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Biomedical subjects

Marcus Flather

Publications and source records attributed to Marcus Flather.

At least 19 recordsLinked to original sources
PubMed2006

Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study.

AIMS: Randomized trials have not demonstrated coronary heart disease benefit from hormone replacement therapy (HRT). We hypothesized that low-dose HRT may avoid harm. METHODS AND RESULTS: We studied the effects of HRT on lipids and coagulation in women with acute coronary syndromes. A total of 100 post-menopausal women >55 years were enrolled between 2 and 28 days after an acute coronary syndrome and randomized to oral oestradiol-17beta 1 mg plus norethisterone acetate 0.5 mg daily, or matching placebo, and followed for up to 12 months. Levels of lipids, lipoproteins, and haemostasis markers were measured at baseline, 3, and 6 months. There were no significant differences in lipid levels between the two groups, probably due to concomitant statin use. Antithrombin and factor VII levels were significantly lower in the HRT group, whereas fibrinogen was significantly decreased in the placebo group. No evidence of increased coagulation activation was observed, nor of adverse cardiovascular outcomes [odds ratio (OR) 0.63 (95% confidence intervals 0.31-1.31)]. CONCLUSION: Low-dose HRT may give cardiovascular benefit. These findings require confirmation in a full clinical trial with evaluation of cardiovascular outcomes as the primary objective.

Aged↗
PubMed2006

Protocol for the Arterial Revascularisation Trial (ART). A randomised trial to compare survival following bilateral versus single internal mammary grafting in coronary revascularisation [ISRCTN46552265].

BACKGROUND: Standard coronary artery bypass graft surgery uses a single internal mammary artery and supplemental vein or radial artery grafts. Several observational studies have suggested a survival benefit with two internal mammary artery grafts compared to a single internal mammary artery graft, but this has not been tested in a randomised trial. The Arterial Revascularisation Trial is a Medical Research Council and British Heart Foundation funded, multi-centre international trial comparing single internal mammary artery grafting versus bilateral internal mammary artery grafting. METHODS/DESIGN: Twenty centres in the UK, Australia, Poland and Brazil are planning to randomise 3000 coronary artery bypass graft surgery patients to single or bilateral internal mammary artery grafting. Supplemental grafts may be either saphenous vein or radial artery. Coronary artery bypass grafting can be performed as an on-pump or off-pump procedure. The primary outcome is survival at 10 years and secondary end-points include clinical events, quality of life and cost effectiveness. The effect of age, left ventricular function, diabetes, number of grafts, vein grafts and off-pump surgery are pre-specified subgroups. DISCUSSION: The Arterial Revascularisation Trial is one of the first randomised trials to evaluate the effects on survival and other clinical outcomes of single internal mammary artery grafting versus bilateral internal mammary artery grafting, and will help to establish the best approach for patients requiring coronary artery bypass graft surgery.

Journal Article↗
PubMed2006

Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis.

RATIONALE: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence. OBJECTIVES: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations. METHODS: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo. MEASUREMENTS AND MAIN RESULTS: Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo. CONCLUSIONS: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Administration, Inhalation↗
PubMed2006

Generalizing results of randomized trials to clinical practice: reliability and cautions.

BACKGROUND: Well designed randomized controlled trials provide reliable evidence of treatment effects, but there is no consensus on how best to apply these results to clinical practice. The main concerns are that populations enrolled in trials are more selected than those treated in a clinical setting, and whether the treatment effects observed in trials will also be observed in clinical practice. METHODS: An informal literature review was undertaken to find studies analysing the issue of generalizing trial results (external validity) to clinical practice. RESULTS: Most of the studies focused on differences in patients characteristics (age, gender, severity of disease, concomitant treatments and so on) between the clinical trial population and a 'real world' clinical population. None provided good evidence of a reduction in the treatment effect in the trial compared to what might happen in clinical practice for simple pharmacological treatments. However complex treatments like surgery or percutaneous interventional procedures, had a greater potential for variation. Extrapolating treatments to different health care settings from the trial can result in important variations in treatment effects. CONCLUSIONS: Complex therapies need careful consideration before they can be applied routinely from trials into practice, and applying results from one health care environment to a different one should be carried out with caution. Generalizing results from well conducted trials to clinical practice can mostly be carried out with confidence, especially for simple therapies with good evidence of benefit.

