Verapamil is used in the management of supraventricular tachycardias (SVTs). The drug also is used for the management of Prinzmetal variant angina and unstable and chronic stable angina pectoris, and for the management of hypertension.
Verapamil is used for rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including tachycardia associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome; the drug also is used for control of rapid ventricular rate in nonpreexcited atrial flutter or fibrillation. 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 verapamil in the treatment of various SVTs (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, atrioventricular nodal reentrant tachycardia [AVNRT]); in general, IV verapamil is recommended for acute treatment, while oral verapamil 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, a nondihydropyridine calcium-channel blocker (i.e., verapamil or diltiazem) may be considered. Verapamil should only be used in hemodynamically stable patients who do not have impaired ventricular function.
Paroxysmal Supraventricular Tachycardia
IV verapamil is used for rapid conversion of PSVT that is uncontrolled or unconverted by vagal maneuvers and adenosine, including atrioventricular nodal reentrant tachycardias and PSVT associated with accessory bypass tracts (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome). In 60-100% of patients with PSVT, rapid (usually within 10 minutes after administration) conversion to sinus rhythm is achieved with IV verapamil.
Verapamil is used orally to prevent recurrent PSVT and is considered a drug of choice for this arrhythmia. The drug appears to be more effective in preventing PSVT associated with AV nodal reentry than that associated with a concealed accessory pathway.
Atrial Fibrillation and Flutter
Nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) are recommended as one of several drug therapy options for ventricular rate control in patients with nonpreexcited atrial fibrillation or flutter. Management of atrial fibrillation or flutter depends on the clinical situation and the patient's condition. For acute treatment of atrial fibrillation, IV verapamil may be used to temporarily control rapid ventricular rate, usually decreasing heart rate by at least 20%. Cardioversion is indicated, however, in hemodynamically unstable patients. Verapamil should not be used when atrial flutter or fibrillation (especially when preexcited ventricular complexes are present) is associated with an accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome), since ventricular tachyarrythmias, including ventricular fibrillation, and cardiac arrest may be precipitated.
(See Cautions: Cardiovascular Effects.)Although approximately 70% of patients with atrial flutter and/or fibrillation respond to IV verapamil with a reduction in ventricular rate, the drug alone rarely converts atrial flutter or fibrillation to normal sinus rhythm. Conversion is more likely to occur in atrial flutter or fibrillation that is of recent onset and/or associated with only mild or moderate left-atrial enlargement.
Because of the potential negative inotropic effect of verapamil and recent concerns about the use of calcium-channel blockers in acute myocardial infarction
(see Cautions: Precautions and Contraindications), these drugs are not recommended as first-line agents following an acute myocardial infarction despite their efficacy in slowing heart rate, especially in patients already receiving a β-adrenergic blocking agent. Generally, calcium-channel blockers (i.e., verapamil or diltiazem) are reserved for the management of atrial fibrillation associated with acute myocardial infarction when β-blockers are contraindicated or ineffective. (See Uses: Acute Myocardial Infarction.)
Oral verapamil is used in conjunction with a cardiac glycoside (e.g., digoxin) to control ventricular rate at rest and during stress in patients with chronic atrial fibrillation and/or flutter. Verapamil has also been used alone and in combination with quinidine to control ventricular rate in these patients. The drug should not be used when these arrhythmias are associated with an accessory bypass tract. Unlike cardiac glycosides, verapamil may be particularly useful in controlling tachycardia induced by exercise and stress. Verapamil reduces heart rate at rest (e.g., by 15-30%) and increases exercise capacity in patients with chronic atrial fibrillation and/or flutter, and has been effective in patients who did not respond adequately to a cardiac glycoside alone. Improvement in maximal exercise capacity occurs with a concomitant decrease in heart rate, blood pressure, and double product (heart rate times systolic blood pressure) at maximal exertion during verapamil therapy. Combined therapy with verapamil and a cardiac glycoside appears to be somewhat more effective than verapamil or a cardiac glycoside alone. Cardioversion has been used safely and effectively following IV or oral verapamil administration.
Although controlled studies have not been conducted to date, IV verapamil also has been used successfully in the management of PSVT and atrial fibrillation or flutter in neonates and children. However, most experts state that verapamil should not be used in infants because it may cause refractory hypotension and cardiac arrest and should be used with caution in children because it may cause hypotension and myocardial depression.
(see Cautions: Pediatric Precautions.)
IV verapamil may be used for the acute treatment of patients with hemodynamically stable focal atrial tachycardia (i.e., regular SVT arising from a localized atrial site), and oral verapamil may be used for ongoing management.
