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Biomedical subjects

W B White

Publications and source records attributed to W B White.

At least 19 recordsLinked to original sources
PubMed1996

Dose dependence of chronic positive inotropic effect of vesnarinone in patients with congestive heart failure due to idiopathic or ischemic cardiomyopathy.

Vesnarinone is a novel oral agent that improves survival and symptoms of patients with dilated cardiomyopathy. Although it is thought to have positive inotropic effects, clinical data supporting this mechanism in patients with severe heart failure remain scant. The present study tested whether 3 months of oral vesnarinone therapy increases the inotropic state and whether this response is dose dependent. Twenty-one patients with dilated cardiomyopathy (New York Heart Association class III to IV) were randomized to 30 mg/day (n = 11) or to 60 mg/day (n = 10) of vesnarinone. Cardiac function was assessed before and after therapy by radionuclide ventriculography to measure left ventricular volume and flow and by noninvasive measurement of the central aortic pressure wave. The inotropic effect of vesnarinone was assessed by a recently validated index equal to the ratio of left ventricular maximal ventricular power divided by the square of end-diastolic volume (PWRmax/ EDV2). This ratio is sensitive to inotropic change but is minimally altered by chamber loading. After 3 months of 60 mg/day therapy, PWRmax/EDV2 increased by 28 +/- 32%. Ejection fraction and cardiac output also increased by 21 +/- 14% and 14 +/- 14%, respectively, and arterial load decreased by 10.5 +/- 12.4% (all p < 0.005). End-systolic volume also declined by 7 +/- 10%, suggesting reverse remodeling. These changes were smaller and none achieved statistical significance at the 30 mg/day dose (e.g., 14.2 +/- 35.4% for PWRmax/ EDV2). Heart rate was unchanged with either dose. Thus, chronic vesnarinone treatment dose modestly raises the inotropic state and lowers afterload in patients with dilated cardiomyopathy in a dose-dependent fashion.

Administration, Oral↗
PubMed1996

Clinical outcome of a mandatory formulary switch for dihydropyridine calcium channel blocker therapy at a Veteran's Administration Medical Center.

Recently, changes in antihypertensive therapies with similar properties have been made based primarily on cost savings for hospital formularies. To assess blood pressure (BP) control and adverse side effects associated with a switch of patients on nifedipine GITS to felodipine at our Veteran's Administration Medical Center (VAMC), we prospectively studied physician records and patient-reported side effects (both from the medical record and patient questionnaires) in 127 hypertensive patients (70 +/- 10 years, 95% men, 88% nonblack, 44% with coronary disease) who underwent the forced switch in therapy. During the period of patient visits/chart review, physicians were unaware that the study was being conducted. A minimum of 2 months and two visits on each therapy was required for patient inclusion. The mean doses of nifedipine GITS and felodipine used were 55 +/- 24 mg/day and 8 +/- 2.6 mg/day, respectively. The use of supplemental antihypertensive agents was similar in both calcium channel blocker groups. Systolic BPs and heart rates were similar in patients taking the two drugs, and the diastolic BP was modestly lower in patients taking felodipine (78 +/- 10 mm Hg for felodipine and 80 +/- 10 mm Hg for nifedipine, P < .05). There were no differences in the incidence of side effects (both patient-reported and provider-reported) for the two antihypertensive therapies. These data demonstrate that in an hypertensive population followed in a VAMC, mandatory switching of stable dihydropyridine calcium channel blocker therapy did not result in any significant changes in short-term (2 to 3 months) BP control nor were adverse side effects different based on both physician- and patient- reported sources of information.

Aged↗
PubMed1996

A chronotherapeutic approach to the management of hypertension.

Patients with hypertension have a characteristic circadian pattern of blood pressure (BP) variability in a 24-h period, characterized by a wide range while awake and active, and a narrower range during sleep and inactivity. Blood pressure in the untreated hypertensive individual declines by approximately 10% to 20% during sleep compared with the mean awake BP values. Early in the morning (assuming a typical day-night activity cycle), the BP rises sharply on awakening, when physical and mental activities increase. Antihypertensive therapy has been traditionally dosed in the morning after awakening, and in recent years most of the newly developed antihypertensive agents have been once-daily, long-acting preparations. However, theoretically, this pattern of drug dosing may be suboptimal since pharmacodynamic activity is attenuated at the end of the dosing period, when a large rise in BP may occur. Presently, only a few studies have been performed to evaluate the effects of nocturnal dosing of standard long-acting drugs. Consequently, we undertook an assessment of the effects of a new formulation of verapamil--controlled onset extended release verapamil HCl (COER-24)--that is dosed nocturnally and has a controlled onset of delivery (4 to 5 h postdose) and an extended release for the remainder of the dosing period. Through ambulatory BP monitoring, evaluation revealed that this verapamil formulation produced changes in BP that followed the circadian rhythm of BP: lower reductions during sleep, when the BP is intrinsically lowest, and appropriately larger reductions during the early morning and daytime hours, when ambulatory BP values accelerate and plateau to their highest levels. These data demonstrate that it is possible to design antihypertensive therapy for once-nightly dosing, thereby providing a chronotherapeutic regimen for patients with hypertension.

