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Biomedical subjects

C M Hawkins

Publications and source records attributed to C M Hawkins.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Decision rules for predicting future lipid values in screening for a cholesterol reduction clinical trial.

Recent large clinical trials have required screened patients to have serial measurements of an entry criteria variable, eliminating patients form further consideration if the average value is not in the eligibility range specified by the trial protocol. The increasing costs of large clinical trials required that they be executed efficiently. One way to improve efficiency would be to reduce the number of required screening measurements for a patient likely to be ineligible. A procedure is proposed that predicts the value of an average based on n measurements serially obtained on a patient during the screening phase when only m < n measurements are available. The employment of this procedure in a large clinical trial that uses low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglycerides as entry criteria during the screening process is described. As a second example, this procedure is applied to population screening for lipid levels above a treatment threshold. The National Cholesterol Education Program recommends that the average of two LDL cholesterol measurements be used to determine whether LDL cholesterol is above 130 mg/dl, the threshold for treating patients with coronary heart disease. However, data from a sample of patients from a postinfarction population suggest that, if a single LDL cholesterol is above 146 mg/dl, the probability is greater than 95% that the average of the two LDL cholesterol measurements will be above 130 mg/dl.

Adult↗
PubMed1995

Effect of atenolol and reserpine on selected events in the systolic hypertension in the elderly program (SHEP).

The effect of atenolol and reserpine on incidence of strokes, coronary heart disease (CHD), cardiovascular disease (CVD), and mortality was assessed in 4736 persons aged 60 years and older with isolated systolic hypertension. Participants were randomized to either chlorthalidone (2371), with step-up to atenolol, or reserpine if needed, or placebo (2365). The average baseline SBP/DBP was 170/77 mm Hg. In the active treatment group, step 1, dose 1 was chlorthalidone, 12.5 mg/day; dose 2 was 25 mg/day. For step 2, dose 1 was atenolol 25 mg/day (or reserpine 0.05 mg/day if atenolol was contraindicated); dose 2 was 50 mg/day (reserpine, 0.10 mg/day). During 4.5 years average follow-up, 32% (757) of the active treatment group were on atenolol, with an average exposure of two years and 8% (193) were on reserpine with an average exposure of 1.7 years. Overall there were 96 strokes, 140 CHD events and 289 CVD events among the 2365 active group participants. Using time-dependent lifetable regression with adjustment for several variables, the addition of either atenolol or reserpine to chlorthalidone did not substantially alter the risk ratios for chlorthalidone alone. The relative risk for CHD events for atenolol versus no atenolol was 1.04 (95% confidence interval: 0.58, 1.86) and for reserpine versus no reserpine was 0.93 (95% confidence interval: 0.29, 2.96). The relative risk for atenolol were 0.84 (95% confidence interval: 0.54, 1.30) for death, 1.34 (95% confidence interval: 0.80, 2.28) for stroke, and 1.07 (95% confidence interval: 0.71, 1.61) for CVD. For reserpine, the corresponding relative risks and confidence intervals were 0.65 (0.26, 1.59) for death, 0.27 (0.04, 2.26) for stroke, and 0.55 (0.20, 1.49) for CVD. Thus, the beneficial effects in several outcomes in Systolic Hypertension in the Elderly Program (SHEP) were due to the treatment regimen of lowering blood pressure based on low-dose chlorthalidone (plus atenolol or reserpine as required to meet blood pressure criteria). Additional (independent) benefits attributable to atenolol or to reserpine were not identified. However, a greater number of patients might have been necessary to adequately evaluate potential differential effects of these drugs, especially for reserpine.

Aged↗
PubMed1993

Statistical considerations in monitoring the Systolic Hypertension in the Elderly Program (SHEP).

The Systolic Hypertension in the Elderly Program (SHEP), a randomized, double-masked, placebo-controlled trial of 4736 persons, was designed to assess the efficacy of antihypertensive drug treatment to reduce the risk of fatal and nonfatal strokes among people age 60 and over with isolated systolic hypertension. The statistical method used in interim monitoring of results was conditional power (or stochastic curtailment). The findings did not become conclusive until near the completion of the trial, and therefore SHEP was continued to its scheduled closing date. The trial demonstrated a 36% reduction in the incidence of stroke in the active treatment group (P = .0003). In addition to evaluating overall efficacy of treatment, the monitoring process considered such other issues as nonstroke outcomes, lag time between first report of stroke and final confirmation of stroke diagnosis, consistency of results across subgroups, and completeness of follow-up. The purpose of this article is to review these factors with primary emphasis on the statistical aspects.

Aged↗
PubMed1993

Conclusions and implications of the systolic hypertension in the elderly program.

Isolated systolic hypertension has a higher prevalence with age and an associated excess cardiovascular risk. The Systolic Hypertension in the Elderly Program (SHEP) was a randomized, prospective, double blind clinical trial to assess the efficacy and safety of a antihypertensive regimen based on low dose diuretic therapy in reducing the five year combined incidence of fatal and nonfatal stroke. SHEP demonstrated a significant 36% reduction in stroke incidence. Also, 27% reduction in coronary heart disease incidence and a 32% reduction in major cardiovascular disease incidence were achieved. The benefits accrued to all subgroups identified based on baseline age, race, sex, blood pressure, serum cholesterol levels, and ECG abnormalities. A low-dose diuretic regimen should be the initial treatment of choice for most hypertensive patients, based on demonstrated reduction in risk for major cardiovascular events, its safety, acceptance by patients, and low cost.

