Nisoldipine is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.
Calcium-channel blocking agents (e.g., nisoldipine) 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 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.
Interim analysis (mean follow-up: 5 years) of a prospective, randomized, double-blind study (the Appropriate Blood Pressure Control in Diabetes; [ABCD trial]) in hypertensive patients with type 2 (noninsulin-dependent) diabetes mellitus (NIDDM) indicated that use of nisoldipine was associated with a fivefold higher risk of fatal and nonfatal myocardial infarction than enalapril. However, these findings of increased cardiovascular risk should be interpreted with caution, since they were based on analysis of secondary clinical end-points. The ABCD study originally was designed to compare the effects of moderate control of blood pressure (target diastolic pressure of 80-89 mm Hg) with those of intensive control of blood pressure (target diastolic pressure of 75 mm Hg) on the incidence and progression of complications of diabetes (i.e., renal function measured by the 24-hour creatinine clearance). Based on these findings, however, the trial's Data Safety and Monitoring Board recommended that the nisoldipine treatment arm be terminated prematurely (67 months after initiation of the study) and that such patients be switched to enalapril therapy. It is not known whether the higher incidence of myocardial infarction associated with the use of nisoldipine in this study resulted from a deleterious effect of the drug, a beneficial effect of enalapril, or a combination of these effects. It also should be considered that many patients receiving enalapril also were receiving β-blockers, drugs known to have a beneficial effect on myocardial infarction. In addition, findings from the robust ALLHAT study revealed no difference in the primary outcome of combined fatal coronary heart disease or nonfatal myocardial infarction among thiazide diuretics (chlorthalidone), calcium-channel blockers (amlodipine), and ACE inhibitors (lisinopril). (.)
For further information on overall principles and expert recommendations for treatment of hypertension, see For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, .
Because of the slow onset of hypotensive effect with extended-release nisoldipine tablets, this dosage form is not suitable for use as acute therapy in rapidly reducing blood pressure in patients with hypertensive crises, including those with severe hypertension in whom reduction of blood pressure is considered urgent (I.e., hypertensive urgencies) or an emergency (hypertensive emergencies).