PubMed Health⌕ Search

Biomedical subjects

W C Cushman

Publications and source records attributed to W C Cushman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension.

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). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, respectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure (-7.9 and -9.0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus placebo. E/D effectively lowered SiDBP and SiSBP during the open label extension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fatigue, cough, rash, and impotence. The event frequency for the combinations were similar to those seen with the monotherapies. Fixed combinations of E/D were generally well tolerated, with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension.

Adult↗
PubMed1998

The clinical significance of systolic hypertension.

Large-scale epidemiologic studies and clinical trials have contributed to an increased recognition of the importance of systolic hypertension. Data from landmark epidemiologic studies such as the Multiple Risk Factor Intervention Trial screenee follow-up and the Framingham Heart Study have demonstrated that elevated systolic blood pressure dramatically increases the risk of cardiovascular events. Of particular concern is the extremely high risk associated with isolated systolic hypertension (ISH), which is much more common in the elderly than in young adults. Clinical trials have identified significant risk reductions after treatment with diuretics or the dihydropyridine calcium antagonist nitrendipine in older individuals with ISH. Beta blockers have not been associated with such benefits. The recently released sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) recommends drug therapy for all patients with stage 1 (140 to 159 mm Hg) or stage 2-3 (> or = 160 mm Hg) systolic hypertension, whether it occurs in isolation or in conjunction with diastolic hypertension. The sixth JNC report identified diuretics as the initial therapy of choice, with a long-acting dihydropyridine calcium channel blocker as an alternative if diuretics are ineffective or not well tolerated. More research is needed to evaluate other classes of drugs in this setting. Regardless of the choice of therapy, patients should be encouraged to adopt lifestyle modifications such as weight loss, exercise, sodium restriction, and reduced alcohol consumption.

Antihypertensive Agents↗
PubMed1997

Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension.

The combination of angiotensin converting enzyme (ACE) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension. Previous study designs have often been inadequate to demonstrate the details of interactions between these antihypertensive agents. This study used a modified 4 x 4 factorial randomized, double-blind, placebo-controlled, parallel group design to study the efficacy of 17 different doses of fosinopril (Fos), a phosphinic acid derived ACE inhibitor, and hydrochlorothiazide (HCTZ) in 550 patients with mild to moderate hypertension. Data from these variables were fit to quadratic response surface models (QRSM) using polynomial functions in the doses of the two components. Using QRSM, seated systolic (SeSBP) and diastolic blood pressure (SeDBP) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied. Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP. Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg. Coadministration of Fos and HCTZ produced an additive antihypertensive effect. This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology.

Adult↗
PubMed1996

Comparison of plasma lipid and lipoprotein profiles in hypertensive black versus white men. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

An abnormal plasma lipid and lipoprotein profile is an independent and strong predictor of mortality and morbidity from coronary artery disease (CAD). We report on plasma lipid and lipoprotein profiles with respect to race, age, obesity, blood pressure (BP), smoking, and drinking history in 1,292 male veterans with a diastolic BP of 95 to 109 mm Hg while off antihypertensive medications. Blacks had 24% (p <0.001) lower triglycerides than whites. In contrast, the following parameters were higher in blacks than in whites by the indicated percentages: high-density lipoprotein (HDL) cholesterol, 16% (p <0.001); HDL2 cholesterol, 36% (p <0.001); apolipoprotein (Apo) A1, 8% (p <0.001); HDL/low-density lipoprotein (LDL), 18% (p = 0.018); HDL2/LDL, 36% (p = 0.031); HDL2/HDL3, 21% (p <0.001); and Apo A1/Apo B, 15% (p <0.001). Triglycerides were unchanged up to age 60, but were lower by 24% (p <0.001) in those aged > or = 70. Apo A1 levels were higher (p <0.001), whereas LDL cholesterol was lower (p <0.008) in moderate alcohol consumers versus abstainers. Triglycerides were higher (p <0.001), whereas HDL, HDL2 cholesterol, and Apo A1 were lower (p <0.001) with increasing obesity. Moderate alcohol consumption had a strong favorable effect on HDL, HDL2, and HDL3 cholesterol among subjects of normal weight, but this effect was diminished in obese subjects. Total and LDL cholesterol were higher by 6.4% (p = 0.001) and 9.4% (p <0.003), respectively, whereas HDL cholesterol remained unchanged in those with diastolic BP of 105 to 109 mm Hg versus those with diastolic BP of 95 to 99 mm Hg. We conclude that hypertensive black men have lipid and lipoprotein profiles indicative of less CAD risk than white men. Chronic moderate alcohol consumption correlates with a favorable plasma lipid and lipoprotein profile in normal, but not obese, men. Obesity is associated with an adverse plasma lipid and lipoprotein profile. Thus, race, alcohol intake, and obesity may be important modifiers of CAD in untreated hypertensive men.

Apolipoprotein A-I↗
PubMed1996

Evidence for the efficacy of low-dose diuretic monotherapy.

