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Biomedical subjects

A E Fletcher

Publications and source records attributed to A E Fletcher.

At least 19 recordsLinked to original sources
PubMed2002

Prevalence of visual impairment in people aged 75 years and older in Britain: results from the MRC trial of assessment and management of older people in the community.

AIMS: To measure the prevalence of visual impairment in a large representative sample of people aged 75 years and over participating in the MRC trial of assessment and management of older people in the community. METHODS: 53 practices in the MRC general practice research framework. Data were obtained from 14 600 participants aged 75 years and older. Prevalence of visual impairment overall (binocular visual acuity <6/18) which was categorised separately into low vision (binocular visual acuity <6/18-3/60) or blindness (binocular visual acuity of <3/60). The prevalence of binocular acuity <6/12 was presented for comparison with other studies. Visual acuity was measured using Glasgow acuity charts; glasses, if worn, were not removed. RESULTS: Visual acuity was available for 14 600 people out of 21 241 invited (69%). Among people with visual acuity data, 12.4% overall (1803) were visually impaired (95% confidence intervals 10.8% to 13.9%); 1501 (10.3%) were categorised as having low vision (8.7% to 11.8%), and 302 (2.1%) were blind (1.8% to 2.4%). At ages 75-79, 6.2% of the cohort were visually impaired (5.1% to 7.3%) with 36.9% at age 90+ (32.5% to 41.3%). At ages 75-79, 0.6% (0.4% to 0.8%) of the study population were blind, with 6.9% (4.8% to 9.0%) at age 90+. In multivariate regression, controlling for age, women had significant excess risk of visual impairment (odds ratio 1.43, 95% confidence interval 1.29 to 1.58). Overall, 19.9% of study participants had a binocular acuity of less than 6/12 (17.8% to 22.0%). CONCLUSION: The results from this large study show that visual impairment is common in the older population and that this risk increases rapidly with advancing age, especially for women. A relatively conservative measure of visual impairment was used. If visual impairment had been defined as visual acuity of <6/12 (American definition of visual impairment), the age specific prevalence estimates would have increased by 60%.

Age Factors↗
PubMed2001

Randomised comparison of three methods of administering a screening questionnaire to elderly people: findings from the MRC trial of the assessment and management of older people in the community.

OBJECTIVE: To compare three different methods of administering a brief screening questionnaire to elderly people: post, interview by lay interviewer, and interview by nurse. DESIGN: Randomised comparison of methods within a cluster randomised trial. SETTING: 106 general practices in the United Kingdom. PARTICIPANTS: 32 990 people aged 75 years or over registered with participating practices. MAIN OUTCOME MEASURES: Response rates, proportion of missing values, prevalence of self reported morbidity, and sensitivity and specificity of self reported measures by method of administration of questionnaire for four domains. RESULTS: The response rate was higher for the postal questionnaire than for the two interview methods combined (83.5% v 74.9%; difference 8.5%, 95% confidence interval 4.4% to 12.7%, P<0.001). The proportion of missing or invalid responses was low overall (mean 2.1%) but was greater for the postal method than for the interview methods combined (4.1% v 0.9%; difference 3.2%, 2.7% to 3.6%, P<0.001). With a few exceptions, levels of self reported morbidity were lower in the interview groups, particularly for interviews by nurses. The sensitivity of the self reported measures was lower in the nurse interview group for three out of four domains, but 95% confidence intervals for the estimates overlapped. Specificity of the self reported measures varied little by method of administration. CONCLUSIONS: Postal questionnaires were associated with higher response rates but also higher proportions of missing values than were interview methods. Lower estimates of self reported morbidity were obtained with the nurse interview method and to a lesser extent with the lay interview method than with postal questionnaires.

Aged↗
PubMed2001

Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension.

