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Biomedical subjects

M Flather

Publications and source records attributed to M Flather.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics and treatments of patients with peripheral arterial disease referred to UK vascular clinics: results of a prospective registry.

BACKGROUND: Peripheral arterial disease (PAD) is often associated with risk factors including cigarette smoking, hypertension and hypercholesterolaemia, and patients have a high risk of future vascular events. Good medical management results in improved outcomes and quality of life, but previous studies have documented sub-optimal treatment of risk factors. We assessed the management of cardiovascular risk factors in patients with PAD referred to specialist vascular clinics. METHODS: This was a prospective, protocol driven registry carried out in UK vascular clinics. Patients who were first-time referrals for evaluation of PAD were eligible if they had claudication plus ankle-brachial pressure index (ABPI) < or = 0.9. Statistical associations between key demographic and treatment variables were explored using a chi-squared test. RESULTS: We enrolled 473 patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean estimated claudication distance was 100 m, and ABPI was 0.74. Mean systolic blood pressure (SBP) was 155 mmHg, and 42% had a SBP >160 mmHg. Forty percent were current smokers and half had tried to give up in the prior 6 months, but there was no evidence of a systematic method of smoking cessation. Mean total cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6 mmol/l. Antiplatelet therapy had been given to 70% and statins to 44%. Prior CHD was present in 29% and these patients had significantly higher use of antiplatelet therapy, statins and ACE-inhibitors. CONCLUSIONS: In spite of attempts to raise awareness about PAD as an important marker of cardiovascular risk, patients are still poorly treated prior to referral to a vascular clinic. In particular, the use of evidence-based treatments is sub-optimal, while hypertension and cigarette smoking are poorly managed. More work needs to be done to educate health professionals about the detection and optimal medical management of PAD.

Adult↗
PubMed2006

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Aged↗
PubMed2005

A cost-utility analysis of clopidogrel in patients with non-ST-segment-elevation acute coronary syndromes in the UK.

OBJECTIVE: To assess the long-term cost effectiveness of 1 year's treatment with clopidogrel on top of standard therapy (including aspirin; ASA) compared with standard therapy alone, in patients diagnosed with non-ST-segment-elevation acute coronary syndromes (ACS) in the UK. DESIGN: Cost utility analysis using a Markov model, incorporating clinical data from CURE (a multicentre randomised controlled trial, involving 12,562 patients) and data from UK observational studies. SETTING: Health economic evaluation carried out from the perspective of the UK NHS. PATIENTS: A representative cohort of 1000 UK patients aged 66 years, diagnosed with non-ST-segment-elevation ACS. INTERVENTIONS: Either a combination of 75 mg/day clopidogrel (300 mg loading dose, within 24 h prior to hospital admission) and standard therapy (including ASA, 75-325 mg/day) for 1 year followed by standard therapy alone for their remaining lifetime, or standard therapy alone (including ASA, 75-325 mg/day) for life. MAIN OUTCOME MEASURES: Incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: In the base case, the incremental cost effectiveness of the clopidogrel combination vs standard therapy alone is estimated as pounds 6991 per life-year gained and pounds 7365 per QALY gained. The probability that clopidogrel remains cost effective within the generally accepted pounds 30,000 per QALY threshold is more than 80%. The confidence interval around the relative risk for vascular death was identified as the main parameter affecting the estimated cost effectiveness. CONCLUSIONS: One year's treatment with clopidogrel is a cost effective intervention compared with standard therapy that should be considered as a routine treatment for patients with non-ST-segment-elevation ACS.

Acute Disease↗
PubMed2005

Life-style modification in peripheral arterial disease.

OBJECTIVE: To review the published evidence supporting the use of life-style modification in peripheral arterial disease (PAD). DESIGN: A systematic search of the medical literature was performed for relevant studies. MATERIALS: The publications obtained were then searched for randomised clinical trials which reported end-points of mortality or major cardiovascular event rates with various life-style modifications. RESULTS: Only one randomised controlled trial was found reporting relevant end-points. Other trials were of other end-points such as walking distance or biochemical markers. CONCLUSIONS: There is a lack of randomised controlled data proving the benefit of life-style modification in improving mortality and reducing cardiovascular events in patients with PAD. Despite this there is sufficient evidence to recommend some life-style modification as part of the overall approach to risk reduction in these patients. There is compelling evidence to support smoking cessation, increased exercise and improved diet.

Arterial Occlusive Diseases↗
PubMed2005

Pulmonary atresia with intact ventricular septum: predictors of early and medium-term outcome in a population-based study.

