Uses
-
Hypertension
Amlodipine is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Amlodipine in fixed combination with atorvastatin (Caduet) is used in patients for whom treatment with both amlodipine and atorvastatin is appropriate.
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); data from clinical outcome trials indicate that lowering blood pressure with any of these drug classes can reduce the complications of hypertension and provide similar cardiovascular protection. However, recommendations for initial drug selection and use in specific patient populations may vary across these expert guidelines. 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.
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.
-
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 require 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 mmHg 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), 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 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
In current hypertension management guidelines, calcium-channel blockers are recommended as one of several preferred drugs for the initial treatment of hypertension; other options include 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 a 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).
(See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses.) 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. (See Geriatric Age under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses , and alsosee Ischemic Heart Disease under Hypertension: Antihypertensive Therapy for Patients with Underlying Cardiovascular or Other Risk Factors, in Uses .)
-
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). In patients who fail to respond adequately to initial monotherapy with a calcium-channel blocker, the JNC 8 expert panel states that an ACE inhibitor, an angiotensin II receptor antagonist, or a thiazide diuretic may be added. If goal blood pressure is not achieved with optimal dosages of these 2 drugs, a third antihypertensive agent from one of the recommended drug classes may be added; if more than 3 drugs are required, other antihypertensive agents (e.g., β-blockers, aldosterone antagonists, centrally acting agents) may be considered. Combined use of an ACE inhibitor and angiotensin II receptor antagonist should be avoided because of the potential risk of adverse renal effects. If the blood pressure goal cannot be achieved using the above recommended strategies, consultation with a hypertension specialist should be considered.
-
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. Many experts recommend the use of ACE inhibitors (or angiotensin II receptor antagonists) and/or β-blockers in hypertensive patients with stable ischemic heart disease because of the cardioprotective benefits of these drugs; all patients who have survived a myocardial infarction should be treated with a β-blocker because of the demonstrated mortality benefit of these agents. Other antihypertensive drugs such as calcium-channel blockers or thiazide diuretics may be added to the regimen as necessary to achieve blood pressure goals.
-
Diabetes Mellitus
Calcium-channel blockers, thiazide diuretics, ACE inhibitors, and angiotensin II receptor antagonists have all been recommended for use as initial antihypertensive therapy in patients with diabetes mellitus, although certain agents may be preferred. Some experts and clinicians have suggested that extended-release or intermediate- or long-acting calcium-channel blockers may be useful in the management of hypertension in patients with diabetes mellitus because these drugs appear to have few adverse effects on glucose homeostasis, lipid profiles, and renal function. The American Diabetes Association (ADA) states that the antihypertensive regimen of patients with diabetes and hypertension should include an ACE inhibitor or angiotensin II receptor antagonist because of the cardiovascular and renoprotective benefits of these drugs; if additional blood pressure control is required, a calcium-channel blocker or thiazide diuretic may be added. Because ACE inhibitors and angiotensin II receptor antagonists tend not to be as effective in black patients, some experts recommend a calcium-channel blocker or a thiazide diuretic as the initial antihypertensive drug of choice in black patients with diabetes.
(See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses.)
-
-
Other Special Considerations for Antihypertensive Therapy
-
Race
Blood pressure response to calcium-channel blockers appears to be comparable in white and black patients. In general, black hypertensive patients tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to monotherapy with other drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers). In a prespecified subgroup analysis of the ALLHAT study, a calcium-channel blocker was more effective than an ACE inhibitor in lowering blood pressure and was associated with a substantially reduced rate of stroke in black patients. When compared with a thiazide diuretic, the calcium-channel blocker appeared to be less effective in preventing heart failure, but comparable with respect to other outcomes (e.g., cerebrovascular, cardiovascular, renal, mortality). However, the diminished response observed with these other antihypertensive drug classes is largely eliminated when β-blockers are administered concomitantly with a diuretic or when ACE inhibitors or angiotensin II receptor antagonists are administered concomitantly with a calcium-channel blocker or thiazide diuretic. In addition, some experts state that when use of ACE inhibitors, angiotensin II receptor antagonists, or β-blockers is indicated in hypertensive patients with underlying cardiovascular or other risk factors, these indications should be applied equally to black hypertensive patients.
-
Geriatric Age
Antihypertensive drugs recommended for initial therapy in geriatric patients, including those with isolated systolic hypertension, generally are the same as those recommended for younger patients. Antihypertensive therapy initiated with a calcium-channel blocking agent has been shown to reduce cardiovascular morbidity and mortality in older patients with isolated systolic hypertension. In several controlled studies, thiazide diuretics alone or in combination with other antihypertensive agents also have been shown to effectively reduce morbidity and mortality in patients 50 years of age or older, including those with isolated systolic hypertension. Although some experts state that calcium-channel blocking agents or diuretics may be preferred in geriatric patients, ACE inhibitors and angiotensin II receptor antagonists also have shown beneficial effects and may be considered in this population.
For further information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults, in the Thiazides General Statement 40:28.20.
-
-
Hypertensive Crises
Because of the slow onset of hypotensive effect with amlodipine, this drug is not suitable for use as acute therapy in rapidly reducing blood pressure in patients with severe hypertension in whom reduction of blood pressure is considered urgent (i.e., hypertensive urgencies) nor in hypertensive emergencies.
For additional information on the role of dihydropyridine calcium-channel blocking agents in the management of hypertension and angina, .
-
-
Coronary Artery Disease
Amlodipine in fixed combination with atorvastatin (Caduet) is used in patients for whom treatment with both amlodipine and atorvastatin is appropriate.
-
Angina
Amlodipine is used for the management of Prinzmetal variant angina and chronic stable angina pectoris. The drug has been used alone or in combination with other antianginal agents.
-
Angiographically Documented Coronary Artery Disease
Amlodipine is used in patients with recently documented coronary artery disease by angiography (without heart failure or an ejection fraction less than 40%), to reduce the risk of coronary revascularization procedure and hospitalization due to angina.
-