Diuretic monotherapy has been recommended by the fifth report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC-V) as a preferred initial treatment for hypertension. Thiazide diuretics are commonly used to treat hypertension because of their demonstrated efficacy, favorable safety profile, low acquisition cost, and their proven ability to reduce blood pressure-related morbidity and mortality. Once-daily low-dose hydrochlorothiazide (12.5 mg/ day) or chlorthalidone (15 mg/day) effectively reduces blood pressure in patients with stage 1 or stage 2 hypertension in comparison with placebo. Blood pressure reductions with low-dose hydrochlorothiazide and chlorthalidone are comparable to that achieved with higher doses (25 and 50 mg/day). Additional blood pressure reductions can be attained with concomitant use of once-daily low-dose hydrochlorothiazide or chlorthalidone with an angiotensin-converting enzyme (ACE) inhibitor, a beta blocker, or a calcium antagonist. Once-daily low-dose hydrochlorothiazide provides clinically meaningful blood pressure lowering while minimizing adverse effects, such as electrolyte disturbances, cholesterol elevations, and increases in serum uric acid levels.

Chlorthalidone↗
PubMed1996

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents↗
PubMed1995

Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.

Adult↗
PubMed1995

Department of veterans Affairs single-drug therapy of hypertension study. Revised figures and new data. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

The antihypertensive efficacy of six drugs and placebo was compared in 1292 men with untreated diastolic blood pressure of 95 to 109 mm Hg. The primary end point "success" was defined as the patient having achieved a diastolic blood pressure of < 90 mm Hg at the end of the drug titration period and having maintained a diastolic blood pressure of < 95 mm Hg for 1 year without drug intolerance. The original published success rate data (N Engl J Med 1993;328:914-921) were discovered to be in error due to a computer programming code omission (N Engl J Med 1994;330:1689). This paper presents corrected graphic figures. The corrected success rates were generally higher than originally published. Overall, diltiazem (72%) was significantly higher than hydrochlorothiazide (55%), prazosin (54%), captopril (50%), and placebo (31%); clonidine (62%) and atenolol (60%) were intermediate. There were some changes in the hierarchy of drug response, but important differences in success rates according to age by race subgroups remained. Whites responded well to all drug classes, except for lower efficacy of hydrochlorothiazide in younger whites. Blacks responded better to diltiazem than other agents. In addition, we have analyzed the data using a definition of success based on < 90 mm Hg for 1 year. Use of the <90 mm Hg criterion reduced the rate of success, but had only a minor effect on the drug success rate hierarchy. We conclude that single-drug antihypertensive therapy is effective in a majority of stage 1 to 2 diastolic hypertensive patients, although there are important age-by-race differences in success rates among various drug classes.

Adult↗
PubMed1995

Relative benefits of different antihypertensive drugs in the prevention of vascular complications.

Large-scale clinical trials of antihypertensive drugs that have shown a reduction in morbidity and mortality used the classic step-care treatment design, initiating treatment with a diuretic. Long-term morbidity and mortality reports comparing the newer classes of agents with the traditional antihypertensive agents have not been completed. A recent meta-analysis of 13 randomized, controlled clinical trials of hypertension showed that 18 elderly people, but two to four times as many younger people, needed to be treated for 5 years to prevent one cerebrovascular or cardiac event. Any head-to-head comparisons of one class of antihypertensive agent with another in the prevention of vascular complications will require very large cohorts, even of elderly people, to show a difference. Such trials are ongoing or being planned, but their results will not be available before the next century.

Aged↗
PubMed1995

Optimising diuretic therapy in elderly patients with hypertension.

Hypertension is the most important risk factor for cardiovascular events in the elderly and it is present in more than 50% of acculturated populations over 60 years of age. Morbidity trials have clearly demonstrated the benefits of treating hypertension in the elderly in all subgroups examined, including diabetics, those over 80 years of age, those with or without electrocardiographic abnormalities, and in both men and women. These reductions in strokes, coronary events, and other hypertensive complications have been seen primarily with diuretic-based regimens, with or without potassium-sparing therapy. However, in the 1990s physicians are initiating diuretics less often for older patients with hypertension in spite of this scientific evidence. Low doses of diuretics have been well tolerated, successful in recent morbidity trials, and avoid much of the concerns about theoretical toxicities from diuretics, although higher doses have also been shown to reduce cardiovascular events. Until calcium channel blockers, angiotensin converting enzyme inhibitors, alpha-blockers, or some other class of antihypertensive agent has been demonstrated to be at least as effective as diuretics in reducing cardiovascular events or mortality, diuretics should be the first drug class to consider for the treatment of hypertension in the elderly.

Aged↗
PubMed1995

Results of combination anti-hypertensive therapy after failure of each of the components. Department of Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents.

