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Biomedical subjects

J McMurray

Publications and source records attributed to J McMurray.

At least 19 recordsLinked to original sources

Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.

Adrenergic beta-Antagonists↗

N-terminal pro B type natriuretic peptide, but not the new putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure.

OBJECTIVE: To determine whether the plasma concentration of the putative new cardiac hormone relaxin is predictive of clinical outcome in patients with chronic heart failure (CHF). DESIGN: Plasma relaxin and N-terminal pro B type natriuretic peptide (NT pro BNP) concentrations were measured in 87 patients admitted in an emergency with CHF caused by left ventricular systolic dysfunction. These were related to death and death or readmission with CHF over the following year. SETTING: Western Infirmary, Glasgow, UK. MAIN OUTCOME MEASURES: Plasma concentrations of relaxin and NT pro BNP; time to death or hospitalisation caused by heart failure. RESULTS: Plasma concentrations of both relaxin and NT pro BNP were greatly increased. Of the 43 patients with NT pro BNP above the group median concentration, 23 (53%) died and 30 (70%) died or were hospitalised with CHF. Among the 44 with concentrations below the median, these numbers were 5 (11%) and 12 (27%), respectively (p < 0.0001 and p < 0.0001, respectively). Plasma NT pro BNP concentration remained an independent predictor of an adverse clinical outcome in a multivariate analysis. Of the 42 patients with a relaxin concentration above the median, 13 (31%) died and 20 (48%) died or were hospitalised. Below the median, these numbers were 15 of 45 (33%) and 22 of 45 (49%) (p = 0.76 and p = 0.84, respectively). CONCLUSIONS: NT pro BNP is a powerful and independent predictor of outcome in CHF, whereas relaxin, also secreted by the heart in increased amounts in CHF, is not.

Aged↗

An audit of activity and outcome from a daily and a weekly "one stop" rapid assessment chest pain clinic.

OBJECTIVES: The recent National Service Framework for coronary heart disease advocates the establishment of rapid assessment clinics for chest pain. But how should these clinics be organised and do they fulfil their objectives? The aim of this study was to compare referral patterns to a daily and a weekly "one stop" rapid access chest pain clinic (RACPC), and to examine clinical outcome in patients attending these clinics. DESIGN: Patients were prospectively categorised into one of the following subgroups: "acute coronary syndrome", "stable coronary heart disease", or "low risk/non-coronary chest pain". Fatal and non-fatal outcomes were audited over eight months. SETTING: Both RACPCs were situated within the cardiology departments of two large Glasgow teaching hospitals. Patients were seen by a cardiologist, and underwent non-invasive testing. PARTICIPANTS: A total of 633 patients with chest pain who were referred by their general practitioner; 500 came to the daily and 133 to the weekly clinic. Forty four (7%) were categorised as having an acute coronary syndrome, 267 (42%) as stable coronary artery disease, and 322 (51%) as low risk/non-coronary chest pain. RESULTS: Referral patterns to the two clinics differed significantly. Compared with the weekly clinic, more patients with an acute coronary syndrome (7.8 v. 3.8%) and low risk/non-coronary chest pain (55.2 v. 35.6%), but fewer patients with stable coronary disease (37.0 v. 61.6%) were referred to the daily clinic (p<0.00001). During follow up eight (1.3%) patients died from a cardiac cause, and eight (1.3%) patients suffered a myocardial infarction. None of these patients were classified as low risk/non-coronary chest pain. CONCLUSIONS: (1) RACPCs do provide an effective tool for the early assessment of patients with possible angina. (2) The frequency with which clinics are scheduled may be an important factor in determining how the service is utilised in practice.

Aged↗

Effects of urotensin II in human arteries and veins of varying caliber.

BACKGROUND: -Urotensin II (UII) is the ligand for the GPR14 receptor and the most potent vasoconstrictor in the cynomolgus monkey. UII also contracts rat thoracic aorta. We studied the effect of human UII (hUII) in human blood vessels Methods and Results-Small subcutaneous resistance arteries, internal mammary arteries, saphenous veins, and small subcutaneous veins were studied using standard techniques. Subcutaneous resistance arteries constricted in response to norepinephrine (maximum tension, 2.84+/-0.38 mN/mm; the concentration required to produce 50% of the maximum response [EC(50)], 0.52+/-0.07 micromol/L) and endothelin-1 (maximum tension, 4.19+/-0.93 mN/mm; EC(50), 1.6+/-0.1 nmol/L). hUII did not contract these arteries, internal mammary arteries, or either type of vein, but it was a potent vasoconstrictor in rat thoracic aorta (maximum tension, 2.36+/-0.2 mN/mm; EC(50), 1.13+/-0.36 nmol/L). CONCLUSIONS: -hUII has no vasoconstrictor action in human arteries and veins of different sizes and vascular beds. Marked species differences in the actions of UII question its importance in human cardiovascular regulation.

