Diltiazem is used in the management of Prinzmetal variant angina, chronic stable angina pectoris, supraventricular tachycardias, and hypertension.
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 chronic stable angina pectoris, oral diltiazem appears to be as effective as β-adrenergic blocking agents (e.g., propranolol) and/or oral nitrates; however, oral diltiazem generally should be used in chronic stable angina pectoris only when the patient cannot tolerate adequate doses of or is refractory to these drugs. In short-term, controlled clinical studies in patients with chronic stable angina pectoris, oral diltiazem reduced the frequency of attacks, allowed a decrease in sublingual nitroglycerin dosage, and increased the patient's exercise tolerance. Controlled studies also indicate that concurrent use of oral diltiazem and a β-adrenergic blocking agent in patients with chronic stable angina pectoris may reduce the frequency of attacks and increase exercise tolerance; however, 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. Although concomitant therapy with oral diltiazem, 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.
(See Drug Interactions.)
Oral diltiazem is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Only extended-release formulations are recommended for the management of hypertension.
Calcium-channel blocking agents, such as diltiazem, 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, .
Diltiazem is used in the management of supraventricular tachycardias (SVTs), including rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT) (e.g., tachycardia associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome), and control of rapid ventricular rate in atrial flutter or fibrillation. The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline for the management of adults with supraventricular tachycardia recommends the use of diltiazem in the treatment of various SVTs (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, atrioventricular nodal reentrant tachycardia [AVNRT]); in general, IV diltiazem is recommended for acute treatment while oral diltiazem 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., diltiazem or verapamil) may be considered. Diltiazem should only be used in hemodynamically stable patients who do not have impaired ventricular function.
Paroxysmal Supraventricular Tachycardia
IV diltiazem 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 extranodal accessory pathways (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome). In about 86-88% of patients with PSVT, IV diltiazem produces rapid conversion (usually within 2-3 minutes of the first or second dose) to sinus rhythm; conversion to sinus rhythm appears to be dose related. Limited data indicate that conversion to sinus rhythm may occur spontaneously in 25% of placebo-treated patients with PSVT. Transient ventricular premature complexes may be present following conversion of PSVT to sinus rhythm but appear to be benign and of little clinical importance. While comparative trials have not been performed with IV diltiazem and other calcium-channel blockers, the efficacy rate of IV diltiazem in converting PSVT to sinus rhythm appears to be similar to that of verapamil.
Oral diltiazem also has been used to prevent PSVT, but efficacy of the drug for this condition has not been established.
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 diltiazem may be used. Cardioversion is indicated, however, in hemodynamically unstable patients. IV diltiazem should not be used when atrial flutter or fibrillation is associated with an accessory pathway that has a short refractory period (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome) or with preexcited ventricular complexes or wide QRS complexes, since ventricular tachyarrhythmias, including ventricular fibrillation and cardiac arrest, may be precipitated. Although approximately 95% of patients with atrial flutter or fibrillation respond to direct IV injection of 1 or 2 doses with at least a 20% reduction in ventricular rate and this reduction in heart rate is maintained in at least 83% of patients with continuous IV infusion of the drug, IV diltiazem alone rarely (i.e., less than 10% of patients) converts atrial flutter or fibrillation to normal sinus rhythm; limited data indicate that conversion to sinus rhythm may be dose-related and is not usually seen with recommended doses. Conversion to sinus rhythm after drug therapy is more likely to occur in atrial flutter or atrial fibrillation that is of recent onset (i.e., within 24-48 hours) in patients without structural heart disease.
While comparative trials have not been performed with IV diltiazem and IV digoxin, pharmacokinetic data indicate that diltiazem has a faster onset of action than digoxin and may be more useful for slowing ventricular response in patients with atrial flutter or fibrillation. However, because of the potential negative inotropic effect of diltiazem 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., diltiazem or verapamil) are reserved for the management of atrial fibrillation associated with an acute myocardial infarction when β-blockers are contraindicated or ineffective. (See Uses: Acute Myocardial Infarction.)
Oral diltiazem also has been used to reduce heart rate in patients with atrial fibrillation, but efficacy of the drug for this condition has not been established.
IV diltiazem 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 diltiazem may be used for ongoing management.
IV diltiazem also may be used in patients with multifocal atrial tachycardia (i.e., rapid, irregular rhythm with at least 3 distinct P-wave morphologies), although such arrhythmia is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic drugs. 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) or in whom a precipitating factor cannot be identified. While specific studies have not been performed with IV diltiazem in patients with multifocal atrial tachycardia, the effects of the drug are expected to be similar to that of IV verapamil, which has been shown to have some efficacy in the acute treatment of this arrhythmia. Orally administered diltiazem may be a reasonable choice for chronic suppression of recurrent symptomatic multifocal atrial tachycardia.
Diltiazem 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 suggests there may be a role for diltiazem when β-blocking agents (particularly propranolol) are ineffective.
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, diltiazem or verapamil 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. Diltiazem also may be useful in patients with non-ST-elevation infarction, but only when left-ventricular dysfunction, pulmonary congestion, and congestive heart failure are not present; in such patients, diltiazem can be added to standard therapy after the first 24 hours postinfarction and continued for 1 year if indicated. In patients with first non-Q-wave infarction or first anterior infarction without left-ventricular dysfunction or pulmonary congestion, diltiazem or verapamil may reduce the incidence of reinfarction, but their benefit beyond that of β-adrenergic agents and aspirin is unclear. Evidence from the Multicenter Diltiazem Postinfarction Trial (MDPIT) (Q-wave and non-Q-wave infarction) and the Diltiazem Reinfarction Study (DRS) (non-Q-wave infarction) suggests that patients with non-Q-wave myocardial infarction or those with Q-wave infarction, preserved left-ventricular function, and no clinical evidence of heart failure may benefit from immediate-release diltiazem therapy. However, interpretation of the results of the MDPIT is confounded by the fact that 53 and 55% of placebo- and diltiazem-treated patients, respectively, received β-blockers concomitantly. In addition, at the time these studies were conducted, aspirin therapy for cardiovascular benefit was not as prevalent as it is currently, raising additional uncertainty about the relevance of the findings for contemporary management of acute myocardial infarction. Of particular concern is the detrimental effect of diltiazem on mortality in patients with left-ventricular dysfunction. Therefore, the drug is contraindicated in patients with acute myocardial infarction that is accompanied by left-ventricular dysfunction or congestive heart failure. If β-adrenergic blocking agents are contraindicated or poorly tolerated, diltiazem or verapamil can be considered for secondary prevention as an alternative to β-blockers in patients with preserved left ventricular function.
Diltiazem has been used with good results as an alternative to β-adrenergic blocking agents (e.g., propranolol) for short-term adjunctive therapy in the treatment of tachycardia and tachyarrhythmias in a limited number of patients with hyperthyroidism and/or thyrotoxicosis. Diltiazem hydrochloride (160-480 mg daily in divided doses) has reduced heart rate, blood pressure, and ventricular and supraventricular premature complexes in patients with these conditions. Diltiazem does not affect the underlying disease, which must be treated with antithyroid therapy. While additional study and experience are necessary, diltiazem may be a useful alternative to β-adrenergic blocking agents in patients in whom therapy with these agents is contraindicated or not tolerated.