OBJECTIVES: Pulmonary atresia with intact ventricular septum is a form of congenital heart disease usually associated with right-heart hypoplasia, with considerable morphologic heterogeneity and often poor outlook. Ascertainment of risk factors for poor outcome is an important step if an improvement in outcome is to be achieved. METHODS: The UK and Ireland Collaborative study of Pulmonary Atresia with Intact Ventricular Septum is an ongoing population-based study of all patients born with this disease from 1991 through 1995. All available clinical, morphologic, and investigative variables were directly reviewed, and risk factor analysis was performed for poor outcome. RESULTS: One hundred eighty-three patients presented with pulmonary atresia with intact ventricular septum. Fifteen underwent no procedure, and all died. Of the remainder, 67 underwent a right ventricular outflow tract procedure (catheter or surgical), 18 underwent an outflow tract procedure with shunt, and 81 underwent a systemic-to-pulmonary shunt alone. One- and 5-year survival was 70.8% and 63.8%, respectively. Results from Cox proportional hazards model analysis showed that low birth weight (P = .024), unipartite right ventricular morphology (P = .001), and the presence of a dilated right ventricle (P < .001) were independent risk factors for death. The presence of coronary artery fistulae, right ventricular dependence, or the tricuspid valvar z score did not prove to be risk factors for death. After up to 9 years of follow-up, 29% have achieved a biventricular repair, 3% a so-called one-and-a-half ventricular repair, and 10.5% a univentricular repair, with 16.5% still having a mixed circulation (41% died). CONCLUSIONS: This population-based study has shown which features at presentation place an infant in a high-risk group. This is important information for counseling in fetal life and for surgical strategy after birth.

Follow-Up Studies↗
PubMed2005

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.

Acute Disease↗
PubMed2002

Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials.

OBJECTIVE: To summarise the current evidence from randomised controlled trials for diuretics in patients with congestive heart failure (CHF). DATA SOURCES: English-language randomised controlled trials and review papers referenced in Medline, Embase between 1966 and 1999. General literature review of pertinent journals was carried out and reference lists of papers were inspected. REVIEW METHOD STUDY DESIGN: Meta-analysis of randomised controlled trials of diuretic therapy in patients with CHF. STUDY SELECTION: Studies were included if they were randomised comparisons of loop or thiazide diuretics and control, or one diuretic and another active agent (e.g. ACE inhibitors, ibopamine and digoxin). DATA ABSTRACTION: Using a standardised protocol, two reviewers independently abstracted the data and assessed the methodological quality of each paper. DATA SYNTHESIS: The odds ratio (OR) of treated group compared with control was estimated for each end-point outcome and plotted against each other using the fixed-effects model. THE MAIN OUTCOME MEASURES: The primary outcomes of our analysis were effects of diuretics on mortality and morbidity. RESULTS: Eighteen trials met our criteria and were eligible for analysis, involving 928 patients. Eight trials were placebo-controlled. We analysed the data for mortality and for worsening heart failure. A further ten trials compared diuretics against other agents such as ACE inhibitors, ibopamine, and digoxin. Mortality data were available in three of the placebo-controlled trials (n=221); the mortality rate was lower for patients treated with diuretics than for control [the odds ratio for death, 0.25; 95% confidence intervals (CI), 0.07-0.84; P=0.03]. Admissions for worsening heart failure in the four small trials (n=448) showed an odds ratio of 0.31 (95% CI 0.15-0.62; P=0.001). In six studies of diuretics compared to active control, diuretics significantly improved exercise capacity in patients with CHF [OR: 0.37; CI: 0.10-0.64, P=0.007]. CONCLUSION: Compared to active control, diuretics appear to reduce the risk of worsening disease and improve exercise capacity. The available data from small studies show that in CHF conventional diuretics reduce the risk of death and worsening heart failure compared to placebo.

Diuretics↗
PubMed2001

ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology.

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Aged↗
PubMed2001

Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial.

BACKGROUND: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis. METHODS: In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care. FINDINGS: Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments. INTERPRETATION: Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.

Adolescent↗
PubMed2001

ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology.

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Algorithms↗
PubMed2001

Incremental importance of peak-exercise plasma levels of endothelin-1 and natriuretic peptides in chronic heart failure.

Chronic heart failure (CHF) studies investigating the clinical, hemodynamic, and therapeutic importance of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) are largely based on resting plasma levels, which may vary with prior exertion and postprandial status. This study investigated the importance of peak-exercise plasma levels of ET-1, ANP, and BNP in the assessment of left ventricular (LV) systolic function. Thirty-six male-patients ages 58 +/- 10 (mean +/- SD ) with NYHA class I-IV CHF due to coronary artery disease or idiopathic dilated cardiomyopathy were enrolled. LV systolic function was assessed by echocardiography and radionuclide ventriculography. Resting and peak cardiopulmonary exercise venous blood sampling and treadmill exercise testing were performed in the fasting state. Resting plasma levels of ET-1, ANP, and BNP were elevated compared with reference laboratory normal values. Exercise induced significant (p < 0.0001) increase in plasma levels of ET-1, ANP, and BNP. On univariate analysis peak-exercise plasma levels of ET-1, ANP, and BNP were more closely related to echocardiographically determined LV end-diastolic diameter and end-systolic diameter than their resting values. Multiple step-wise regression models identified resting and peak-exercise plasma levels of ET-1 and ANP but only the resting BNP as independent predictors of LV dimensions and systolic function. Peak exercise plasma levels of ANP and ET-1 are potentially more reliable and important than their resting levels as markers of LV systolic dysfunction and LV dimensions in patients with heart failure.

Aged↗