Nifedipine is used in the management of Prinzmetal variant angina and chronic stable angina pectoris. 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-Adrenergic blocking agents (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 controlled clinical studies of up to 8 weeks' duration in patients with chronic stable angina, nifedipine 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. The potential risks of short-acting (conventional, immediate-release) nifedipine should be considered.
Calcium-channel blockers also have been used for the relief of ongoing or recurrent ischemia in patients with unstable angina; however, a nondihydropyridine calcium-channel blocker (e.g., diltiazem, verapamil) generally is recommended.
Concurrent use of nifedipine and a β-blocker may have beneficial effects in some patients with chronic stable angina (e.g., reduction of dihydropyridine-induced tachycardia through β-blockade).
Nifedipine is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Because of concerns about potentially serious adverse cardiovascular effects and increased mortality associated with short-acting (conventional, immediate-release) nifedipine
(see Cautions), only extended-release formulations of the drug are recommended for the management of hypertension.
Calcium-channel blocking agents (e.g., nifedipine) 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 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 of 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, see . For information on overall principles and expert recommendations for treatment of hypertension, .
In the past, when oral therapy was considered preferable to parenteral therapy in selected patients, short-acting (conventional, immediate-release capsules) nifedipine had been used for rapidly reducing blood pressure in patients with hypertensive crises in whom reduction of blood pressure was considered urgent (hypertensive urgencies) or an emergency (hypertensive emergencies); however, most clinicians and the manufacturers now question the safety of short-acting nifedipine for this use because of occasional reports of poorly tolerated severe hypotension and the potential adverse cardiovascular consequences (e.g., cerebrovascular ischemia, stroke, myocardial ischemia and infarction, death). As a result of these and other
(see Cautions)concerns and absence of substantial evidence clearly establishing superiority (both in terms of safety and efficacy) of nifedipine for this use, it is recommended that short-acting nifedipine no longer be used for the management of any form of hypertension, including hypertensive crises.
Patients with hypertensive emergencies (i.e., those rare situations requiring immediate blood pressure reduction, although not necessarily to normal ranges, in order to prevent or limit target organ damage) require hospitalization and are treated with an appropriate parenteral antihypertensive agent (e.g., labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside). Hypertensive urgencies (i.e., situations in which there is severe elevation in blood pressure without progressive target organ damage) generally can be managed by intensification or reinstitution (e.g., following noncompliance) of the current antihypertensive regimen or with oral doses of short-acting antihypertensive agents (e.g., captopril, labetalol, clonidine) followed by several hours of observation. However, there is no evidence suggesting that failure to aggressively reduce blood pressure in these patients is associated with any short-term risk. In fact, overly aggressive management of severe elevations in blood pressure not associated with impending or progressing organ damage can sometimes lead to cumulative hypotensive effects. Excessive falls in blood pressure should be avoided in any hypertensive crisis since they may precipitate renal, cerebral, or coronary ischemia.
Hypertension During Pregnancy
Antihypertensive therapy is recommended in pregnant women with chronic hypertension who have persistent, severely elevated blood pressure (e.g., systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 105 mm Hg or higher); it is less clear whether antihypertensive therapy should be initiated in women with mild to moderate chronic hypertension. If initiation of antihypertensive therapy is necessary in a pregnant woman, use of labetalol, nifedipine, or methyldopa is recommended by the American College of Obstetricians and Gynecologists (ACOG) and other experts. In women who are already receiving antihypertensive therapy prior to pregnancy, ACOG states there are insufficient data to make recommendations regarding the continuance or discontinuance of such therapy; treatment decisions should be individualized in these situations.