Humans↗
PubMed2006

[The Chinese registry on reperfusion strategies and outcomes in ST-elevation myocardial infarction].

OBJECTIVE: To analyze the current use of reperfusion strategies and the outcomes of patients with ST elevation acute coronary syndromes (ACS) in China. METHODS: A total of 518 consecutive patients (371 male and 147 females, mean age 65 +/- 11) with ST elevation ACS or newly discovered left bundle branch block were registered from 20 hospitals from 5 regions (ranging from large regional centre hospitals to small county hospitals) in China. Patient general characteristics, reperfusion patterns and outcomes were analyzed. Patients were followed up for 3 months. RESULTS: The median time from pain onset to presentation at the hospital was 4 hours. Pre-hospital delay > 12 hours was found in 20% patients. Fifty-six percent patients (292/518) underwent reperfusion therapy (134 with primary percutaneous coronary intervention and 158 with fibrinolysis). The median time from admission to reperfusion (door-to-needle) was 65 min in fibrinolysis group and 110 min (door-to-cath) in primary PCI group respectively. Urokinase was used in 67% (106/158) patients underwent fibrinolysis. Multivariate logistic regression analysis showed that age >/= 75 years (P < 0.01), previous myocardial infarction (P < 0.01) and history of congestive heart failure (P < 0.05) were associated with no reperfusion therapy. Mortality and congestive heart failure rates were significantly higher in patients with no reperfusion therapy not only at discharge (P < 0.01) but also at 3 months (P < 0.01) compared to patients underwent reperfusion. The incidence of combined outcomes (death or MI, and death, MI or Strobe) was also higher in patients without reperfusion therapy at 3 months (all P < 0.01) compared to patients underwent reperfusion. There were no differences on combined outcomes between fibrinolysis and primary PCI subgroups. CONCLUSION: Reperfusion therapy was the primary treatment of choice to improve the outcomes of patients with ST elevation ACS. Strategies to increase reperfusion therapy rate for ST elevation ACS are urgently needed in China.

Aged↗
PubMed2005

Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass.

BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.

Aged↗
PubMed2005

Early versus periprocedural administration of abciximab for primary angioplasty: a pooled analysis of 6 studies.

BACKGROUND: The 2004 ACC/AHA guidelines on ST-elevation myocardial infarction state that it is reasonable to start treatment with abciximab as early as possible before primary percutaneous coronary intervention (PCI). We investigated the potential benefit of early use of abciximab by pooling data from all the available studies. METHODS: Six prospective studies were identified that had allocated 260 patients to receive early abciximab (either prehospital or soon after the patient arrived in hospital) and 342 to receive late abciximab (at the time of PCI). RESULTS: TIMI flow grade 2 or 3 was present in 42% of the early group compared with 29% in the late group (P = .001). After PCI, 59% of patients in the early group showed ST-resolution >or = 70%, compared with 41% in the late group (P = .003). The composite clinical outcomes death, new myocardial infarction, or repeat target vessel revascularization at 30 days occurred in 7.3% of the early group compared with 9.7% in the late group (odds ratio 0.73, 95% CI 0.41-1.32) and death alone occurred in 2.7% versus 4.7%, respectively (odds ratio 0.56, 95% CI 0.23-1.39). CONCLUSIONS: Early administration of abciximab improves epicardial patency (TIMI flow) before PCI and results in better myocardial tissue perfusion (ST-resolution) after the procedure. The promising effects on clinical outcomes need to be tested in larger studies.

Abciximab↗
PubMed2004

The clinician as investigator: participating in clinical trials in the practice setting.

The rapid development of new drugs, therapies, and devices has created a dramatic increase in the number of trials needed to properly evaluate them. The majority of patients treated today, many of whom could be eligible for participation in these studies, are seen in community hospitals and medical practices that are not affiliated with an academic medical center. Thus, there is a demonstrable need for physicians in private practice to enlist as investigators in these trials. This article is intended to encourage those physicians by describing the need and providing the rationale for their participation. It covers basic requirements for participating in clinical trials and outlines ethical, regulatory, financial, and other logistical issues of importance for the potential investigator and provides an algorithm for selecting a study for participation. Finally, the appendices review basic elements of study design and statistical principles, which may be of interest to a potential investigator.

