Peter B. Bottini

Magnetic resonance imaging compared to echocardiography to assess left ventricular mass in the hypertensive patient.

Echocardiography (ECHO) is useful to document changes in left ventricular mass (LVM) in groups of patients, but may be too variable for use in the individual patient. Magnetic resonance imaging (MRI) may be a more precise and reliable method to quantify the mass of the left ventricule. This study reports the accuracy, precision, and reliability of LVM estimates by MRI as compared to data obtained by ECHO in hypertensive patients. Accuracy referred to the comparison of LVM by MRI to anatomical LVM determined by autopsy. Precision was examined using 34 duplicate MRI images and by blindly reading 24 duplicate M-mode strips. Reliability was assessed by MRI in four subjects over 2 months, and by ECHO in 22 hypertensive patients over 2 weeks. Agreement between MRI and ECHO estimates of LVM was determined in the same 17 hypertensive patients using linear regression. MRI LVM estimates were within 17.5 g (95% CI) of the true LVM. The linear agreement between MRI and ECHO estimates of LVM could be described by the equation MRI = 0.61 x ECHO + 49.57 (r = 0.63, P < .01). The precision of LVM by MRI (11 g) was over twice that observed with ECHO (26 g). The reliability of MRI LVM estimates was more consistent (+/- 8 g) than that for ECHO (+/- 49 g). MRI appears to be a more precise and reliable method for measuring LVM, and would be more suitable than ECHO for the clinical evaluation of the individual patient.

Verapamil and nifedipine in combination for the treatment of hypertension.

The authors examined the efficacy and safety of the combination of verapamil and nifedipine in the control of hypertension. Retrospective analysis of blood pressures was obtained on 50 patients who had historically documented essential hypertension and were receiving verapamil and nifedipine. The patients had moderate to severe hypertension; 27 of 50 (54%) were uncontrolled on prescribed regimens of two or more separate classes of drugs. Control was defined by the ability to maintain a blood pressure of ≤ 160/90 by providing doses of verapamil (max: 480 mg/day) and nifedipine (max: 180 mg/day). Twenty‐nine (50%) were black and 21 (42%) were white. Ages ranged from 16 to 84 years. Mean duration of therapy was 1–2 years. Only 3 of 50 (6%) were control failures after providing verapamil and nifedipine. Three of 50 (6%) were discontinued because of side effects — reversible hepatitis (2) and rash (1). There were no serious adverse events, i.e., CHF or arrhythmias. Manageable ankle edema was seen in 14 of 50 (28%) patients. Verapamil and nifedipine, a combination of a dihydropyridine and a non‐dihydropyridine calcium antagonist, was effective and safe in this group of patients with difficult‐to‐manage hypertension.

Ambulatory Blood Pressure Monitoring: Methodologic Issues

Blood pressure, like heart rate, is a changing physiologic variable. Like ambulatory electrocardiography, ambulatory blood pressure can be recorded intermittently throughout the day. Ambulatory blood

Once-daily verapamil in the treatment of mild-to-moderate hypertension : a double-blind placebo-controlled dose-ranging study

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.

Variability and Similarity of Manual Office and Automated Blood Pressures

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.

Effectiveness of once-daily monotherapy with a new nifedipine sustained release calcium antagonist

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 with 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, 11.1, and 13.2 mm Hg in 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 less than 0.001). All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo (p less than 0.001). In addition, there was a significant linear relationship between the log of the dose and the blood pressure reduction (p less than 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.

Clinical and pharmacokinetic evaluation of a sustained-release liquid theophylline preparation

Theolan Suspension is the first long-acting liquid theophylline dosage form. A crossover study comparing the pharmacokinetic and clinical response to Theolan Suspension (administered every 12 hours) with aminophylline solution (administered every 8 hours) in children younger than 12 years of age is reported. Twenty-seven patients completed the study: 17 children were aged 6 years or younger and five patients were 3 years or younger. All patients were withdrawn from bronchodilator therapy and then were titrated to clinically effective doses of study medication. There was an equivalent and significant reduction from baseline levels in the mean symptom score during administration of theophylline suspension (42%; p less than or equal to 0.001) and aminophylline solution (57%; p less than or equal to 0.001). Mean values for FEV1 (1.2 versus 1.3 L), FEV1/FVC (77% versus 79%), and reduction in acute metaproterenol use (24% versus 43%) in children receiving theophylline suspension and aminophylline solution revealed no differences between products. Adverse effects were reported more frequently for the aminophylline solution, possibly caused in part to its taste. Of children stating a taste preference, eight of 10 children chose the Theolan Suspension. The suspension demonstrated a lower peak theophylline blood level at a later time (11.6 micrograms/ml at 3 1/2 hours), compared to the solution (14.6 micrograms/ml at 1 1/2 hours; p less than or equal to 0.01). Indexes of theophylline fluctuation during the dosing interval indicated equivalent or reduced variability for the suspension. Relative bioavailability of theophylline suspension was 89% of that for the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Once-Daily Monotherapy of Hypertension with Nifedipine Sustained Release (20mg to 100mg)

SummaryA 2-centre double-blind randomised clinical study was conducted to evaluate the efficacy and tolerability of fixed doses of a new sustained release (SR) formulation of nifedipine compared with placebo in 207 patients with mild to moderate uncomplicated essential hypertension. After a 3- to 6-week placebo washout period, patients were randomised to receive either placebo, nifedipine SR 20mg, nifedipine SR 50mg or nifedipine SR 100mg. All doses were taken once daily in the morning without food. Among the 157 patients who completed 6 weeks of active therapy, the mean diastolic blood pressure reductions from baseline at 24 hours postdose were 5.3mm Hg, 9.3mm Hg, 9.7mm Hg and 11.1mm Hg in the placebo and nifedipine SR 20mg, 50mg and 100mg groups, respectively (p < 0.01). Nifedipine SR given in fixed doses once daily produced a relatively uniform antihypertensive effect throughout the 24-hour dosing interval, as determined by ambulatory blood pressure monitoring. All 3 dosages of nifedipine SR were generally well tolerated. A major finding of this study was the efficacy and safety of the once-daily 20mg dose.