Antihypertensive Agents↗
PubMed1996

"Inappropriate" physician habits in prescribing oral nifedipine capsules in hospitalized patients.

Despite the absence of an approved Food and Drug Administration (FDA) indication, the use of oral or "sublingual" nifedipine for hypertension in the hospitalized patient has become an increasingly common practice. The purpose of the study was to assess the clinical circumstances for which the drug was being prescribed and the practices of attending and resident physicians. Dosing of oral nifedipine capsules in medical and surgical inpatients was studied prospectively in three central Connecticut hospitals (University, community-teaching, and private nonteaching) during a 60-day period from January to March, 1994. Through evaluation of computerized pharmacy and medical records, data were collected on diagnostic reasons for ordering nifedipine, pre- and posttreatment blood pressures, dosing frequency, clinical documentation associated with drug prescription, and adverse events. Physicians and nurses at the respective hospitals were unaware of the conduct of the study. The incidence of nifedipine capsule administration at all three hospitals was 3.4% (152 dosings in 83 patients/4489 hospitalized patients/ 60 days). Practice habits and blood pressure changes differed minimally among hospitals and physicians. Sixty-three percent of nifedipine orders were given over the telephone for arbitrary and asymptomatic blood pressure elevations and 98% of the orders lacked bedside patient evaluation. Follow-up of the blood pressure was performed within 1 h in 51% of patients and within 2 h in 24%, while in 25% there was no documentation of follow-up until 2 to 6 h after nifedipine dosing. Mean pretreatment blood pressure was 186/94 +/- 20/16 mm Hg (range: 150 to 260 mm Hg systolic and 50 to 125 mm Hg diastolic). Blood pressure fell 32/16 +/- 22/16 mm Hg (range: -92 to +8 mm Hg systolic and -90 to +28 mm Hg diastolic) and was related to the level of pretreatment blood pressure (r = 0.53 for systolic blood pressure, and r = 0.49 for diastolic blood pressure, P < .001 for both). Large, asymptomatic blood pressure reductions were common. One hypertensive patient experienced severe hypotension accompanied by an anterior wall myocardial infarction. These data demonstrate inappropriate physician prescribing of oral nifedipine in hospitalized patients characterized by a lack of proper assessment prior to drug dosing, highly arbitrary treatment parameters that were written without regard for symptoms or underlying illnesses, and slow follow-up for evaluation of the clinical response to therapy.

Administration, Oral↗
PubMed1996

Relevance of the trough-to-peak ratio to the 24 h blood pressure load.

The ambulatory blood pressure load is generally defined as the proportion of elevated systolic or diastolic pressures over a 24 h period. This value represents the chronic pressure overload that induces myocardial and vascular damage associated with the hypertensive disease process. Blood pressure load has been defined as either the percentage of blood pressures exceeding 140/90 mm Hg while awake and 120/80 mm Hg during sleep or the integrated area under the blood pressure curve that exceeds the same values. Studies in untreated hypertensive patients have demonstrated that the blood pressure load is a better determinant of indices of hypertensive heart disease or hemodynamic indices than either the casual or mean ambulatory blood pressure. Thus, blood pressure load has become a popular method for the assessment of antihypertensive drug efficacy. Intuitively, drugs that have a low trough-to-peak ratio should be associated with an increased blood pressure load as the agent is losing its effectiveness at the end of the dosing period. However, the extent of the reduction at trough and peak times must be taken into consideration when evaluating these relationships. Some therapeutic modalities clearly have excessive blood pressure loads due to short therapeutic duration. Conversely, some agents with long durations of action may be associated with excessive blood pressure loads secondary to modest blood pressure reduction over time.

Antihypertensive Agents↗
PubMed1996

Determinants of the white-coat effect in hypertensive subjects.

