or initiating therapy with 2 drugs simultaneously (either as separate preparations or as a fixed-dose combination). If goal blood pressure is not achieved with initial monotherapy with one of the recommended antihypertensive drug classes, a second drug from one of the recommended drug classes may be added; if goal blood pressure is not achieved with optimal dosages of 2 antihypertensive agents, a third antihypertensive agent from one of the recommended drug classes may be added. If more than 3 drugs are required, other antihypertensive drug classes, including β-blockers, may be considered. If the blood pressure goal cannot be achieved with the above recommended strategies, consultation with a hypertension specialist should be considered.
Thus, atenolol can be used for the management of hypertension as initial monotherapy (not usually preferred, but may be used in patients with a compelling indication) or as a component of a multiple-drug regimen. β-Blockers often are used concurrently with a diuretic because of their additive effects. β-Blockers also have been combined with vasodilators (e.g., hydralazine, minoxidil) to counteract the reflex tachycardia that occurs with vasodilators.
Antihypertensive Therapy for Patients with Underlying Cardiovascular or Other Risk Factors
Drug therapy in patients with hypertension and underlying cardiovascular or other risk factors should be carefully individualized based on the underlying disease(s), concomitant drugs, tolerance to drug-induced adverse effects, and blood pressure goal.
Ischemic Heart Disease
The selection of an appropriate antihypertensive agent in patients with ischemic heart disease should be based on individual patient characteristics, but may include a β-blocker, with the addition of other drugs (e.g., ACE inhibitors, thiazide diuretics, calcium-channel blockers) as necessary to achieve blood pressure goals. Because of the demonstrated mortality benefit of β-blockers following MI, these drugs should be administered in all patients who have survived an MI.
While β-blockers as single therapies are not superior to other antihypertensive agents in the reduction of all cardiovascular outcomes, certain β-blockers have been shown to be effective in reducing the incidence of heart failure and associated morbidity and mortality.
Other Special Considerations for Antihypertensive Therapy
In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blocking agents than to monotherapy with β-blockers, ACE inhibitors, or angiotensin II receptor antagonists. However, such diminished response to a β-blocker is largely eliminated when the drug is administered concomitantly with a thiazide diuretic. In addition, some experts state that when use of β-blockers is indicated in hypertensive patients with underlying cardiovascular or other risk factors, these indications should be applied equally to black hypertensive patients.
For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults in the Thiazides General Statement 40:28.20.
Chronic Stable Angina
Atenolol is used for the management of chronic stable angina pectoris. β-Blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this indication. Long-term use of β-blockers in patients with chronic stable angina pectoris has been shown to reduce the frequency of anginal attacks, allow a reduction in nitroglycerin dosage, and increase exercise tolerance.
Combination therapy with a β-blocker and a nitrate appears to be more effective than either drug alone because β-blockers attenuate the increased sympathetic tone and reflex tachycardia associated with nitrate therapy while nitrate therapy (e.g., nitroglycerin) counteracts the potential increase in left-ventricular wall tension associated with a decrease in heart rate. Combined therapy with a β-blocker and a dihydropyridine calcium-channel blocker also may be useful because the tendency to develop tachycardia with the calcium-channel blocker is counteracted by the β-blocker. However, caution should be exercised in the concomitant use of β-blockers and the nondihydropyridine calcium-channel blockers verapamil or diltiazem because of the potential for excessive fatigue, bradycardia, or atrioventricular (AV) block.
(See Drug Interactions: Cardiovascular Drugs.)
Non-ST-Segment-Elevation Acute Coronary Syndromes
β-Blockers are used as part of the standard therapeutic measures for managing non-ST-segment-elevation acute coronary syndromes (NSTE ACS). Patients with NSTE ACS have either unstable angina or non-ST-segment-elevation MI (NSTEMI); because these conditions are part of a continuum of acute myocardial ischemia and have indistinguishable clinical features upon presentation, the same initial treatment strategies are recommended. The American Heart Association/American College of Cardiology (AHA/ACC) guideline for the management of patients with NSTE ACS recommends an early invasive strategy (angiographic evaluation with the intent to perform revascularization procedures such as percutaneous coronary intervention [PCI] with coronary artery stent implantation or coronary artery bypass grafting [CABG]) or an ischemia-guided strategy (initial medical management followed by cardiac catheterization and revascularization if indicated) in patients with definite or likely NSTE ACS; standard medical therapies for all patients should include a β-blocker, antiplatelet agents (aspirin and/or a P2Y12-receptor antagonist), anticoagulant agents (e.g., low molecular weight or unfractionated heparin), nitrates (e.g., nitroglycerin), and analgesic agents regardless of the initial management approach. The guideline states that oral β-blocker therapy should be initiated within the first 24 hours in patients who do not have manifestations of heart failure, evidence of a low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy; use of IV β-blockers is potentially harmful in patients with risk factors for cardiogenic shock. Continued therapy with a β-blocker proven to reduce mortality (bisoprolol, carvedilol, or metoprolol succinate) is recommended in patients with stabilized heart failure and reduced systolic function.
Acute Myocardial Infarction
Atenolol is used to reduce the risk of cardiovascular mortality in hemodynamically stable patients with definite or suspected acute MI. The term MI is used when there is evidence of myocardial necrosis in the setting of acute myocardial ischemia. ST-segment-elevation MI (STEMI) is distinguished from NSTEMI based on the presence or absence of ST-segment elevation on ECG. Patients with STEMI typically have complete arterial occlusion; therefore, immediate reperfusion therapy (with primary PCI or thrombolytic agents) is the current standard of care for such patients. Because the clinical presentation of NSTEMI is similar to that of unstable angina, these conditions are considered together in current expert guidelines.
(See Uses: Non-ST-Segment-Elevation Acute Coronary Syndromes.)During the early stage of a definite or suspected MI, atenolol has been initiated with IV doses (no longer commercially available in the US), followed by continued oral dosing; however, experts currently recommend that early IV use of β-blockers be limited to selected patients.
Because β-blockers can reduce myocardial oxygen demand during the first few hours of an acute MI by reducing heart rate, arterial blood pressure, and myocardial contractility, and also have been shown to reduce mortality, early IV therapy with these drugs was routinely recommended following acute MI. Evidence supporting this recommendation was generally based on studies conducted prior to the reperfusion era demonstrating a reduction in mortality and other clinical benefits (i.e., reduced infarct size, incidence of ventricular arrhythmias, chest pain, and cardiac enzyme elevations) with early use of β-blockers during MI. In one such study (the First International Study of Infarct Survival; ISIS-1), therapy with atenolol (initiated IV within the first 12 hours of symptom onset and continued orally for 7 days) was shown to reduce cardiovascular mortality by approximately 15% during the first few days of therapy, but did not substantially reduce cardiovascular mortality beyond this initial period. The difference in vascular mortality rate between those receiving atenolol or placebo was evident almost entirely during the first 2 days of therapy. Analysis of data from a subset of patients who died during early treatment in ISIS-1 suggested that the principal mechanism of early mortality reduction associated with atenolol therapy was prevention of cardiac rupture and of cardiac electromechanical dissociation. However, the relevance of these study findings to current clinical practice has been questioned since patients did not receive reperfusion therapy and only 5% received an antiplatelet agent.
Studies conducted after the widespread use of reperfusion therapy generally have demonstrated more attenuated benefits with early β-blocker therapy in patients with acute MI; while β-blockers may still confer benefits (e.g., reduction in the risk of reinfarction and ventricular arrhythmias), there is less certainty regarding the drugs' effects on mortality in patients receiving contemporary revascularization and pharmacologic therapies (antiplatelet agents, ACE inhibitors, and lipid-lowering therapies). In addition, early use of β-blockers (particularly when administered IV) has been associated with an increased risk of cardiogenic shock. Based on the currently available evidence, the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the management of STEMI recommends oral β-blocker therapy in all patients who do not have manifestations of heart failure, evidence of a low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy. Such therapy should be initiated within the first 24 hours following acute MI and continued during and after hospitalization. Because of conflicting evidence of benefit and the potential for harm, the guidelines recommend limiting use of IV β-blockers to patients with refractory hypertension or ongoing ischemia.
Although the efficacy of atenolol in reducing cardiovascular mortality has been established only during the first 7 days after an acute MI, the benefits of long-term β-blocker therapy for secondary prevention have been well established in numerous clinical studies. Patients with MI complicated by heart failure, left ventricular dysfunction, or ventricular arrhythmias appear to derive the most benefit from long-term β-blocker therapy. Data from studies using other β-blockers suggest that optimum benefit may be achieved if treatment with these agents is continued for at least 1-3 years if not indefinitely after infarction unless contraindicated. Several large, randomized studies have demonstrated that prolonged oral therapy with a β-blocker can reduce the rates of reinfarction and mortality (e.g., sudden and nonsudden cardiac death) following acute MI. It is estimated that such therapy could result in a relative reduction in mortality of about 25% annually for years 1-3 after infarction, with high-risk patients exhibiting the greatest potential benefit; the benefit of continued therapy may persist for at least several years beyond this period, although less substantially. Therefore, atenolol, like other β-blockers, can be used for secondary prevention following acute MI to reduce the risk of reinfarction and mortality. The AHA/ACCF secondary prevention guideline recommends β-blocker therapy in all patients with left ventricular systolic dysfunction (ejection fraction of 40% or less) and a prior MI; use of a β-blocker with proven mortality benefit (bisoprolol, carvedilol, or metoprolol succinate) is recommended. Although the benefits of long-term β-blockade in post-MI patients with normal left ventricular function are less well established, the guideline recommends continued β-blocker therapy for at least 3 years in such patients. Further studies are needed to establish the optimal duration of β-blocker therapy for secondary prevention of MI.