The objective of this study was to compare quality of life and incidence of dry persistent cough among patients treated with eprosartan and enalapril for mild-moderate hypertension. This was a randomised 26-week double-blind controlled trial carried out in clinics in nine countries of North America, Europe and South Africa. A total of 529 patients aged 18 and over with diastolic blood pressure between 95 mm Hg and 114 mm Hg were studied. Treatment comprised of eprosartan or enalapril monotherapy for 12 weeks with the option of hydrochlorothiazide addition for the remaining 14 weeks. The primary outcome measures were cough and the Psychological General Wellbeing Index (PGWB) total and subscales (anxiety, self-control, depression, general health, positive wellbeing and vitality). The results were that 17.8% of enalapril patients and 13.2% of eprosartan patients withdrew from randomised treatment. Those on enalapril were twice as likely to have gained a definite or possible cough by study end point as those on eprosartan (7.6% vs 3.2%) P = 0.099. At monotherapy end point the differences were greater (9.9% vs 2.1%) and of statistical significance, P = 0.001. Patients treated with enalapril, however, had small but significant improvements in measures of self-control and total PGWB compared with those on eprosartan. The effect sizes of 0.2 or less indicated that there were small differences. In conclusion eprosartan was associated with fewer coughs than enalapril but it performed less well on some aspects of quality of life.

Acrylates↗
PubMed2001

Quality of life and cough on antihypertensive treatment: a randomised trial of eprosartan, enalapril and placebo.

The objective of this study was to compare the quality of life and incidence of dry cough with the angiotensin II antagonist eprosartan, the ACE-inhibitor enalapril, and placebo, in hypertensive patients with a history of ACE-inhibitor cough. The study was a multicentre, randomised, double-blind, parallel group controlled trial. A total of 136 patients judged to have ACE-inhibitor cough during single-blind enalapril treatment which was lost during a subsequent placebo washout phase, were randomised to receive either eprosartan 300 mg twice daily, or enalapril 20 mg once daily, or placebo for 6 weeks. Self-completion questionnaires assessing quality of life and cough were examined at baseline and end of study. At study end point 23% of patients in the enalapril group and 5% in the eprosartan and placebo groups reported cough (which included definite, probable and possible coughs) (P = 0.02). After adjusting for multiple comparisons, the eprosartan group was not significantly different from either placebo or enalapril. There were no significant differences in the Psychological General Wellbeing Index (PGWB). In conclusion the incidence of self-reported cough on eprosartan was similar to that on placebo, and lower than on enalapril but this difference was not significant when adjustments were made for multiple comparisons. There were no differences in quality of life.

Acrylates↗
PubMed2001

Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux.

Inhibitory gamma-aminobutyric acid (GABA)(A) receptors are subject to modulation at a variety of allosteric sites, with pharmacology dependent on receptor subunit combination. The influence of different alpha subunits in combination with beta3gamma2s was examined in stably expressed human recombinant GABA(A) receptors by measuring (36)Cl influx through the ion channel pore. Muscimol and GABA exhibited similar maximal efficacy at each receptor subtype, although muscimol was more potent, with responses blocked by picrotoxin and bicuculline. Receptors containing the alpha3 subunit exhibited slightly lower potency. The comparative pharmacology of a range of benzodiazepine site ligands was examined, revealing a range of intrinsic efficacies at different receptor subtypes. Of the diazepam-sensitive GABA(A) receptors (alpha1, alpha2, alpha3, alpha5), alpha5 showed the most divergence, being discriminated by zolpidem in terms of very low affinity, and CL218,872 and CGS9895 with different efficacies. Benzodiazepine potentiation at alpha3beta3gamma2s with nonselective agonist chlordiazepoxide was greater than at alpha1, alpha2, or alpha5 (P < 0.001). The presence of an alpha4 subunit conferred a unique pharmacological profile. The partial agonist bretazenil was the most efficacious benzodiazepine, despite lower alpha4 affinity, and FG8205 displayed similar efficacy. Most striking were the lack of affinity/efficacy for classical benzodiazepines and the relatively high efficacy of Ro15-1788 (53 +/- 12%), CGS8216 (56 +/- 6%), CGS9895 (65 +/- 6%), and the weak partial inverse agonist Ro15-4513 (87 +/- 5%). Each receptor subtype was modulated by pentobarbital, loreclezole, and 5alpha-pregnan-3alpha-ol-20-one, but the type of alpha subunit influenced the level of potentiation. The maximal pentobarbital response was significantly greater at alpha4beta3gamma2s (226 +/- 10% increase in the EC(20) response to GABA) than any other modulator. The rank order of potentiation for pregnanolone was alpha5 > alpha2 > alpha3 = alpha4 > alpha1, for loreclezole alpha1 = alpha2 = alpha3 > alpha5 > alpha4, and for pentobarbital alpha4 = alpha5 = alpha2 > alpha1 = alpha3.