Age Factors↗
PubMed1992

Analysis of a clinical trial involving a combined mortality and adherence dependent interval censored endpoint.

Clinical trials often involve a variety of clinical and laboratory measures that are used as endpoints and sometimes two of these measures are combined in one endpoint. When the individual components of such a combined endpoint are 'time to event' measurements, the analysis is straightforward if each of the components is measured frequently and regularly over time. However, the analysis of the combined endpoint is more difficult when one component of the endpoint is right censored and the other is interval censored. This paper describes a statistic, based on a rank ordering of events for such a combined measure. The power of the test statistic is explored.

Clinical Trials as Topic↗
PubMed1992

Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group.

We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.

Atenolol↗
PubMed1991

Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained.

Adult↗
PubMed1991

Effect of antihypertensives on sexual function and quality of life: the TAIM Study.

OBJECTIVE: To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies. DESIGN: Multicenter, randomized, placebo-controlled clinical trial. SETTING: Three university-based tertiary care centers. PATIENTS: Patients (697) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight. INTERVENTION: Patients were stratified by clinical center and race and were randomly assigned to one of three diets (usual, low-sodium and high-potassium, weight loss) and one of three agents (placebo, chlorthalidone, and atenolol). MEASUREMENTS: Changes in measures of sexual problems, distress, and well-being after 6 months of therapy were analyzed. MAIN RESULTS: Low-dose chlorthalidone and atenolol produced few side effects, except in men. Erection-related problems worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%; CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of life most, reducing total physical complaints (P less than 0.001) and increasing satisfaction with health (P less than 0.001). Total physical complaints decreased in 57% to 76% of patients depending on drug and diet group, and were markedly decreased by weight loss. CONCLUSION: In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men.

Adult↗
PubMed1991

Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis.

The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted.

Health Services for the Aged↗
PubMed1990

Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status.

OBJECTIVE: To evaluate the 6-month change in cardiovascular (coronary heart disease) risk as a function of diet and drug therapy for mild hypertension. DESIGN: Collaborative randomized, controlled clinical trial to assess the efficacy of alternative regimens in treating mild hypertension. SETTING: Three university-based tertiary care centers-the Trial of Antihypertensive Interventions and Management (TAIM). PATIENTS: Six hundred and ninety-two men and women ages 21 to 65 years with diastolic blood pressure between 90 and 100 mm Hg and weight between 110% and 160% of ideal weight. MEASUREMENTS AND MAIN RESULTS: Patients stratified by clinical center and race were randomized into diet (usual, low sodium-high potassium, weight loss) and drug (placebo, chlorthalidone, and atenolol) groups resulting in nine diet plus drug combinations. The cardiovascular risk at 6-month follow-up was estimated relative to baseline in 692 participants using the Framingham Study model. Due to the blood pressure reduction, cardiovascular risk declined from baseline for all treatment groups (except the usual diet plus chlorthalidone group because of increased cholesterol levels). The relative cardiovascular risk at 6 months compared to baseline ranged from 0.83 in the weight loss plus atenolol subgroup to 1.03 in the usual diet plus chlorthalidone subgroup. The active drug plus weight loss groups showed the lowest relative cardiovascular risk at 6 months. CONCLUSIONS: Mild hypertension was generally reduced to desirable levels within 6 months by monotherapy. Evaluating blood pressure changes together with the risk factors indicated a differential effect on overall cardiovascular risk depending on the diet and drug used. Dietary therapy, particularly weight reduction, was important adjunctive treatment in reducing overall cardiovascular risk.

Adrenergic beta-Antagonists↗
PubMed1990

Quality of life on antihypertensive therapy: a randomized double-blind controlled trial of captopril and atenolol.

A randomized double-blind study lasting 2 months was performed with either 25 mg captopril twice a day or 50 mg atenolol once a day in 125 patients with established diastolic hypertension (diastolic blood pressure greater than 95 mmHg) identified during a population screening programme of subjects aged less than 65 years. Quality of life was assessed from self-completed questionnaires. A significant fall in diastolic blood pressure occurred with both captopril (106.7 +/- 7.0 to 98.6 +/- 8.6 mmHg) and atenolol (107.4 +/- 7.5 to 98.2 +/- 8.1 mmHg) but there was no difference between the two drugs in the size of the fall. A measure of the number of symptomatic complaints, the symptom complaint rate, decreased with both drugs, by 1.3% for captopril and 3.1% for atenolol, but the difference between the drugs was not significant [1.8%; 95% confidence interval (Cl) - 1.3%, 4.9%]. There was a significant increase in the reporting of cough and runny nose in those on captopril compared with atenolol. A health index increased by 1.1% with captopril in comparison with no change on atenolol (difference 1.1%; 95% Cl - 2.0%, 4.2%). Psychological well-being was measured using the Symptom Rating Test. The improvement in total score was 1.4% with captopril and 2.3% with atenolol. The difference of 0.9% was not statistically significant (95% Cl - 1.2%, 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗
PubMed1989

Trial of antihypertensive interventions and management. Design, methods, and selected baseline results.

The Trial of Antihypertensive Interventions and Management was a multicenter randomized, placebo-controlled trial designed to assess the effectiveness of various combinations of pharmacologic and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90-100 mmHg). The primary outcome was blood pressure change between baseline and 6 months. The study consisted of a 3 X 3 factorial design wherein participants were randomly allocated to nine drug-diet treatment groups. Drugs included placebo, diuretic, and beta-blocker. Diets were usual, weight loss, and low sodium/high potassium. The basic strategy was to address clinical questions of interest by comparing mean blood pressure changes of selected drug-diet combinations. This paper describes the study including experimental design, sample size considerations, statistical analysis, organizational structure, and baseline findings.

Adult↗
PubMed1989

The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension (ISH) [systolic blood pressure (SBP) greater than or equal to 160 mmHg, diastolic blood pressure (DBP) less than 90 mmHg] reduces the 5 year incidence of fatal and nonfatal stroke. Between March 1, 1985 and January 15, 1988, 4736 persons (target 4800) with ISH, age 60 years and over, were enrolled. Potential participants met blood pressure (BP) and age criteria. Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued, and then met BP criteria (33% of cohort). Stepped-care therapy with chlorthalidone and atenolol (alternative, reserpine) or matching placebos was initiated as first and second steps. At baseline the trial population was 43.1% male, 56.9% female; 13.9% black, 86.1% non-black. Also, the mean age was 71.6 years; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg; 59.8% had codeable resting electrocardiographic abnormalities. The trial is now in follow-up phase with scheduled termination in 1991.

Aged↗
PubMed1989

The effects of verapamil and propranolol on quality of life in hypertension.

Quality of life was evaluated in a four-month randomised double-blind trial of verapamil compared with propranolol in the treatment of hypertension in 94 patients in the UK. Scores on a health status index, measuring activity and perceived health, increased in verapamil patients compared to a decrease in propranolol patients (P = 0.01). Measures of psychiatric morbidity also tended to improve with verapamil and deteriorate with propranolol. Propranolol patients reported more symptoms overall compared with verapamil (P less than 0.05). The prevalence of certain symptoms--headaches, weak limbs and slower walking pace, increased significantly with propranolol compared with verapamil, but constipation was more common in verapamil patients (P less than 0.05). After four months, diastolic blood pressure averaged 86.2 mmHg with verapamil and 90.3 mmHg with propranolol (P = 0.02). However, this difference in final blood pressure did not explain the more favourable quality of life scores with verapamil, and the data suggest that health-related well-being is higher with this drug.

Adult↗
PubMed1989

An illness-death process with time-dependent covariates.

A general model for the illness-death stochastic process with covariates has been developed for the analysis of survival data. This model incorporates important baseline and time-dependent covariates in order to make an appropriate adjustment for the transition and survival probabilities. The follow-up period is subdivided into small intervals and a constant hazard is assumed for each interval. An approximation formula is derived to estimate the transition parameters when the exact transition time is unknown. The method developed is illustrated with data from a study on the prevention of the recurrence of a myocardial infarction and subsequent mortality, the Beta-Blocker Heart Attack Trial (BHAT). This method provides an analytical approach with which the effectiveness of the treatment can be compared between the placebo and propranolol treatment groups with respect to fatal and nonfatal events simultaneously.

Biometry↗
PubMed1988

The relation between degree of blood pressure reduction and mortality among hypertensives in the Hypertension Detection and Follow-Up Program.

The relation between degree of diastolic blood pressure reduction and mortality was examined among hypertensive persons in the Hypertension Detection and Follow-up Program. This program, conducted from 1973-1979, was a multicenter community-based trial, which followed 10,940 hypertensive participants for five years. The one-year annual visit was the first occasion on which change in blood pressure could be measured on all participants. During the subsequent four years of follow-up on 10,053 participants, 568 deaths occurred. With time-dependent life tables and time-dependent Cox life table regression analyses, the existence of a quadratic function which modeled the relation between diastolic blood pressure reduction and mortality was supported, even after adjusting for other risk factors. The minimum mortality hazard ratio, based on a particular model, occurred at a diastolic blood pressure reduction of 26.2 mmHg (standard error = 13.4) in the whole population and 10.0 mmHg (standard error = 5.3) in the baseline diastolic blood pressure stratum 90-104 mmHg. After this reduction, there was a small increase in the risk of death. There was no evidence of the quadratic function after fitting the same model with systolic blood pressure. Methodological issues involved in studying a particular degree of blood pressure reduction were considered. The confidence interval around the change corresponding to the minimum hazard ratio was wide, and the obtained blood pressure level should not be interpreted as a goal for treatment. Blood pressure reduction was attributed not only to pharmacologic therapy but also to regression to the mean, and to other factors unrelated to treatment.

Actuarial Analysis↗