Choice Behavior↗
PubMed2004

Determinants of successful endoscopic internal thoracic artery harvesting: a prospective analysis.

OBJECTIVE: Endoscopic internal thoracic artery (ITA) harvesting is employed during minimal-access coronary artery bypass grafting. To improve case selection, we prospectively analyzed our entire experience to identify variables that predict intraoperative conversion to sternotomy. METHODS: We performed a prospective study from September 1999 to November 2003 of 100 consecutive patients with an endoscopically harvested left ITA (LITA). Success was defined as an endoscopic dissection of the LITA sufficient to reach the anastomosis. Multivariate logistic regression analysis was performed to identify independent preoperative and procedural predictors of success. RESULTS: The measured parameters (mean +/- SD) were age (62 +/- 9 years), height (174 +/- 9 cm), weight (81 +/- 14 kg), and logistic Euroscore (2.0 +/- 1.7). Patients comprised 8 (8%) women, 17 (17%) with urgent operations, 42 (42%) with multiple vessel disease, 17 (17%) with a left ventricular ejection fraction <50%, 2 (2%) redo procedures, and 3 (3%) with pleural disease. The Zeus robot was used in 17 patients (17%). Eight-eight (88%) of the LITA were successfully harvested endoscopically. Among the 12 patients who underwent conversions, pleural adhesions were the most common finding (n = 4, 33%). One LITA was unusable. In the final multivariate model, lung disease was a negative predictor of successful endoscopic harvest (odds ratio, 0.13; 95% confidence interval, 0.02-0.63; P =.012). The variables of age, sex, left ventricular function, logistic Euroscore, operative priority, and use of the Zeus robot did not achieve statistical significance. CONCLUSIONS: Acceptable conversion rates and low conduit wastage are achievable during a unit's initial experience. Lung disease is associated with increased conversion frequency, and surgeons embarking on endoscopic harvesting should consider excluding these patients to improve their chances of success. Pleural adhesions increase the technical difficulty of surgery.

Coronary Artery Bypass↗
PubMed2004

A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery.

BACKGROUND: The effect of the use of coronary-artery bypass surgery without cardiopulmonary bypass and cardiac arrest ("off pump") on graft patency remains uncertain. We undertook a prospective, randomized, controlled study to compare graft-patency rates and clinical outcomes in off-pump surgery with conventional, "on-pump" surgery. METHODS: We randomly assigned 50 patients to undergo on-pump coronary-artery bypass grafting and 54 to undergo off-pump surgery. Surgical and anesthetic techniques were standardized for both groups. Clinical outcomes and troponin T levels were measured. Three months later, the patients underwent coronary angiography, including quantitative analysis. RESULTS: The mean age of the patients was 63 years, and 87 percent were men. The on-pump group received a mean of 3.4 grafts, and the off-pump group 3.1 (P=0.41). There were no deaths. There was no significant difference in the median postoperative length of stay between the two groups (seven days in each group). The area under the curve of troponin T levels was higher during the first 72 hours in the on-pump group than in the off-pump group (30.96 hr x microg per liter vs. 19.33 hr x microg per liter, P=0.02). At three months, 127 of 130 grafts were patent in the on-pump group (98 percent), as compared with 114 of 130 in the off-pump group (88 percent, P=0.002). The patency rate was higher for all graft territories in the on-pump group than in the off-pump group. CONCLUSIONS: In this randomized study, off-pump coronary surgery was as safe as on-pump surgery and caused less myocardial damage. However, the graft-patency rate was lower at three months in the off-pump group than in the on-pump group, and this difference has implications with respect to the long-term outcome.

Aged↗
PubMed2004

Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI).