Nifedipine also has been used orally in the hospital setting for urgent lowering of blood pressure in severely hypertensive pregnant women, including those with preeclampsia. However, short-acting (conventional) formulations of nifedipine are not labeled by the US Food and Drug Administration (FDA) for acute reduction of blood pressure; cases of profound hypotension and other serious adverse cardiovascular consequences have been reported with the use of these preparations. (For additional information on the use of antihypertensive drugs in women with preeclampsia,
Nifedipine has been used effectively in the management of Raynaud's phenomenon and is considered a drug of choice for the management of this condition. The drug has reduced the frequency, duration, and severity of attacks in patients with this condition. However, not all patients with this condition respond to nifedipine, and intolerable adverse effects (e.g., headache, flushing, orthostatic hypotension) may limit the usefulness of the drug in some other patients. Although most experience with nifedipine in the management of Raynaud's phenomenon had been with short-acting (conventional, immediate-release) formulations of the drug, recent concerns (e.g., risks of serious hypotension and associated cardiovascular consequences) about the safety of short-acting (conventional) nifedipine have prompted the manufacturers to warn against use of this preparation in conditions for which safety and efficacy have not been fully established.
(See Cautions.)Therefore, while not studied as extensively as short-acting nifedipine, extended-release nifedipine (e.g., 30-60 mg daily) preferably should be used when the drug is indicated for the management of Raynaud's phenomenon. The extended-release preparation of nifedipine appears to be tolerated better than the short-acting preparation in patients with this condition. The principal troublesome adverse effect during long-term therapy in these patients appears to be peripheral (ankle) edema.
Nifedipine has been used in selected patients to inhibit uterine contractions in preterm labor (tocolysis) and thus prolong gestation when such prolongation of intrauterine life was expected to benefit pregnancy outcome. Current ACOG guidelines for management of preterm labor state that there is no clear first-line tocolytic agent because of conflicting results regarding efficacy in comparative trials. In addition, concerns about the safety of short-acting (conventional) nifedipine (e.g., risks of serious hypotension and associated cardiovascular consequences) have prompted the manufacturers to warn against use of this preparation in conditions for which safety and efficacy have not been fully established.
(See Cautions.)However, an analysis of pooled data from a number of randomized, controlled studies suggests that calcium-channel blockers (principally nifedipine) may be more effective than, and preferable to, other agents (e.g., magnesium sulfate, β-adrenergic agonists) when tocolysis is deemed necessary. Results of this pooled analysis suggest that calcium-channel blockers are more effective in reducing births within 7 days of initiation of tocolytic treatment and before 34 weeks' gestation and are associated with improved neonatal outcomes (e.g., less neonatal respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, jaundice) and a reduced frequency of maternal adverse effects leading to treatment discontinuance compared with other tocolytic agents. A number of different dosages and dosage forms of nifedipine were used in these studies, and an optimal dosage regimen for the drug as a tocolytic has not been determined.
The main benefit currently derived from tocolytic therapy may be to forestall labor and provide time for patients to receive corticosteroids to increase fetal lung maturation and/or to be transferred to other (e.g., tertiary-care) facilities; any other potential benefits of prolonging pregnancy are unclear. For additional information, see Uses: Preterm Labor in
Acute Myocardial Infarction
Calcium-channel blocking agents have been used in the early treatment and secondary prevention of acute myocardial infarction (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).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.
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 the 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 short-acting (conventional, immediate-release) nifedipine is generally contraindicated in patients with MI because of its negative inotropic effects and the reflex sympathetic activation, tachycardia, and hypotension associated with its use. Short-acting nifedipine may be particularly detrimental in patients with hypotension and/or tachycardia since the drug may induce a reduction in coronary perfusion pressure, disproportionate dilatation of coronary arteries adjacent to ischemic areas (''steal'' phenomenon), and/or reflex activation of the sympathetic nervous system, resulting in an increase in myocardial oxygen demands. These findings are based on numerous clinical trials, including the Nifedipine Angina Myocardial Infarction Trial (NAMIS), the Trial of Early Nifedipine Treatment in Acute Myocardial Infarction (TRENT), the Norwegian Nifedipine Multicenter Trial, and the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT).