The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation (ER) (E/D) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension. The trial design was a multicenter, randomized, double blind, placebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly assigned to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, enalapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 ± 2 h postdose) sitting blood pressure measurements at week 12 and at the end of the open label part of the study. Safety was evaluated based on patient symptoms, clinical laboratories, and electrocardiograms (ECG).

Blood pressure is a cardiovascular measurement with dynamic characteristics that can be influenced by a number of internal and external factors. The preferred blood pressure determination method would be one that reduces variability between measurements and that reflects the true blood pressure level. In this article, we present the variability of, and agreement between, the blood pressures collected by two indirect methods on the same patients during a hypertensive research project. Data obtained on patients in a typical clinical setting are also provided. Twenty-four-hour diastolic pressures obtained by the automated method demonstrated no regression to a lower mean, while blood pressures obtained casually in the office exhibited such regression. The 95% confidence interval of repeated measures for casual office blood pressure on a patient in a research setting (35/17 mm Hg) or in typical clinic practice (26/19 mm Hg) were similar, while the range of the mean 24-hour automated blood pressure monitoring (21/11 mm Hg) was smaller and demonstrated less variability. The magnitudes of the differences in blood pressures obtained on separate occasions in the same subjects were significantly lower with automated vs casual blood pressure determination methods (7.9/4.6 vs 13.7/7.4 mm Hg for both systolic and diastolic pressures). The agreement (95% confidence interval) between blood pressures obtained by the two methods (19/12 mm Hg) was found to be similar to the repeatability of automated blood pressure monitoring alone, and superior to that for data recorded casually in the office (35/17 mm Hg). Thus, the variability in mean 24-hour automated blood pressures is less than that for casual office blood pressures. The clinician should understand that the variability of blood pressures measured on an individual may be much greater than that reported for populations of hypertensive patients, and must be considered when applying epidemiologic group data to a specific patient. Moreover, any methodology of indirect blood pressure measurement that may reduce the variability and improve repeatability of casual office blood pressures deserves further consideration.

BACKGROUND The repeatability of 24-hour automatic ambulatory blood pressure measurements recorded by noninvasive equipment (Del Mar Pressurometer IV) was assessed to determine the intrapatient variability of this test. METHODS The usual antihypertensive medications of 73 patients with documented essential hypertension (supine diastolic blood pressure of 95 to 119 mm Hg) were withdrawn, and the patients were treated with placebo medication for 6 weeks. At the end of the placebo period, ambulatory blood pressure measurements of each patient were recorded every 15 minutes for 24 hours on two separate occasions 1 week apart. RESULTS There was no significant difference in either the 24-hour systolic or diastolic blood pressure for the entire group between weeks. A mean difference for individual patients between the first and second recording within 5 mm Hg was observed in 49.3% and 52.1% of patients for 24-hour systolic and diastolic blood pressure, respectively. The correlation coefficient for 24-hour systolic blood pressure was greater than 24-hour diastolic blood pressure (r = .87 vs r = .67). A difference greater than 18.1/14.9 mm Hg for systolic/diastolic blood pressure would be required to assign a significant (P less than .05) change in blood pressure between two recordings in the same patient. CONCLUSIONS These data quantify the usefulness of 24-hour ambulatory blood pressure measurements for a group of subjects. However, mean 24-hour ambulatory blood pressure varies significantly for individuals. Intrapatient variability may limit the usefulness of a single 24-hour ambulatory recording for an individual patient and suggests the need for more than one measurement to establish a level of blood pressure.

Data from 2 separate multicenter, double-blind clinical studies following the same protocol, except for the selection of doses, were pooled to evaluate the efficacy and tolerability of fixed doses of a new sustained-release (SR) formulation of nifedipine compared with placebo in 388 patients wtth mild to moderate uncomplicated essential hypertension. After a 3–6 week placebo washout period, the patients were randomized to receive either placebo or nifedipine SR-20 mg (study I only), 50 mg, 100 mg, or 150 mg (study II only). Among the 278 patients who completed 6 weeks of active therapy, mean supine diastolic blood pressure reductions from pretreatment baseline were 5.9,9.3,9.2,111, and 13.2 mm Hg hi the placebo, 20-, 50-, 100-, and 150-mg groups, respectively. The reductions achieved in each of the nifedipine SR groups were statistically significant versus baseline values (p <0.001). All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo (p <0.001). In addition, there was a significant linear relationship between the log of the dose and the blood pressure reduction (p <0.05). Automated ambulatory blood pressure recordings performed in 221 of the patients showed that the blood pressure was lowered evenly through the entire 24-hour dosing period. The doses that were effective and associated with the fewest adverse reactions were 20 mg and 50 mg once daily.

The evaluation and management of hypertension is based on indirect blood pressures obtained in the office (COBPs) using the mercury sphygmomanometer. The usefulness of COBPs is limited by factors such as observer bias, which confound the ability to discern the true blood pressure value. Automated portable monitors have been marketed, which also measure blood pressure (ABP) indirectly throughout 24 hours, but without human intervention. Acceptance of a new device that indirectly records blood pressure depends largely on its the agreement with the established method of blood pressure measurement. This review compares the variability of blood pressures collected indirectly by standard mercury sphygmomanometer and by an auscultatory automated portable blood pressure monitor. The results indicate that blood pressure, when measured indirectly in a hypertensive patient, is quite variable. Automated blood pressures were lower and demonstrated less within‐subject variability during repeated measures than COBPs. The agreement between ABPs and COBPs was better than the agreement between COBPs alone on successive visits. In addition, the mean hourly blood pressure profiles recorded throughout 24 hours by automated and manual methods from ten hypertensive patients were nearly identical. These data suggest that blood pressures measured by auscultatory automated methods are similar to and representative of those obtained manually.

Supine office blood pressures (SOBP) and 24-hour automated ambulatory blood pressure monitorings (AABPM) showed blood pressure reductions from a stable baseline to active treatment with 120-, 240-, and 480-mg doses of a new verapamil QD capsule (solid-spheroidal-oral once-daily drug-absorption system; (SODAS) in patients with mild-to-moderately severe (diastolic blood pressures 95-119 mm Hg) essential hypertension. Reductions were documented at 24 hours, hourly, and by the 24 hour average, using SOBP and AABPM, after the once-daily verapamil administration. Both SOBP and the 24-hour average by AABPM were significantly reduced from baseline by active verapamil treatment of 120-, 240-, and 480-mg doses. In comparison to verapamil QD (0 mg), blood pressure reductions from baseline to active treatment were significant at the 240- and 480-mg doses but not at the 120-mg dose. There was a significant linear dose response. This verapamil formulation (SODAS) was effective throughout the 24-hour period after once-daily dosing.