Allosteric Regulation↗
PubMed2001

Do socioeconomic disadvantages persist into old age? Self-reported morbidity in a 29-year follow-up of the Whitehall Study.

OBJECTIVES: This study examined (1) the relation of employment grade in middle age to self-reported poor health and functional limitations in old age and (2) whether socioeconomic status at approximately the time of retirement modifies health differentials in old age. METHODS: Survivors of the Whitehall Study cohort of men were resurveyed. Respondents were aged 40 to 69 years when they were originally screened in 1967 to 1970. RESULTS: Compared with senior administrators, men in clerical or manual (low-grade) jobs in middle age had quadruple the odds of poor physical performance in old age, triple the odds of poor general health, and double the odds of poor mental health and disability. At most, 20% of these differences were explained by baseline health or risk factors. Men who moved from low to middle grades before retirement were less likely than those who remained in low grades to have poor mental health. CONCLUSIONS: Socioeconomic status in middle age and at approximately retirement age is associated with morbidity in old age.

Activities of Daily Living↗
PubMed2000

Bisoprolol and nifedipine retard in elderly hypertensive patients: effect on quality of life.

Subjects over the age 60 with sustained sitting diastolic pressures of 95-115 mm Hg were randomised to a regime based on bisoprolol (n = 368) or nifedipine retard (n = 379) for 24 weeks. The goal diastolic pressure was < or =90 mm Hg and to achieve this, double-blind medication could be doubled (5/10 mg bisoprolol, 40/80 mg nifedipine retard) or hydrochlorothiazide 25 mg (unblinded) could be added to the higher dose. In an intention-to-treat analysis, 309 subjects in both the bisoprolol and nifedipine retard treated group provided at least a baseline and a second quality of life assessment (82%). An excess of symptoms was observed in the nifedipine group for oedema of the legs, nocturia, constipation, racing heart and heart thumping. Fewer patients reported wheeze in the nifedipine group. For quality of life, there were no statistically significant differences between the two groups after 8 weeks. However, when analysing the results of the last available assessment (usually at 24 weeks) there were significant (P < 0.05) improvements in tension/anxiety, anger/ hostility, vigour/activity, and confusion/bewilderment, assessed by the Profile of Mood States (POMS) in patients receiving bisoprolol in comparison to those receiving nifedipine retard. The Sickness Impact Profile and objective tests of cognitive function did not differ statistically between the two groups. Quality of life was maintained at a good level on both treatments with advantages for bisoprolol in certain areas. Journal of Human Hypertension (2000) 14, 205-212.

Adrenergic beta-Agonists↗
PubMed1999

1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.

After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1, 3-dihydroimidazol-2-yl)piperidine 8. Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot" procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1, 3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or 5-position of the 1, 3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater selectivity (>1000-fold) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has >1000-fold selectivity over all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D(4) receptor.

Animals↗
PubMed1999

Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

BACKGROUND: Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. METHODS: After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly. RESULTS: At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively). CONCLUSIONS: Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.