To determine the magnitude and the relationships of the difference between office and awake ambulatory blood pressures (BP) (white-coat effect) in ambulatory hypertensive patients, 64 consecutive patients referred to the ambulatory BP monitoring laboratory were studied. All subjects were evaluated prospectively by study nurse, study doctor, and ambulatory BP measurements. Order of measurements was randomized and observers were blinded to each others readings. No differences were found in the white-coat effects among study nurse (22/14 +/- 20/9 mm Hg), study doctor (27/12 +/- 20/10 mm Hg) and referring doctor (19/11 +/- 18/10 mm Hg). Similarly, female and male patients exhibited similar white-coat effects on the day of ambulatory monitoring. Older patients (> or = 65 years) displayed higher mean systolic white-coat effects than younger patients (29 +/- 18 mm Hg vs 19 +/- 19 mm Hg, P = 0.04). Multivariate analysis using the mean average systolic white-coat effect as the dependent variable and age, gender, treatment status, body mass index (BMI) and duration of hypertension as independent variables showed a significant independent role for age. In contrast, no clinical correlates of the diastolic white-coat effect were found. Older patients are more likely to display a systolic white-coat effect in the medical care environment.

Age Factors↗
PubMed1995

Nocturnal dosing of a novel delivery system of verapamil for systemic hypertension. Verapamil Study Group.

To evaluate the efficacy and safety of a novel delivery system of physiologic pattern release (PPR)-verapamil administered nocturnally to patients with stages I and II hypertension using ambulatory blood pressure (BP) monitoring, we performed a multicenter (17 centers), double-blind, randomized, placebo-controlled, parallel-group trial with placebo and 120, 180, 360, and 540 mg of verapamil in 287 randomized patients. The delivery system has a delay in the release of verapamil for 4 to 6 hours, and then delivers the drug from an osmotic pumping system for approximately 12 hours. Patients were dosed at 10 P.M. The primary end point was change from baseline in trough diastolic BP assessed by ambulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, whereas secondary measures included changes from baseline in peak, early morning (6 to 10 A.M.) systolic and diastolic BP, trough clinic BP, and 24-hour average daytime (8 A.M. to 8 P.M.) and nighttime (8 P.M. to 8 A.M.) BP. The 180, 360, and 540 mg verapamil doses achieved statistically significant reductions in trough (6 to 10 P.M.) diastolic BP (-3.9 +/- 1.0, -7.8 +/- 1.2, and -10.6 +/- 1.1 mm Hg, respectively). Reductions in peak early morning (6 to 10 A.M.) diastolic BP were greater (-4.6 +/- 0.9, -13.3 +/- 1.2, and -19.0 +/- 1.2, for 180, 360, and 540 mg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.

To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 15-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P < .01 for the 15-mg dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of actual versus arbitrary awake and sleep times on analyses of 24-h blood pressure.

Investigators conducting hypertension trials with ambulatory blood pressure (BP) monitoring have been analyzing study results using arbitrary times for day (wakefulness) and night (sleep). We prospectively evaluated the impact of using arbitrary times instead of patient reported awake and sleep times on mean 24-h, awake, and sleep BP, BP loads, and the awake-sleep BP difference in 50 subjects. Daytimes and nighttimes were derived from popular, arbitrary times reported in the literature. Compared to actual awake and sleep periods, arbitrary day and night division caused no significant differences in the mean awake and sleep BPs. However, limits of agreement for BP values derived for the actual and arbitrary times of wakefulness and sleep were substantial especially during sleep (awake systolic BP, -4 to 7 mm Hg; awake diastolic BP, -2 to 4 mm Hg; sleep systolic BP, -12 to 7 mm Hg; and sleep diastolic BP -7 to 4 mm Hg). Sleep BP loads (proportion of BPs > 120/80 mm Hg) were altered by greater than 10% in 20% to 30% of the subjects, depending on choice of time schedule. These data demonstrate that the calculation of BP and BP load during sleep may be altered by use of arbitrary, rather than actual, times of wakefulness and sleep in 24-h studies of ambulatory BP.

Analysis of Variance↗
PubMed1995

Ambulatory blood pressure monitoring in current clinical practice and research.

As more scientific evidence accumulates concerning the relationship between ambulatory blood pressure and hypertensive organ disease, the technique of ambulatory blood pressure monitoring appears to be gaining a foothold in clinical practice and research. Over the past 2 years, an important follow-up study has revealed that 'white coat' hypertension has a low morbidity compared with sustained hypertension. However, other cross-sectional studies continue to fuel the debate regarding the definition and risks associated with white coat hypertension. The application of ambulatory blood pressure monitoring to clinical hypertension trials remains superior to that of office blood pressure measurements. As further data from other prospective interventional studies are published in the next few years, further definition of the utility of the technique will be possible.