BACKGROUND: Most patients with acute myocardial infarction (AMI) are admitted to hospitals without percutaneous transluminal coronary angioplasty (PTCA) facilities or are initially managed in a prehospital mobile unit. Thrombolysis remains the most readily available reperfusion treatment in those settings, but the optimal subsequent strategy in those patients is unclear. If a mechanical recanalization is likely to be performed in an emergency, it is probably desirable that the patient receives abciximab, the glycoprotein IIb/IIIa antagonist with the strongest evidence of benefit for angioplasty in AMI. OBJECTIVE: The aim of this trial is to compare the effects on clinical outcome and cost-effectiveness of 2 strategies after immediate treatment with abciximab and half-dose reteplase for ST-elevation AMI: to manage the patients conservatively (referring them for rescue PTCA only if needed) or to immediately send all patients for emergency coronary angioplasty. METHODS: The Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) is an open, prospective, randomized, multicenter clinical trial conducted in patients with high-risk ST-segment elevation AMI treated within 12 hours from symptom onset in hospitals without PTCA facilities or in a prehospital mobile intensive care unit. Apart from contraindications to thrombolysis, the main exclusion criteria are age > or =75 years and a past history of CABG surgery or a percutaneous coronary intervention procedure involving the infarct-related artery. Enrollment will be performed in hospitals without PTCA facilities or directly in the ambulance if a dedicated system is in place for prehospital diagnosis and treatment of AMI. Patients will receive half-dose reteplase and full-dose abciximab and will subsequently be randomized to conventional medical therapy (with referral for emergency rescue PTCA allowed in selected cases) or emergency angioplasty. The primary end point is the 30-day combined incidence of mortality, reinfarction, and refractory ischemia. In order to obtain a 95% power (2-sided) to detect a 42% reduction in the primary end point, 900 patients are required in each arm of the study. Secondary end points include the 1-year composite end point of mortality, reinfarction, refractory ischemia, and hospital readmission because of heart failure; resource use at 30 days and 1 year; and the incidence of inhospital stroke and bleeding complications in the 2 groups. RESULTS: Seventy-four patients have been randomized (as of March 10, 2004); results are expected in June 2005. CONCLUSION: This study will establish whether angioplasty must be started as soon as possible in all patients who receive combined pharmacologic reperfusion with the glycoprotein IIb/IIIa inhibitor abciximab and half-dose thrombolysis or whether it can be postponed or skipped in patients with signs of successful reperfusion, with obvious organizational advantages.

Abciximab↗
PubMed2004

Influence of valve prosthesis type on the recovery of ventricular dysfunction and subendocardial ischaemia following valve replacement for aortic stenosis.

BACKGROUND: Long-standing aortic stenosis (AS) causes significant progressive left ventricular (LV) dysfunction and may result in subendocardial ischaemia. Following aortic valve surgery, LV function may improve and this may be accompanied by reversal of ischaemia. There is debate about the differential effects of valve substitutes. METHODS: We studied 33 patients with significant AS and impaired LV systolic function. Patients underwent trans-thoracic Doppler echocardiography and 12-lead electrocardiography pre-operatively, prior to discharge from hospital and at 2.5 (range 1.5-3) years follow-up. RESULTS: Twenty patients received a stentless valve and 13 a stented valve. No patient had significant aortic regurgitation, other valvular disease or coronary artery disease. LV fractional shortening (FS) increased from 19+/-6% to 26+/-7% post-operatively and to 33+/-12% at follow-up in the stentless group (p<0.001). In the stented group, no significant change was seen in the post-operative FS, although it improved at follow-up and at this point did not differ from the stentless group. LV mass fell from 338+/-72 to 265+/-64 g post-operatively and to 170+/-77 g at follow-up (p<0.001) in the stentless group, whereas in the stented group a significant fall was seen only at follow-up (329+/-51 g pre-operatively, 304+/-68 g post-operatively, 166+/-28 g at follow-up, p=0.01). LV free wall excursion increased from 0.8+/-0.3 to 1.1+/-0.4 cm (p=0.05) and to 1.4+/-0.3 cm (p=0.02 compared with pre-operative values) in the stentless group. In the stented group, values were 1.0+/-0.4, 1.0+/-0.3 and 1.3+/-0.2 cm (p=0.05 compared with pre-operative) at the three time points, respectively. QRS duration fell from 113+/-36 ms pre-operatively to 99+/-12 ms at follow-up in the stentless group and from 117+/-28 to 99+/-19 ms in the stented group, p=0.01 for both comparisons. QT interval fell from 385+/-54 ms pre-operatively to 366+/-39 ms at follow-up (p=0.04) in the stentless group with no significant change in the stented group (387+/-52 and 375+/-33 ms, p=0.24). There was reversal of LV strain pattern in 11 (55%) of the stentless group and 6 (46%) of the stented group and normalisation of the inverted U wave in two thirds of patients. CONCLUSION: In patients with AS and severe LV dysfunction, there is a more rapid improvement in LV function following aortic valve replacement with a stentless prosthesis. Improvements in those receiving stented valves appear delayed, although there were no differences between the groups in LV function or mass at follow-up. Normalisation of LV free wall systolic behaviour, narrowing of the QRS complex and a reduction in the QT interval suggest that AS is associated with subendocardial ischaemia that reverses following valve replacement.

