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Biomedical subjects

W B White

Publications and source records attributed to W B White.

At least 55 records · Page 3Linked to original sources
PubMed1998

Chronotherapeutics for cardiovascular disease.

Chronotherapeutics, or delivery of a medication in concentrations that vary according to physiological need at different times during the dosage period, is a relatively new practice in clinical medicine. Epidemiological studies document that the incidence of many cardiovascular diseases, including myocardial infarction and stroke, varies predictably in time over 24 hours (the circadian period). Advanced diagnostic technologies using ambulatory monitoring of the blood pressure and electrocardiogram have also demonstrated that there is marked variability in the level of pressure in hypertensive patients and the degree of myocardial ischaemia in patients with coronary disease. These diagnostic techniques also allow us to study the effects of varying the timing of administration or delivery of a concentration of a drug on end-points such as changes in blood pressure, heart rate or intensity of angina. The first chronotherapeutic agent for hypertension and angina pectoris, controlled onset, extended release (COER-24) verapamil, has recently been developed and registered in the US, Brazil, Canada and Mexico. The theoretical advantage of this formulation is that delivery of the active drug, verapamil, has been tailored to the typical circadian rhythm of blood pressure and heart rate in patients with hypertension and angina to better cover the early morning hours when cardiovascular need appears to be the greatest. An outcome study (CONVINCE) that evaluates primary prevention of cardiovascular events with this chronotherapy versus standard of care therapy is under way in several countries in North and South America and Europe.

Cardiovascular Diseases↗
PubMed1997

Effects of controlled-onset extended-release verapamil on nocturnal blood pressure (dippers versus nondippers). COER-Verapamil Study Group.

Approximately 1 in 4 patients with systemic hypertension have a 24-hour blood pressure (BP) profile characterized by a blunted or absent nocturnal decline in pressure. We evaluated the effects of a chronotherapeutic delivery system of controlled-onset extended-release (COER) verapamil hydrochloride and placebo in 257 hypertensive patients according to their circadian BP pattern in an 8-week prospective, multicenter, randomized, and double-blind clinical trial. Patients were stratified into 193 dippers (>10% decline in BP during the period of 10 P.M. to 5 A.M. compared with the hours of 5 A.M. to 10 P.M.) and 64 nondippers (<10% decline in BP during nighttime). During daytime, placebo-subtracted BP was similarly decreased in dippers and nondippers by COER verapamil. During nighttime, the placebo increased nocturnal BP in dippers (baseline nocturnal BP, 133/78 mm Hg) by 3/3 +/- 2/2 mm Hg and reduced BP by -5/-3 +/- 2/2 mm Hg in nondippers (baseline nocturnal BP, 152/94 mm Hg) (p = NS between groups). After controlling for age, gender, ethnicity, and the regression to the mean observed on placebo for all doses, COER verapamil reduced nocturnal BP more in nondippers than dippers -5.8/-2.4 mm Hg, p <0.0001 for systolic BP and p = 0.09 for diastolic BP). Additionally, a significant dose-related reduction in systolic and diastolic nocturnal BP (r = 0.56, p <0.0001 for systolic BP and r = 0.62, p <0.0001 for diastolic BP) was observed with COER verapamil after controlling for baseline covariates. These data demonstrate that nocturnal BP is decreased by a greater extent in nondipper hypertensives than in dipper hypertensives following treatment with COER verapamil HCL.

Antihypertensive Agents↗
PubMed1997

Ambulatory blood pressure monitoring is a useful clinical tool in nephrology.

