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Endocrine and Renal Effects of Nifedipine Gastrointestinal Theraputic System in Patients With Essential Hypertension: Results of a Multicenter Trial - MATH
Description:
The MATH trial was an observational study to evaluate clinical efficacy, safety, and effects on metabolic parameters of a once daily nifedipine gastrointestinal therapeutic system (GITS) in hypertensive patients. Also, the MATH trial was designed to specifically analyze the subgroups of patients with diabetes and obesity for adverse effects of therapy on serum lipids and glucose measurements.
Hypothesis:
The nifedipine GITS formulation will be associated with reduced blood pressure in a broad range of hypertensive patients without adverse effects on renal and metabolic parameters.
Study Design
Study Design:
Patients Enrolled: 1,155
Mean Follow Up: 12 weeks
Mean Patient Age: 58 ± 11
Female: 25
Patient Populations:
Patients with mild to moderate hypertension
Exclusions:
Serious coexisting disease, isolated systolic hypertension, orthostatic hypotension, or gastrointestinal dysfunction
Primary Endpoints:
Change in blood pressure during the study period
Secondary Endpoints:
Change in serum concentrations of electrolytes, BUN, creatinine, lipids, and glucose; and adverse events
Drug/Procedures Used:
Patients were tapered over a 2-3-week period from any antihypertensive medications. Patients then entered a two-week placebo phase where baseline parameters including vital signs were measured.
Patients with an average sitting diastolic blood pressure from 95 to 110 mm Hg proceeded to a 1-6-week titration phase. Dosing with nifedipine GITS began at 30 mg per day and could be increased as required up to 180 mg per day until goal blood pressure was achieved.
Goal blood pressure was defined as a 10 mm Hg drop in sitting diastolic blood pressure and a sitting diastolic blood pressure less than 90 mm Hg. Patients who achieved goal blood pressure entered an efficacy phase where they were followed for 12 weeks.
Principal Findings:
A total of 1,155 patients were enrolled from 127 centers in the United States. Of these, 1,138 completed the titration phase and 868 responded to therapy. Of these, 761 completed the 12-week treatment period.
Of the initial 1,155 patients, 251 did not have baseline glucose levels and were excluded from the analysis. Of the 1,155 patients, 157 were diabetic (vast majority type II). There were 458 obese patients, 489 overweight patients, and 206 patients of normal weight.
Sitting blood pressure was reduced in both diabetic (159-138 mm Hg, p<0.001) and nondiabetic patients (152-135 mm Hg, p<0.001) compared to baseline. There was a significantly greater decrease in mean systolic and diastolic blood pressure in diabetic compared to nondiabetic patients (shown graphically on paper). The mean daily dose of nifedipine GITS was comparable for both diabetics and nondiabetics (80 ± 47 mg per day for diabetics and 81 ± 46 mg/day for nondiabetics). The percentage of patients achieving goal blood pressure at the end of the titration phase was 84% for diabetics and 78% for nondiabetics. Changes in sitting blood pressure did not vary with body mass index.
No significant differences occurred with serum lipid measurements over the course of the trial. There were also no clinically significant changes from baseline for serum sodium, potassium, calcium, chloride, blood urea nitrogen (BUN), or creatinine. For nondiabetics, there was a small but significant increase in plasma glucose (97-101 mg/dl, p<0.001). Uric acid levels significantly decreased in all subgroups (diabetic, nondiabetic, obese, and overweight) except normal weight patients.
The most common reported side effect was edema, which caused discontinuation of medication in 8.6% of patients. Impotence occurred in 1.9% of diabetic patients and 2.8% of nondiabetic patients.
Interpretation:
Nifedipine GITS was associated with significant reduction in blood pressure in a large cohort of patients including those with diabetes and obesity. Nifedipine GITS was not associated with adverse effects on serum lipids or glucose concentrations in obese and diabetic patients. Despite the promising blood pressure findings, the trial was nonrandomized and there was no comparison group.
References:
Tuck M, Bravo E, Krakoff L, Friedman CP. Endocrine and renal effects of nifedipine gastrointestinal therapeutic system in patients with essential hypertension. Results of a multicenter trial. The Modern Approach to the Treatment of Hypertension Study Group. Am J Hypertens 1990;3:333S-341S.
Keywords: Sodium, Lipids, Blood Urea Nitrogen, Edema, Creatinine, Nifedipine, Uric Acid, Calcium Channel Blockers, Glucose, Potassium, Body Mass Index, Erectile Dysfunction, Obesity, Hypertension, Diabetes Mellitus
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