While evidence is more limited, IV verapamil also has been used in patients with multifocal atrial tachycardia (i.e., rapid, irregular rhythm with at least 3 distinct P-wave morphologies) to control ventricular rate and convert to normal sinus rhythm. However, such arrhythmia is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic 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, electrolyte and/or ventilatory disturbances, infection, theophylline toxicity). Therapy with verapamil has been associated with slowing of atrial and ventricular rates and conversion to sinus rhythm in some patients with this arrhythmia. Therefore, some clinicians suggest that IV verapamil may be useful for the acute treatment of patients with multifocal atrial tachycardia who do not have ventricular dysfunction, sinus node dysfunction, or AV block. Verapamil also may be useful orally for chronic suppression of recurrent symptomatic multifocal atrial tachycardia.
Verapamil 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. β-Adrenergic blocking agents generally are used for acute termination and/or ongoing management of junctional tachycardia; limited evidence suggest there may be a role for verapamil when β-blocking agents (particularly propranolol) are ineffective.
Oral calcium-channel blocking agents are considered the drugs of choice for the management of Prinzmetal variant angina. A nondihydropyridine calcium-channel blocker (e.g., diltiazem, verapamil) also has been recommended in patients with unstable angina who have continuing or ongoing ischemia when therapy with β-blocking agents and nitrates is inadequate, not tolerated, or contraindicated and when severe left ventricular dysfunction, pulmonary edema, or other contraindications are not present. In the management of unstable or chronic stable angina pectoris, verapamil appears to be as effective as β-adrenergic blocking agents (e.g., propranolol) and/or oral nitrates. In unstable or chronic stable angina pectoris, verapamil may reduce the frequency of attacks, allow a decrease in sublingual nitroglycerin dosage, and increase the patient's exercise tolerance. Although evidence suggests that concurrent use of verapamil and a β-adrenergic blocking agent may be beneficial in patients with unstable or chronic stable angina pectoris, additional study is needed to determine the safety and efficacy of concomitant therapy, especially in patients with compromised left ventricular function or cardiac conduction abnormalities.
(See Drug Interactions: β-Adrenergic Blocking Agents.)Although concomitant therapy with verapamil, nitroglycerin, and a β-adrenergic blocking agent may be beneficial in some patients, the safety and/or efficacy of such therapy have not been fully determined.
Verapamil is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.
Calcium-channel blocking agents (e.g., verapamil) are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.
Calcium-channel blockers may be particularly useful in the management of hypertension in black patients; these patients tend to have greater blood pressure response to calcium-channel blockers and thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists). Use of a calcium-channel blocker also may be beneficial in patients with certain coexisting conditions such as ischemic heart disease (e.g., angina) and in geriatric patients, including those with isolated systolic hypertension. In addition, nondihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) may be beneficial in hypertensive patients with coexisting atrial fibrillation and a rapid ventricular rate.
In the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study, the long-term cardiovascular morbidity and mortality benefit of a long-acting dihydropyridine calcium-channel blocker (amlodipine), a thiazide-like diuretic (chlorthalidone), and an ACE inhibitor (lisinopril) were compared in a broad population of patients with hypertension at risk for coronary heart disease. Although these antihypertensive agents were comparably effective in providing important cardiovascular benefit, apparent differences in certain secondary outcomes were observed. Patients receiving the ACE inhibitor experienced higher risks of stroke, combined cardiovascular disease, GI bleeding, and angioedema, while those receiving the calcium-channel blocker were at higher risk of developing heart failure. The ALLHAT investigators suggested that the favorable cardiovascular outcome may be attributable, at least in part, to the greater antihypertensive effect of the calcium-channel blocker compared with that of the ACE inhibitor, especially in women and black patients.
For additional information on the role of calcium-channel blockers in the management of hypertension, . For information on overall principles and expert recommendations for treatment of hypertension,
Verapamil has been used as adjunctive therapy in the management of hypertrophic cardiomyopathy. The drug is used to relieve cardiac manifestations (e.g., angina, dyspnea) and improve exercise capacity and quality of life associated with cardiomyopathy-induced outflow tract obstruction and also may alleviate and suppress concomitant supraventricular tachyarrhythmias. Verapamil therapy also has produced clinical improvement in patients without evidence of outflow obstruction. The drug can reduce the outflow tract gradient in patients with obstruction and enhance left ventricular diastolic filling (e.g., rate) and relaxation; the drug also appears to reduce regional systolic and diastolic asynchrony. In addition, limited evidence suggests that verapamil may limit the extent of ischemic myocardial changes in some patients with hypertrophic cardiomyopathy; however, the drug may not alter the underlying hypertrophic process, which apparently can progress slowly despite clinical and cardiac functional improvements induced by the drug and evidence of an increase in the number of calcium-channel blocking agent receptors (1,4-dihydropyridine receptors) in the myocardium of patients with this condition.