Blood Pressure↗
PubMed1995

Normal-appearing captopril MAG-3 renal scintigraphy in hemodynamically significant renal artery stenosis. A case report.

The finding from a normal-appearing angiotensin converting enzyme (ACE)-inhibitor renal scan is generally reassuring to the physician screening for renovascular hypertension. In fact, the false-negative rate for captopril scintigraphy is very low. Possible reasons for false-negative scans have not been well documented. A fifty-two-year-old man was evaluated and found to have renovascular hypertension on two occasions, at initial presentation and again eight months later (restenosis had occurred). Renovascular hypertension was present on both occasions as judged by decline of blood pressure following angioplasty of right renal artery stenosis (approximately 80% and approximately 70% stenosis on the two occasions, respectively). However, ACE-inhibitor renal scanning with 99mTc MAG-3 gave disparate results on the two occasions. The first study using oral captopril (25 mg) indicated a low probability of renal artery stenosis, whereas the second study done with the patient regularly taking lisinopril (10 mg daily) was markedly positive. Possible reasons for the initial negative study include poor absorption of oral captopril or inadequate inhibition of the renin-angiotensin system by the 25 mg dose.

Captopril↗
PubMed1995

Ambulatory blood pressure monitoring in the evaluation of hypertension therapy.

During the past decade, ambulatory monitoring of the blood pressure has become an important tool for evaluating the pharmacodynamics and clinical efficacy of antihypertensive drugs during development. Furthermore, this methodology aids physicians in practice in the assessment of blood pressure control in many subsets of patients with hypertension.

Blood Pressure Monitoring, Ambulatory↗
PubMed1995

Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension.

The purpose of this study was to evaluate the long-term safety and efficacy of moexipril, a non-sulphydryl angiotensin converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in older patients with hypertension. One hundred and seventy two hypertensive men and women, 65-80 years old, with seated DBP between 95 and 114 mm Hg were studied. The study was a 2 year, multicentre (12 centres), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse effects and laboratory studies were assessed following moexipril at 7.5 or 15 mg once daily or 7.5 or 15 mg daily in combination with 25 mg of hydrochlorothiazide if the seated DBP remained > or = 90 mm Hg on moexipril monotherapy. The primary measure of efficacy was a change from baseline in seated DBP. Secondary outcome measures included changes in seated DBP, pulse rate, laboratory parameters and adverse side-effects. Following 1 year of therapy in 135 patients, the BP fell 16/14 mm Hg among patients receiving moexipril monotherapy and 27/17 mm Hg for those receiving combined therapy compared with baseline (P < 0.001 for both). After 2 years of treatment, reductions were similar in 120 patients. Nineteen patients (11%) were prematurely withdrawn from the study because of inadequate therapeutic response and 28 (16%) because of adverse experiences. There were no significant changes in pulse rate or postural reductions in BP on either moexipril monotherapy or combination treatment. Three adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril or combination therapy: hypotension (2%), dizziness (6%) and increased cough (12%). There were no clinically relevant mean group changes from baseline laboratory values in the treatment groups. In conclusion, these long-term data demonstrate that moexipril, either alone or in combination with hydrochlorothiazide, has long-term anti-hypertensive efficacy and is generally well tolerated in elderly patients with hypertension.

Aged↗
PubMed1994

Accelerated hypertension with encephalopathy due to an isolated dissection of a renal artery branch vessel.

Typical causes of renovascular hypertension include intramural atherosclerotic lesions of the main renal arteries or their branches and fibromuscular dysplasia of the renal arterial wall with luminal narrowing. We report a patient with new-onset, accelerated hypertension (blood pressure 220/140 mm Hg, status epilepticus, retinal hemorrhages) secondary to a dissection of the anterior division of the right renal artery that was accompanied by hyperreninemia, hyperaldosteronism, and hypokalemia. At presentation in the untreated state, unstimulated plasma renin activity and the serum aldosterone level were markedly elevated. Following right nephrectomy, blood pressure levels normalized without antihypertensive therapy, and plasma renin activity, serum aldosterone and potassium levels normalized. Histologic study of the right renal artery showed an isolated dissection of the anterior branch of the vessel between the muscularis and adventitia that created marked reduction in luminal diameter and renal ischemia. There was no evidence of any other vascular abnormalities, atherosclerosis, or fibromuscular dysplasia. These findings demonstrate that an isolated dissection of a branch of the renal artery may induce profound hyperreninemia and represents a rare, reversible etiology for accelerated hypertension associated with acute encephalopathy.

Adult↗