β-Blockers, including atenolol, have been used to slow ventricular rate in patients with supraventricular tachycardia (SVT). The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline for the management of adult patients with supraventricular tachycardia recommends the use of β-adrenergic blocking agents in the treatment of various SVTs (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, atrioventricular nodal reentrant tachycardia [AVNRT]); in general, an IV β-blocker is recommended for acute treatment, while an oral preparation is recommended for ongoing management of these arrhythmias. Vagal maneuvers and/or IV adenosine are considered first-line interventions for the acute treatment of patients with SVT and should be attempted prior to other therapies when clinically indicated; if such measures are ineffective or not feasible, an IV β-blocker may be considered in hemodynamically stable patients. Although evidence of efficacy is limited, experts state that the overall safety of β-adrenergic blockers warrants their use in patients with SVT. Patients should be closely monitored for hypotension and bradycardia during administration of these drugs.
Atrial Fibrillation and Flutter
β-Blockers are recommended as one of several drug therapy options for ventricular rate control in patients with nonpreexcited atrial fibrillation or flutter. For acute treatment of atrial fibrillation or flutter, an IV β-adrenergic blocking agent (e.g., esmolol, propranolol, metoprolol) may be used for ventricular rate control in patients without preexcitation; an oral β-blocker such as atenolol may be used for ongoing rate control in such patients. Choice of a specific β-blocker should be individualized based on the patient's clinical condition.
IV β-blockers may be used for the treatment of patients with hemodynamically stable focal atrial tachycardia (i.e., regular SVT arising from a localized atrial site), and an oral β-blocker may be used for ongoing management. Multifocal atrial tachycardia, characterized by a rapid, irregular rhythm with at least 3 distinct P-wave morphologies, is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic drug therapy. Antiarrhythmic drug therapy usually is reserved for patients who do not respond to initial attempts at correcting or managing potential precipitating factors (e.g., exacerbation of chronic obstructive pulmonary disease or congestive heart failure, hypoxemia, anemia) or in whom a precipitating factor cannot be identified.
Paroxysmal Supraventricular Tachycardia
IV β-blockers may be used for the acute treatment of hemodynamically stable patients with paroxysmal supraventricular tachycardia (PSVT), including AVNRT, that is uncontrolled or unconverted by vagal maneuvers and adenosine; an oral β-blocker may be used for the ongoing management of such patients who are not candidates for, or prefer not to undergo, catheter ablation.
β-Blockers are considered one of several drug therapy options that may be used for the treatment of junctional tachycardia (i.e., nonreentrant SVT originating from the AV junction), a rapid, occasionally irregular, narrow-complex tachycardia. While evidence is limited, there is some data indicating that β-blockers (specifically propranolol) are modestly effective in terminating and/or reducing the incidence of junctional tachycardia.
β-Blockers also have been used in patients with cardiac arrest precipitated by ventricular fibrillation or pulseless ventricular tachycardia. However, AHA states that routine administration of β-blockers after cardiac arrest is potentially harmful (e.g., may worsen hemodynamic instability, exacerbate heart failure, or cause bradyarrhythmias) and is therefore not recommended.
β-Blockers may be useful in the management of certain forms of polymorphic ventricular tachycardia (e.g., associated with acute ischemia).
Atenolol has been used for the prophylaxis of migraine headache. When used prophylactically, atenolol can prevent migraine or reduce the number of attacks in some patients. However, the US Headache Consortium states that the quality of evidence for atenolol is not as compelling as it is for propranolol for this indication. Atenolol is not recommended for the treatment of a migraine attack that has already started. For further information on management and classification of migraine headache,
Atenolol has been used in conjunction with a benzodiazepine in the management of acute alcohol withdrawal. β-Blockers such as atenolol appear to be effective in reducing manifestations of the hyperadrenergic state associated with alcohol withdrawal, including elevated blood pressure, increased heart rate, and anxiety. However, β-blockers have not been shown to prevent delirium or seizures, and such drugs should be used only as adjuncts to benzodiazepines (not as monotherapy) for the treatment of alcohol withdrawal. Some clinicians state that the use of β-blockers may be particularly helpful in patients with certain coexisting conditions (e.g., coronary artery disease).