Diltiazem is used in the management of Prinzmetal variant angina, chronic stable angina pectoris, supraventricular tachycardias, and hypertension.
Diltiazem is used in the management of angina, including chronic stable angina, Prinzmetal variant angina, and unstable angina. Calcium-channel blocking agents (used alone or in combination with nitrates) are considered the drugs of choice for the management of Prinzmetal variant angina. β-Blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina; however, calcium-channel blockers may be substituted or added in patients who do not tolerate or respond adequately to β-blockers. In short-term, controlled clinical studies in patients with chronic stable angina, oral diltiazem reduced the frequency of attacks, allowed a decrease in sublingual nitroglycerin dosage, and increased exercise tolerance. All classes of calcium-channel blockers appear to be equally effective in reducing anginal episodes; however, choice of a specific agent should be individualized since the pharmacologic properties of these drugs differ.
Diltiazem also may be beneficial in patients with unstable angina; experts recommend the use of a nondihydropyridine calcium-channel blocker (e.g., diltiazem, verapamil) for the relief of ongoing or recurrent ischemia when β-blocker therapy is inadequate, not tolerated, or contraindicated in patients with unstable angina who do not have clinically important left ventricular dysfunction, increased risk of cardiogenic shock, or AV block.
Although concurrent use of some calcium-channel blockers and a β-blocker may have beneficial effects in some patients (e.g., reduction of dihydropyridine-induced tachycardia through β-blockade), combined use of diltiazem with a β-blocker generally should be avoided because of the potential adverse effects on AV nodal conduction, heart rate, and cardiac contractility.
(See Drug Interactions: β-Adrenergic Blocking Agents.)
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. Calcium-channel blockers (i.e., diltiazem or verapamil) may be used for the management of atrial fibrillation associated with an acute myocardial infarction (MI) in patients with a β-blocker intolerance.
(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 been used in the early treatment and secondary prevention of acute MI; although these drugs are effective anti-ischemic agents, they have not demonstrated mortality benefits and therefore are generally used as an alternative to β-blockers. A review of 28 randomized controlled studies involving 19,000 patients found no benefit with regard to infarct size, rate of reinfarction, or death when calcium-channel blockers were used during the acute or convalescent phase of ST-segment-elevation MI (STEMI). Although some studies demonstrated a reduced risk of reinfarction when verapamil or diltiazem was administered after MI in patients without left ventricular dysfunction, other studies have not confirmed this finding. Calcium-channel blockers generally are used for their anti-ischemic and blood pressure-reducing properties in the MI setting, and only when β-blockers (which have been shown to reduce mortality after MI) are ineffective, not tolerated, or contraindicated; because the nondihydropyridine calcium-channel blockers (verapamil and diltiazem) can cause substantial negative inotropic effects, their use should be limited to patients without left ventricular dysfunction.
Current expert guidelines state that a calcium-channel blocker may be used to relieve ischemic symptoms, lower blood pressure, or control rapid ventricular response associated with atrial fibrillation in patients with STEMI who are intolerant to β-blockers. A nondihydropyridine calcium-channel blocker (e.g., verapamil or diltiazem) may be used as an alternative to β-blockers for relief of ongoing or recurring ischemia when β-blocker therapy is inadequate, not tolerated, or contraindicated in patients with non-ST-segment-elevation MI (NSTEMI) who do not have clinically important left ventricular dysfunction, increased risk of cardiogenic shock, or AV block. The use of immediate-release nifedipine is generally contraindicated because of the potential for hypotension and reflex sympathetic activation.
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.