Aortic Valve↗
PubMed2004

Improved recovery after the endoscopic atraumatic coronary artery bypass procedure compared with sternotomy for off-pump bypass of the left internal thoracic artery to the left anterior descending coronary artery: a case-matched study.

OBJECTIVE: The endoscopic atraumatic coronary artery bypass (endo-ACAB) procedure allows single-vessel coronary artery bypass grafting (CABG), avoiding sternotomy or thoracotomy. We set out to define the effect of this surgical approach on postoperative recovery, blood loss, and return to work. METHODS: We performed a case-control comparison of our first 29 endo-ACAB procedures for left anterior descending coronary artery (LAD) disease against 29 control patients, who underwent off-pump beating heart CABG via sternotomy for isolated LAD disease in the same institution. Control pairs were matched for age, sex, and ventricular function. RESULTS: In a matched population, endo-ACAB is associated with shorter postoperative ventilation times (6.2 hours versus 9.0 hours, P = .034) and hospital stays (5.3 nights versus 6.4 nights, P = .04), less blood loss (363.9 mL versus 570.3 mL, P = .017), and lower transfusion requirements. Endo-ACAB patients were more likely to return to employment and did so at a mean of 6.6 weeks earlier than sternotomy patients (P = .019). CONCLUSIONS: Endo-ACAB for grafting of the left internal mammary artery to the LAD is associated with reduced blood loss and faster postoperative recovery. Avoiding sternotomy appears to be a significant factor in recovery after beating heart single-vessel CABG surgery.

Anastomosis, Surgical↗
PubMed2004

Effects of valve replacement on left ventricular function in patients with aortic regurgitation and severe ventricular disease.

BACKGROUND AND AIM OF THE STUDY: Longstanding aortic regurgitation (AR) can result in left ventricular (LV) dysfunction that may reverse after aortic valve replacement (AVR). Stentless valves may result in a more rapid recovery in function due to a more physiological flow and lower outflow resistance. METHODS: The effect of AVR on LV function was studied in 47 patients who received either a stentless (n = 33) or stented (n = 14) valve for isolated AR. All patients had evidence of pre-existing LV dysfunction (end-systolic dimension (ESD) >50 mm). Patients were studied using transthoracic echocardiography at baseline, postoperatively, and at 2.5-year follow up. RESULTS: Preoperatively, there were no differences in LV dimensions. The end-diastolic dimension fell from 75 +/- 10 mm to 61 +/- 10 mm postoperatively and to 52 +/- 10 mm at follow up in the stentless group (p <0.001), and ESD fell from 54 +/- 10 mm to 36 +/- 8 mm at follow up (p <0.001). There were no significant early changes in patients who received stented valves, though LV dimensions fell at follow up. Fractional shortening (FS) increased from 25 +/- 8% in the postoperative period to 31 +/- 7% in the stentless group (p <0.001), but there was no change in the stented group (20 +/- 7% versus 23 +/- 8%). In the stentless group, LV mass fell from 366 +/- 104 g to 276 +/- 68 g postoperatively and to 219 +/- 79 g at follow up (p <0.001); there was no postoperative change in the stented group, though a late reduction occurred, from 349 +/- 51 g preoperatively to 265 +/- 61 g at follow up (p = 0.06). CONCLUSION: For patients with AR and LV dysfunction, AVR with a stentless prosthesis offers early reductions in LV dimensions, improved LV function, and regression of LV mass. In patients who received a stented valve, these improvements were delayed and less complete. Hence, for some patients with AR and LV dysfunction, a stentless prosthesis may be preferable.

Adult↗