James F. Burris

A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure in hypertensive patients.

Amlodipine is a new long-acting calcium antagonist that has a long half-life and appears to be suitable for once-daily administration. A double-blind, randomized, parallel, placebo-controlled study was conducted to evaluate the effect of amlodipine on ambulatory blood pressures in hypertensive patients. The study consisted of a 4-week single-blind placebo run-in phase, followed by 4 weeks of double-blind therapy. Ambulatory blood pressure was measured for 24 h at the end of the placebo run-in phase and after double-blind therapy. Sixteen patients were randomized to receive either amlodipine 5 mg or placebo in a 2:1 ratio. Amlodipine 5 mg daily significantly reduced supine and standing blood pressure 24 h postdose. Ambulatory blood pressure recordings revealed adequate blood pressure control throughout the 24-h dosing interval. Amlodipine was well tolerated and only two patients reported side effects--neither was withdrawn from therapy. No treatment-related abnormalities were noted. It was concluded that amlodipine 5 mg daily was effective antihypertensive therapy throughout the 24-h dosing period in the patients studied, and it was well tolerated.

First‐Line Therapy Option with Low‐Dose Bisoprolol Fumarate and Low‐Dose Hydrochlorothiazide in Patients with Stage I and Stage II Systemic Hypertension

This 30‐center, randomized, double‐blind, placebo‐controlled, parallel‐group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety advantage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure (−15.8 mm Hg/−12.6 mm Hg) than bisoprolol 5 mg alone (−10.0 mm Hg/−10.5 mm Hg) and HCTZ 25 mg alone (−10.2 mm Hg/−8.5 mm Hg). A 73% response rate was achieved with the low‐dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Antihypertensive effects were maintained during the 24‐hour dosing interval. The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety advantages over H25, as shown by less hypokalemia (<1% with B5/H6.25 versus 6.5% with H25). Treatment effects on triglycerides were similar to placebo, although small decreases in high‐density lipoprotein (HDL) cholesterol were observed in the bisoprolol‐treated groups. The benefits of low‐dose bisoprolol 5 mg/HCTZ 6.25 mg provide a rational basis for the use of this medication in the first‐line treatment of patients with stage I and stage II systemic hypertension.

Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension.

In the final analysis of this study at Week 26, 26% of the patients randomized to receive amlodipine attained blood pressure control with amlodipine alone compared with 33% of the patients allocated to hydrochlorothiazide (HCTZ). Neither amlodipine nor HCTZ produced clinically significant changes in pulse rate or in the electrocardiogram. Amlodipine treatment did not appear to produce clinically significant changes in blood lipids; HCTZ, however, produced an increase in total plasma cholesterol (delta 22.9 +/- 8.6 mg/dl). The incidence of side effects and the rate of patient withdrawal in the amlodipine and HCTZ groups were comparable. As expected, HCTZ therapy caused well-recognized biochemical alterations in cholesterol and potassium levels, whereas amlodipine was metabolically neutral.

The effect of amlodipine on ambulatory blood pressure in hypertensive patients

Certain high-risk populations, such as diabetics and blacks, have sustained elevation in blood pressure and heart rate throughout the day and night, with blunting of the usual diurnal variability pattern. This may contribute to their higher incidence of left ventricular hypertrophy (blacks) and cardiovascular complications (diabetics). Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives. Thus, to achieve maximum effectiveness in treating hypertension, 24-hour control of blood pressure is necessary. Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period. The objective of this study was to assess the effects of amlodipine, 5 mg once daily, on blood pressure measured by 24-hour ambulatory monitoring in a randomized, double-blind, placebo-controlled single-site study. Patients with mild-to-moderate essential hypertension were randomized to receive amlodipine (n = 11) or placebo (n = 5) in a 2:1 ratio. A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase. Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase. Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose (supine blood pressure -25.1/-10.1 mm Hg; standing blood pressure -21.2/-9.7 mm Hg) after 4 weeks of treatment. This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the antihypertensive effects of betaxolol to atenolol

A randomized double-blind multicenter study compared a new oral beta 1-adrenergic antagonist, betaxolol 10 to 40 mg (n = 71), with atenolol 25 to 100 mg (n = 75). Each drug was administered once daily for 24 weeks in patients with mild to moderate hypertension. Blood pressure (BP) measurements were taken 24 hours after dosing. Each drug produced significant (p less than 0.01) reductions in mean supine diastolic BP. The mean decrease in supine diastolic BP with betaxolol was significantly greater at weeks 4, 6, 10 and 12 (p less than 0.05). Throughout the remainder of the trial (weeks 14 to 24), no significant differences in BP reduction were noted between treatment groups. Normotension (supine diastolic BP less than or equal to 90 mm Hg) was achieved in 72% of those given betaxolol compared with 52% of those given atenolol (p less than 0.05). The most common side effects noted were bradycardia, fatigue and headache. The incidence of these and of central nervous system side effects was similar between the betaxolol and atenolol groups. Both agents were well tolerated. At recommended doses, betaxolol once daily may be more effective than atenolol once daily in patients with mild to moderate hypertension.

Strategic plan for geriatrics and extended care in the veterans health administration: background, plan, and progress to date.