Hypertension is a key factor in the genesis and deterioration of many renal diseases and is also a risk factor for death in patients with end-stage renal disease. However, the standard methods of measurement are prone to variability, especially in patients undergoing dialysis. The technique of ambulatory blood pressure monitoring allows a better assessment of overall blood pressure levels and promises to assume a bigger role in the care of renal patients. Ambulatory blood pressure monitoring is widely used in hypertension trials, and the reports of several consensus meetings on the clinical uses of ambulatory blood pressure monitoring have been published. Two similar validation protocols now exist for ambulatory blood pressure monitors, and tables of population-based normal blood pressures for age and gender are available. The available evidence suggests that ambulatory blood pressure compared with blood pressure measured in the physician's office is better correlated to left ventricular mass in subjects with chronic renal disease. Furthermore, studies in subjects with chronic renal disease and those undergoing renal replacement therapy show that blood pressure control is suboptimal in many patients and that nocturnal blood pressure is generally higher than in control subjects. Further insights into overall blood pressure behavior in this population will certainly emerge in the future.

Blood Pressure↗
PubMed1997

Abrupt, severe hypertension associated with dissection of a renal artery during selective catheterization.

A 23-year-old woman with longstanding renovascular disease associated with intimal dysplasia presented with stage I-II hypertension 6 years following bilateral percutaneous renal artery angioplasties (associated with normotension after antihypertensive agents). Following the diagnostic selective left renal arteriogram, blood pressure (BP) rose from 140/90 mm Hg to 200/130 mm Hg over 30-40min. Reassessment angiography revealed a proximal intimal dissection with the development of a lengthy false lumen. Attempts to cross the dissected area for stent placement were unsuccessful. To avoid the consequences of severe and accelerated hypertension, intravenous enalaprilat was administered (which lowered BP to 160-170/100 mm Hg) and the patient underwent emergency aortorenal bypass surgery. Fortunately, the BP normalised post-operatively and renal function remained normal. This case illustrates the possibility that catheterisation of a renal artery may lead to acute, severe hypertension by creating an acutely ischaemic kidney through intimal or medial arterial dissection. In such cases, pharmacologic blockade with angiotensin-converting enzyme inhibitors may provide stabilisation of BP to allow surgical revascularisation to proceed safely.

Acute Disease↗
PubMed1997

Usefulness of moexipril and hydrochlorothiazide in moderately severe essential hypertension.

The purpose of this study was to assess the efficacy and tolerability of the angiotensin-converting enzyme inhibitor moexipril alone and in combination with hydrochlorothiazide versus hydrochlorothiazide monotherapy in patients with stage II and III essential hypertension. This was a double-blind, randomized, multicenter trial that evaluated moexipril (15 and 30 mg once daily), hydrochlorothiazide (25 and 50 mg once daily), and combinations of the drugs (15 mg moexipril/25 mg hydrochlorothiazide and 30 mg moexipril/50 mg hydrochlorothiazide) in 272 hypertensive patients whose seated diastolic blood pressure (BP) was 100 to 114 mm Hg. The primary efficacy variable was the mean change from baseline in seated diastolic BP at the end of the dosing period. Secondary efficacy measures included changes in systolic BP and standing BP. The lower doses of moexipril and hydrochlorothiazide reduced diastolic BP similarly (-8.0 +/- 1.4 versus -8.1 +/- 1.4 mm Hg; p = NS) as did higher doses of the monotherapeutic regimens (moexipril, -9.7 +/- 1.2 mm Hg versus hydrochlorothiazide, -11.0 +/- 1.2 mm Hg, p = NS). Combinations of moexipril and hydrochlorothiazide reduced diastolic BP significantly more than either monotherapy (lower doses, -16.0 +/- 1.4 mm Hg; p < 0.001; higher doses, -17.9 +/- 1.2 mm Hg; p < 0.001). Similar trends were observed for the systolic BP. Discontinuation rates due to adverse events were 0% for the moexipril monotherapy patients and 3% to 5% in patients on diuretic or combination treatment. These data demonstrate that 15 and 30 mg moexipril once daily lower BP similarly to hydrochlorothiazide in patients with stage II and III hypertension. There is also an additive effect when combining the two agents that lowers BP more significantly than either monotherapy.

Adult↗
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↗