We randomised ambulatory men with diastolic blood pressure (BP) 95-109 mmHg without anti-hypertensive medication to single drug treatment with either hydrochlorothiazide 12.5-50 mg/day, atenolol 25-100 mg/day, captopril 25-100 mg/day, clonidine 0.2-0.6 mg/day, diltiazem-SR 120-360 mg/day, prazosin 4-20 mg/day or placebo in a double-blind prospective trial. The assigned drug was titrated to a goal BP of < 90 mm Hg. Patients not achieving goal BP were rerandomised to an alternative single active drug. Non-responders to the second drug received the first drug in combination with the second. Of the 102 non-responders to both drugs who qualified for the combination, 59 (57.8%) responded. The combination pairs that included a diuretic achieved diastolic goal BP in 69% and < 140 mm Hg systolic in 77% compared with 51% and 46%, respectively, for those combinations without a diuretic (P = 0.067; P = 0.002). Six of the eight terminations due to adverse drug reactions were in combinations containing prazosin; three of these six were hypotensive reactions. We conclude that two single drugs of insufficient efficacy to control BP individually have a high probability of achieving goal BP when combined, especially if the combination contains a diuretic.

Adolescent↗
PubMed1994

Prevention and Treatment of Hypertension Study (PATHS). Rationale and design.

Alcohol consumption has been recognized as an important correlate of blood pressure in many epidemiologic studies, but few interventional studies have been conducted to examine the effect of a reduction in alcohol intake on blood pressure. Because these studies have usually included few subjects and been of short duration, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Veterans Affairs (VA) Cooperative Studies Program have initiated a randomized, controlled, multicenter trial to determine whether blood pressure and left ventricular mass are lowered over 6 months of alcohol moderation in non-dependent moderate to heavy drinkers (three or more drinks per day average but not alcohol dependent) with above-average normal (80 to 89 mm Hg) and mildly hypertensive (90 to 99 mm Hg) levels of diastolic blood pressure, and whether a reduction in alcohol intake can be maintained for 2 years. Eligible veterans are randomized to either an alcohol reduction intervention or a control observation group at seven clinical sites. The projected sample size is 580 participants. Alcohol intake is assessed by self-report using a retrospective diary (Chronological Drinking Record) and by various biochemical markers, including apolipoproteins, HDL cholesterol (and subfractions), and carbohydrate deficient transferrin, analyzed at a central laboratory. The alcohol intervention technique is a cognitive-behavioral program, the intensive phase of which consists of six counseling sessions over 3 months. Echocardiograms are obtained at baseline and 6 months after randomization. This trial has important implications for both the prevention and treatment of hypertension.

Adult↗
PubMed1994

Hypertension in the elderly.

Hypertension is the most important risk factor for cardiovascular events in the elderly, and it is present in more than 50% of the American population over 60 years of age. Both systolic and diastolic blood pressure are directly related to increasing cardiovascular risk and systolic pressure becomes even more important in the elderly. Borderline isolated systolic hypertension confers an 80% likelihood of developing definite hypertension over 20 years, as well as a higher risk for cardiovascular events. The morbidity trials in the elderly, especially the Systolic Hypertension in the Elderly Program, have clearly demonstrated the benefits of treating hypertension in the elderly in all subgroups examined. Although these benefits have been seen with diuretic (and to a lesser extent beta-blocker) regimens, physicians initiated therapy less often with these drugs during 1990 and 1991. All of the major classes of drugs are effective in lowering blood pressure in older whites, and calcium antagonists and diuretics are most effective in older black patients.

Aged↗
PubMed1994

Endurance exercise in mild hypertension: effects on blood pressure and associated metabolic and quality of life variables.

The effects of a ten week endurance exercise training programme on blood pressure and associated metabolic and quality of life variables were examined in 28 unmedicated mildly hypertensive men (21-54 years of age). At baseline, BP averaged 138.8/94.8 mmHg, body mass index averaged 27.9 and percentage body fat averaged 29%. The average reduction in BP of 11.4/9.8 mmHg (P = 0.0001) was accompanied by decreases in plasma renin activity of 1.82 ng/ml/h (P = 0.001) and in total plasma catecholamines of 77.9 pg/ml (P = 0.05). Percentage body fat decreased 1.3% (P = 0.02) and work capacity increased 1.2 METS (P = 0.002). There were no significant changes in body weight or plasma lipids, cortisol, insulin or urinary electrolyte excretion. Changes in SBP were correlated significantly with change in plasma renin activity (r = 0.38, P = 0.05). Favourable changes were also observed in mood (P = 0.04) and in one measure of type A behaviour (P = 0.04). None of the participants sustained an injury. We conclude that reduction of BP with endurance exercise training in these mildly hypertensive men was primarily associated with reduced plasma renin activity and did not adversely affect quality of life.

Adolescent↗
PubMed1993

Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors. METHODS: In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS: The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks (< 60 years) and older blacks (> or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. CONCLUSIONS: Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.

Age Factors↗
PubMed1993

Systolic hypertension in the elderly. Safe treatment with low-dose thiazide diuretics.

Low doses of thiazide diuretics are effective in controlling isolated systolic hypertension in most elderly patients. These agents are well tolerated and do not appear to adversely affect quality of life. Biochemical adverse effects are minimal with low doses. Of greatest importance, thiazide diuretics are the only class of antihypertensives that has been shown to reduce risk of cardiovascular events in patients with isolated systolic hypertension. Recent studies showed all these advantages with both chlorthalidone and hydrochlorothiazide therapy, although low-dose hydrochlorothiazide may cause less hypokalemia in the elderly than does chlorthalidone.

Aged↗