Aged↗
PubMed1999

Low uptake of eye services in rural India: a challenge for programs of blindness prevention.

OBJECTIVES: To investigate service uptake in a rural Indian population served by outreach eye camps and to identify barriers to uptake. PARTICIPANTS AND METHODS: A routine eye camp was conducted within 5 km of each of 48 randomly selected villages of typically Hindu, backward-caste communities. Subsequently, participatory rural appraisal-community mapping, focus groups, matrix ranking, and semistructured interviews-was undertaken to explore community views of eye problems. An eye examination was conducted on persons with eye problems who did not attend the eye camp. Predictors of attendance were identified by multilevel regression analysis. RESULTS: Of 749 adults with an eye problem, 51 (6.8%) attended the eye camp. Independent predictors of attendance were being male (odds ratio = 2.3; 95% confidence interval, 1.2-4.5) and living within 3 km of the camp (odds ratio = 4.5; 95% confidence interval, 1.7-12.5). Of the 552 persons who did not attend the eye camps and had an eye examination, 242 (43.8%) had low vision (visual acuity <6/18 to > or =3/60 in presenting better eye) and 38 (6.9%) were blind in both eyes. Cataract surgery was recommended for 197 (35.8%) of the persons who did not attend the eye camps. Of 109 persons with a previous cataract operation, 42 (38.5%) had low vision and 11 (10.1%) were blind. Fear (principally of eye damage), cost (direct and indirect), family responsibilities, ageism, fatalism, and an attitude of being able to cope (with low or no vision) were the principal barriers to attending the eye camps. CONCLUSIONS: A high proportion of people who could have benefited from eye treatment were not using available services. Poor visual outcomes were observed in surgically treated persons.

Attitude to Health↗
PubMed1999

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Aged↗
PubMed1999

Symptoms reported by elderly patients with isolated systolic hypertension: baseline data from the SYST-EUR trial. Systolic Hypertension in Europe.

OBJECTIVES: To determine the symptomatic well-being of elderly persons with isolated systolic hypertension. DESIGN AND SETTING: Well-being determined during the placebo run-in period prior to entry to the Systolic Hypertension in Europe (SYST-EUR) trial. SUBJECTS: 641 People, 60 years or older with an average sitting blood pressure of 173/86 mm Hg. OUTCOME MEASURES: 33 Symptomatic complaints determined by a standard interview. RESULTS: The 437 women complained of 25% of the symptoms and the 204 men 21% (P<0.001). A markedly higher prevalence was observed in women compared with men for: pain in the joints of the hands (35% of women complained of this against 22% of men); 'racing heart' (33% against 17%); dry eyes (16% against 6%); blurring of vision (35% against 23%); cramps in the legs (43% against 31%); and a sore throat (15% against 7%). Nocturia was the most frequent complaint (68% in both sexes). Eight symptoms increased with age and one (rash) tended to decline. With increasing systolic pressure women also reported more headaches, unsteadiness, blurring of vision, irregular heart beat and 'racing heart' but, of these, only headaches increased with diastolic pressure. These observations were made after adjusting for age, blood sugar and body mass index (BMI) and were not observed in men. Higher blood sugars were associated with mouth ulcers, 'racing heart', blurring of vision and cramps in the legs. A higher BMI was associated with six symptoms, and a lower age of leaving education with eight. In men, alcohol consumption was related to 'racing heart', and smoking to wheezing and having a dry cough. CONCLUSIONS: A high level of complaint was associated with female gender, increasing age, blood sugar and BMI and a low age of leaving education.

Aged↗
PubMed1998

Visual acuity and quality of life outcomes in patients with cataract in Shunyi County, China.

PURPOSE: To measure visual acuity and vision-related quality of life in individuals in rural China operated on for cataract. METHODS: Five thousand fifty-two persons age 50 years and older, 90.9% (5,052/5,555) of a randomly selected population in Shunyi County, were examined in the fall of 1996. Visual functioning and quality of life questionnaires were administered to those with presenting visual acuity less than 6/60 in either eye and to those who were aphakic or pseudophakic. RESULTS: Of the 87 individuals operated on for cataract, 12% (10/87) had presenting visual acuity of 6/18 or more in both eyes, and 24.1% (21/87) had less than 6/60. Twenty-five percent (29/116) of the 116 eyes operated on for cataract had presenting visual acuity of 6/18 or more, and 44.8% (52/116) had less than 6/60. Aphakic cases without glasses and uncorrectable aphakia attributable to surgical complications were common. In a multivariate regression model, including time period of surgery, hospital type, and surgical procedure, only pseudophakia was associated with better outcomes (P = .05). On a scale from 0 (maximum problems) to 100 (no problems), the mean visual functioning score (+/-SD) for the operated-on population was 61.9 +/- 30.0, and 71.0 +/- 31.8 for the quality of life questionnaire. These scores were comparable to those of the unoperated-on population with moderate bilateral blindness (<6/60 to > or =3/60 in the better eye). Visual functioning and quality of life scores were closely correlated with visual acuity in operated-on (r = 0.64 and r = 0.61, respectively) and unoperated-on populations (r = 0.68 and r = 0.59, respectively). CONCLUSIONS: Both clinical and patient-reported cataract surgery outcomes are below what should be achievable. Improvement in outcomes must be given greater emphasis if the potential of cataract surgery in restoring sight is to be realized.

Aged↗
PubMed1998

Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor.

Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved.

Antipsychotic Agents↗
PubMed1998

Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.

OBJECTIVE: To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. DESIGN: Cross-sectional analyses at entry to a randomized controlled trial. SETTING: Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. PATIENTS: Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. MAIN OUTCOME MEASURES: Cognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework). RESULTS: Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. CONCLUSIONS: At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.

Age Factors↗
PubMed1998

Quality of life in chronic heart failure: cilazapril and captopril versus placebo. Cilazapril-Captopril Multicentre Group.

OBJECTIVE: To measure quality of life (QOL) in patients with mild to moderate heart failure treated with angiotensin converting enzyme (ACE) inhibitors cilazapril or captopril. DESIGN: Randomised, double blind, placebo controlled, parallel groups trial. SUBJECTS: 367 patients with New York Heart Association (NYHA) heart failure class II (62%), III (36%) or IV (1%). METHODS: Patients were randomised to receive cilazapril 1 mg daily (n = 191) or captopril 25 mg three times daily (n = 90) for 24 weeks, or placebo for 12 weeks followed by cilazapril 1 mg daily for a further 12 weeks (n = 86). If patients had not responded after four weeks cilazapril was increased to 2.5 mg daily and captopril to 50 mg three times daily. QOL was assessed at baseline, 12, and 24 weeks using the sickness impact profile (SIP), the profile of mood states (POMS), the Mahler index of dyspnoea-fatigue, and a health status index (HSI). RESULTS: The physical dimension of the SIP averaged 7 units at baseline and improved after 12 weeks by 2.24 units in the cilazapril group, 2.38 units in the captopril group, and 1.51 units in the placebo group. The difference between drug and placebo was therefore 0.73 units (95% CI -0.86 to 2.32) for cilazapril, and 0.87 units (95% CI -0.96 to 2.70) for captopril, with small non-significant effect sizes (a statistical method for estimating the importance of a treatment related change) of 0.12 and 0.14. Similar results were observed for the total POMS and HSI scores. Although QOL improved more on the ACE inhibitors than on placebo, the effect sizes were not significant (< or = 0.26). CONCLUSIONS: Improvements in QOL in mild to moderate heart failure were small when treated with cilazapril or captopril compared with placebo.

Adult↗
PubMed1998

Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension.

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P</=0. 01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P</=0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P</=0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension.

Aged↗