Nifedipine is a dihydropyridine calcium channel antagonist with predominantly vasodilatory activity. Modified-release formulations of nifedipine are effective antihypertensive and antianginal therapies and are generally well tolerated. Among the available formulations, those that produce a gradual increase in plasma nifedipine concentration, which is then sustained over a 24-hour period, are preferred, as they cause a gradual onset of vasodilatation and avoid baroreflex sympathetic activation (for example, nifedipine gastrointestinal therapeutic system [GITS] and a Japanese controlled-release formulation). Modified-release nifedipine had beneficial effects on a number of markers of vascular function, and nifedipine GITS reduced the need for coronary procedures in patients with coronary artery disease. In patients with hypertension, nifedipine GITS and nifedipine retard had beneficial effects on the overall incidence of major cardiovascular events, as did nifedipine retard in patients with concurrent hypertension and coronary artery disease.

Modified-release nifedipine: a review of the use of modified-release formulations in the treatment of hypertension and angina pectoris.

Given the major role of elevated blood pressure in the pathogenesis of both stroke and coronary heart disease, one of the biggest challenges facing public health authorities and medical practitioners is the control of hypertension worldwide, both in individual patients and at the population level. The prevalence of hypertension increases with age and is nearly 60% in people aged 65 - 74 years. With increasing age, polymorbidity and polypharmacy usually contribute to an increasingly complex approach to manage the respective clinical conditions, including the treatment of hypertension. All subgroups of calcium channel blockers are effective and well-tolerated in lowering blood pressure. They are of demonstrated benefit for the prevention of stroke in elderly patients with systolic hypertension. Calcium channel blockers are particularly recommended for elderly patients with systolic hypertension and for black patients. The nifedipine gastrointestinal therapeutic system (GITS) formulation provides a once-daily dosing regimen with a continuous and slow release of the drug, resulting in a smooth plasma concentration/time profile. The INSIGHT study established that nifedipine GITS decreased mortality and morbidity at the same level as standard diuretic treatment in hypertensive patients with additional risk factors. A subgroup analysis showed that the long-term protective effects of nifedipine GITS extended to hypertensive patients with diabetes mellitus and with previous myocardial infarction. Two substudies of INSIGHT showed that nifedipine slowed the progression of atherosclerosis in carotid arteries (intima-media thickness) and coronary arteries (coronary calcium) as compared to diuretic.

Clinical use of nifedipine GITS in the treatment of hypertension: an overview.

Objectives and background We previously reported that nifedipine retard showed comparable efficacy to angiotensin-converting enzyme (ACE) inhibitors for the prevention of cardiac events in hypertensive patients with coronary artery disease during the Japan Multicenter Investigation for Cardiovascular Diseases B study. In the nifedipine group, patients with a history of myocardial infarction (MI) showed a significant reduction in hospitalization for angina pectoris compared with the ACE inhibitor group. We investigated whether this difference was related to the progression of coronary arteriosclerosis. Methods To evaluate coronary arteriosclerosis, we performed coronary angiography (CAG) and a quantitative analysis of coronary angiograms. Results The cumulative incidence of hospitalization for angina was significantly lower in the nifedipine group (log-rank test P = 0.013). The etiology of angina requiring hospitalization was determined on the basis of CAG findings. Its incidence secondary to the development of new lesions or the progression of existing lesions was significantly lower in the nifedipine group than in the ACE inhibitor group (log-rank test P = 0.042 and P = 0.028, respectively). Using quantitative coronary analysis, changes in the coronary artery luminal diameter were compared between the nifedipine and ACE inhibitor groups. The minimum coronary lumen diameter did not show a significant change in the nifedipine group, whereas it decreased significantly in the ACE inhibitor group (paired t-test P = 0.002), and there was a significant difference between the two groups by analysis of covariance (P = 0.047). Conclusion These results indicate that nifedipine more effectively prevented admission for angina pectoris by inhibiting the progression of coronary artery disease in patients with a history of MI.

Nifedipine retard prevents hospitalization for angina pectoris better than angiotensin-converting enzyme inhibitors in hypertensive Japanese patients with previous myocardial infarction (JMIC-B substudy).

Introduction: Controlled clinical studies have clearly established the advantages of blood pressure (BP) reduction. However, optimal control of BP in the population is still not adequate. Monotherapy is ineffective in the majority of hypertensive patients, and multidrug therapy increases costs. Objective: The objective of the study was to assess to what extent and how uniformly BP can be controlled with two different 24-hour drug-releasing formulations of nifedipine, used as monotherapy. Methods: One hundred ninety-two patients of both genders, aged 18 to 65 years, with mild to moderate (Stage 1 and 2) essential hypertension with systolic BP 1.4 and T/P ratios of >0.5 was similar in both groups. An important correlation was found between the SI and T/P values. The incidence of adverse effects was low and similar in both groups. Conclusions: Target BP was reached in more than 70% of patients receiving monotherapy with either formulation. Both formulations were tolerated well.

A double-blind, controlled, multicenter, randomized study comparing the antihypertensive effectiveness and tolerance of a daily dose of two nifedipine formulations: nifedipine microgranules versus nifedipine osmotic pump.

Post-myocardial infarction (Ml) patients have a higher risk for subsequent cardiovascular and cerebrovascular events than the average population. This study was to test the effects on outcomes of nifedipine GITS compared to the diuretic combination co-amilozide in hypertensive patients with a history of Ml on outcomes (subset of the INSIGHT study). The multinational, randomised, double-blind International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study compared the treatment effects of nifedipine GITS 30 mg and co-amilozide (hydrochlorothiazide 25 mg plus amiloride 2.5 mg) in hypertensive patients aged 55-80 years with a blood pressure of 150/95 mmHg (or 160 mmHg systolic). This pre-specified subanalysis was performed in patients with a history of Ml. The primary outcome was a composite of cardiovascular death, non-fatal stroke, Ml, and heart failure. Of 6,321 randomised patients, 383 (6.1%) had a previous Ml. The percentage of primary outcomes in post-MI patients did not differ between the two treatment groups (14.9%). The number of post-MI patients with composite secondary outcomes was 53 (27.2%) in the nifedipine GITS group and 60 (31.9%) in the co-amilozide group. The incidence rates of primary and secondary outcomes were higher in patients with a previous Ml than in patients without a history of Ml. For the randomised use of nifedipine GITS and co-amilozide in hypertensive patients with a previous Ml, the choice seemed unimportant for outcomes and blood pressure lowering. The results of this subgroup analysis are consistent with INSIGHT's overall findings of no significant differences in efficacy, suggesting that post-MI hypertensive patients are no more likely to suffer further events when treated with long-acting nifedipine than on co-amilozide.

Alain Castaigne

Papers

The effect of nifedipine GITS on outcomes in patients with previous myocardial infarction: A subgroup analysis of the INSIGHT study