While clinical improvement frequently occurs in patients with hypertrophic cardiomyopathy treated with verapamil, improvement in the extent of hypertrophy as evidenced by changes in intraventricular septum (IVS) and left ventricular posterior wall (LVPW) thickness and in left ventricular diameters appears to occur only occasionally. In one study, there was no change in these parameters overall in patients receiving verapamil, although 13% of these patients exhibited decreases in IVS and/or LVPW thickness. The clinical importance of such changes is not known, but some evidence suggests that decreases in LVPW thickness in patients with hypertrophic cardiomyopathy actually may result in left ventricular systolic dysfunction.
Despite evidence of a lack of substantial effect on the underlying hypertrophic process, functional cardiac changes induced by verapamil, particularly those involving left ventricular diastolic filling, relaxation, and asynchrony, can result in decreased ischemic manifestations, including symptomatic improvement and increased exercise tolerance. While the role of chronic drug therapy in asymptomatic patients with hypertrophic cardiomyopathy remains controversial, verapamil has improved reversible perfusion defects and exercise capacity in such patients, and some clinicians suggest that such therapy can be considered for relatively young patients with a family history of premature sudden death and those with marked ventricular hypertrophy or marked subaortic stenosis.
Verapamil appears to be more effective than propranolol as adjunctive therapy in the management of hypertrophic cardiomyopathy and often is effective and can delay the need for surgery in patients who fail to respond to β-adrenergic blocker therapy. In one study, most such patients improved clinically following discontinuance of propranolol and initiation of verapamil, and in many of those in whom symptoms were considered severe enough to warrant surgery, improvement was sufficient to delay the need for surgery. In another comparative study, clinical and hemodynamic improvement was greater with verapamil than with propranolol. However, because response to drug therapy in patients with hypertrophic cardiomyopathy is variable, probably secondary to the complexity and relative contribution of various underlying pathophysiologic mechanisms in this condition, such therapy should be individualized.
Additional study and experience are necessary to determine whether the beneficial effects of verapamil in hypertrophic cardiomyopathy persist during long-term therapy. Some evidence suggests that potential benefits may diminish with time. In addition, verapamil should be used for hypertrophic cardiomyopathy with extreme caution and only when other alternatives are not considered suitable in patients with elevated pulmonary venous pressures (particularly when combined with a baseline outflow obstruction), paroxysmal nocturnal dyspnea or orthopnea, or clinically important SA nodal or AV junctional conduction abnormalities (unless a functional artificial ventricular pacemaker is in place).
Acute Myocardial Infarction
Calcium-channel blocking agents have not proved beneficial in the early treatment or secondary prevention of acute myocardial infarction, and the possibility that they may be harmful has been raised.
(See Cautions: Precautions and Contraindications.)However, verapamil or diltiazem generally can be used after an acute myocardial infarction when β-adrenergic blocking agents are ineffective or contraindicated for the relief of ongoing ischemia or to control rapid ventricular response with atrial fibrillation, but only in patients in whom there is no evidence of congestive heart failure, left-ventricular dysfunction, or AV block and only after weighing carefully the potential benefits versus risks, particularly negative inotropic effects and recent concerns about short-acting formulations of the drugs. In patients with first non-Q-wave infarction or first anterior infarction without left-ventricular dysfunction or pulmonary congestion, verapamil or diltiazem may reduce the incidence of reinfarction, but their benefit beyond that of β-adrenergic agents and aspirin is unclear. Although a clear mortality benefit has not been demonstrated, subgroup analysis of clinical trials indicates that immediate-release verapamil initiated several days after acute myocardial infarction in patients who were not candidates for β-blocker therapy may be beneficial in reducing the incidence of combined endpoint of reinfarction and death, provided that left-ventricular function is well preserved and there is no clinical evidence of heart failure. In one large study in patients younger than 75 years of age, verapamil initiated within 2 weeks after acute myocardial infarction decreased major endpoints (death or reinfarction) over 18 months. Therefore, if β-adrenergic blocking agents are contraindicated or poorly tolerated, verapamil or diltiazem can be considered for secondary prevention as an alternative to β-blockers in patients with preserved left ventricular function. Verapamil is detrimental to patients with heart failure or bradyarrhythmias during the initial 24-48 hours after infarction. The drug is contraindicated in patients with acute myocardial infarction that is accompanied by left-ventricular dysfunction or congestive heart failure. (See Cautions: Precautions and Contraindications.)
Verapamil has been used orally with some success in a limited number of patients for the management of manic manifestations of bipolar disorder, but additional study is needed.