The leaders of Geriatrics and Extended Care (GEC) in the Veterans Health Administration (VHA) undertook a strategic planning process that led to approval in 2009 of a multidisciplinary, evidence‐guided strategic plan. This article reviews the four goals contained in that plan and describes VHAs progress in addressing them. The goals included transforming the healthcare system to a veteran‐centric approach, achieving universal access to a panel of services, ensuring that the Veterans Affairs (VA) healthcare workforce was adequately prepared to manage the needs of the growing elderly veteran population, and integrating continuous improvement into all care enhancements. There has been substantial progress in addressing all four goals. All VHA health care has undergone an extensive transformation to patient‐centered care, has enriched the services it can offer caregivers of dependent veterans, and has instituted models to better integrate VA and non‐VA cares and services. A range of successful models of geriatric care described in the professional literature has been adapted to VA environments to gauge suitability for broader implementation. An executive‐level task force developed a three‐pronged approach for enhancing the VAs geriatric workforce. The VHAs performance measurement approaches increasingly include incentives to enhance the quality of management of vulnerable elderly adults in primary care. The GEC strategic plan was intended to serve as a road map for keeping VHA aligned with an ambitious but important long‐term vision for GEC services. Although no discrete set of resources was appropriated for fulfillment of the plans recommendations, this initial report reflects substantial progress in addressing most of its goals.

Effect of amlodipine on 24-hour ambulatory blood pressure in hypertensive patients.

Sixteen hypertensive patients (diastolic blood pressure of 95-114 mm Hg) were randomized to receive 5 mg of amlodipine daily or placebo, double blind, for 4 weeks. Antihypertensive efficacy was assessed using ambulatory blood pressure monitoring at baseline and following double-blind therapy in conjunction with sphygmomanometric measurement at 2-week intervals. Laboratory tests, ECG, and adverse effects were recorded to assess tolerability. Amlodipine treatment significantly reduced ambulatory blood pressure without altering the normal circadian variation throughout the monitoring period. Supine and standing blood pressure were significantly reduced by amlodipine 24 h postdose. Amlodipine was well tolerated and was not associated with reflex tachycardia.

Practical considerations in treating the elderly hypertensive patient

More than half of all older Americans die of cardiovascular diseases. Hypertension is a major risk factor for cardiovascular diseases, and its prevalence increases with age. Older patients are both at higher risk for end-organ complications and less likely than younger ones to survive such complications as myocardial infarction and stroke. Clinical studies have shown that reduction of elevated blood pressure is beneficial in many older persons. Optimal selection of antihypertensive therapy requires consideration of the special characteristics of the elderly, who differ from their younger counterparts in physiology, response to therapy and frequency of concomitant illnesses and medications. Calcium antagonists are particularly effective in these patients; other agents are useful in selected situations. Drugs that are likely to cause central nervous system side effects or orthostatic hypotension generally should be avoided in this patient population. Therapy should begin with a low dose and be titrated upward slowly, thus avoiding excessive reduction of blood pressure and the development of orthostatic hypotension. Treatment should be altered as necessary to minimize side effects that may impair quality of life or lead to poor compliance.

How to Fix the Dangerous Lack of Clinical Pharmacology Education in the Medical Profession: The Generation of Core Entrustable Professional Activities in Clinical Pharmacology for Entering Residency.

The past decades have seen the exponential development of virtually every aspect of the practice of medicine. Included among these developments has been an exponential expansion in the number of available pharmaceuticals, and so the discipline of clinical pharmacology must assure that education of medical students and training of medical residents increases concomitantly. This is an exciting time for theAmerican College of Clinical Pharmacology (ACCP) and other medically related societies. It is a time in which there is the opportunity to play a key role in reshaping the medical school curriculum to take advantage of all of the new information about pharmacogenomics, pharmacokinetics, pharmacometrics, and other parts of clinical therapeutics. Medical training must reflect the indispensable role of clinical pharmacology in the practice of medicine. During this critical time, we as well as others have noted a dangerous lack of clinical pharmacology education in current medical education curricula.1–4 Further, many contemporary clinical pharmacology educational articles advocate educational interventions designed to improve medical students’ perceptions of clinical pharmacology and improve prescription writing by providing small study group sessions.5 Although laudable, this approach is no substitute for providing succinct analytical reviews of each key concept, such as basic pharmacokinetic and pharmacodynamic principles, dosing adjustments, and complication resulting from lack of adherence. We propose that it is more effective to focus on educational interventions that mimic real-world prescribing competency than to rely on students’ self-assessments of competency as an endpoint. To quote Walter Kraft, MD, Associate Professor, Thomas Jefferson University School of Medicine, and Director, Clinical Research Unit, “At the end of the day the measure should be the ability of new residents to recognize and make higher-order decisions around proper drug dosing.” Therapeutic interventions in all medical subspecialties are complex due to unforeseen toxicities, drugdrug and drug-food interactions, dosing in special patient populations, and the increasing use of biological therapeutics. Medical professionals are also asked to operate in compliancewith institutional evidence-based guidelines, which may be restrictive and/or too vague to provide guidance in cases that do not fit the description

The effect of ramipril on ambulatory blood pressure: a multicenter trial.

The antihypertensive efficacy of ramipril was evaluated using 24-h noninvasive ambulatory sphygmomanometry in this double-blind, placebo-controlled study. One hundred subjects with mild-to-moderate essential hypertension were randomized to ramipril, 10 mg or placebo once daily for a 4-week treatment period. Ramipril decreased systolic and diastolic blood pressures throughout the 24-h period after dosing. Blood pressures measured manually 24 h postdose also showed that ramipril significantly reduced supine and standing blood pressures when compared with placebo. Incidences of adverse events were similar in the two study groups. Ramipril proved to be a well-tolerated agent with a sustained 24-h antihypertensive effect in this study.