Adult↗

Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was recently published, an update is required to include more current trials. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating congestive heart failure in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, ACE inhibitors, and beta blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis vs. no prior exposure; and patients with diastolic vs. systolic dysfunction. SEARCH STRATEGY: Electronic databases were searched between 1966 and 2000. Dissertation Abstracts and annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were searched from 1996-2000. In addition, reference lists provided by the pharmaceutical industry (Glaxo Wellcome Inc.) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic congestive heart failure who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of heart failure such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were reviewed by one of the coauthors, and validated by staff from the central office of the Heart Collaborative Review Group in Bristol, UK. MAIN RESULTS: Eleven articles meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon on 8, 4, and 10 of these selected studies, were recorded and analyzed. The data show that there is no difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. REVIEWER'S CONCLUSIONS: The literature indicates that digitalis has a useful role in the treatment of patients with congestive heart failure who are in normal sinus rhythm.

Cardiotonic Agents↗

Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: putting guidelines into practice.

Surveys of prescribing in both hospitals and primary care have shown delays in translating improved survival data from clinical trials into clinical practice thereby denying patients the benefits of proven treatments, such as the angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with clinical guidelines and concerns about adverse events. Recent trials have shown that substantial improvements in survival are associated with spironolactone and beta-blocker therapy. In order to accelerate the uptake of these treatments, and to ensure that all eligible patients should receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of heart failure. The objective of these recommendations is to provide practical guidance for non-specialists in order to support the implementation of evidenced-based therapy for heart failure. These practical recommendations are meant to supplement rather than replace existing guidelines.

Adrenergic beta-Antagonists↗

Explanation for the decline in coronary heart disease mortality rates in Auckland, New Zealand, between 1982 and 1993.

BACKGROUND: We sought to determine how much of the recent, substantial fall in coronary heart disease (CHD) mortality rates in New Zealand can be attributed to "evidence-based" medical and surgical treatments and how much can be attributed to cardiovascular risk factor reductions. METHODS AND RESULTS: A cell-based mortality model was developed and refined. This model combined (1) the published effectiveness of cardiological treatments and risk factor reductions with (2) data on all medical and surgical treatments administered to all CHD patients and (3) trends in population cardiovascular risk factors (principally smoking, cholesterol, and hypertension) from 1982 to 1993 in Auckland, New Zealand (population 996 000). Between 1982 and 1993, CHD mortality rates fell by 23.6%, with 671 fewer CHD deaths than expected from baseline mortality rates in 1982. Forty-six percent of this fall was attributed to treatments (acute myocardial infarction 12%, secondary prevention 12%, hypertension 7%, heart failure 6%, and angina 9%), and 54% was attributed to risk factor reductions (smoking 30%, cholesterol 12%, population blood pressure 8%, and other, unidentified factors 4%). These proportions remained relatively consistent after a robust sensitivity analysis. CONCLUSIONS: Approximately half the CHD mortality rate fall in Auckland, New Zealand, was attributed to medical therapies, and approximately half was attributed to reductions in major risk factors. These findings emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments and actively promotes a prevention program, particularly for smoking, diet, and blood pressure reduction.

Adult↗

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Aged↗

Intracavernous alprostadil alfadex is more efficacious, better tolerated, and preferred over intraurethral alprostadil plus optional actis: a comparative, randomized, crossover, multicenter study.

OBJECTIVES: To compare the efficacy, safety, and patient preference of intracavernously administered alprostadil alfadex and intraurethrally administered alprostadil. METHODS: A crossover, randomized, open-label multicenter study of 111 patients with erectile dysfunction of at least 6 months' duration compared the efficacy, safety, and patient preference of intracavernosal alprostadil (EDEX/Viridal) with MUSE plus optional ACTIS. All patients underwent an in-office dose titration with either drug before undertaking an at-home treatment phase. The most frequently used doses during the at-home phase were 40 microg (44.1% of men) and 1000 microg (86.8% of men) for EDEX and MUSE, respectively; the mean doses were 26.1 microg and 922.5 microg for EDEX and MUSE, respectively. RESULTS: More EDEX than MUSE administrations resulted in an erection sufficient for sexual intercourse (82.5% versus 53.0%); significantly more patients using EDEX achieved at least one erection sufficient for sexual intercourse (92.6% versus 61.8%; P <0.0001); and EDEX use resulted in a significantly greater percentage of patients attaining at least 75% of erections sufficient for sexual intercourse (75% versus 36.8%; P <0.0001). Penile pain was the most common side effect for both medications: 20.0% versus 30.5% (in-office) and 33.8% versus 25.0% (at-home) for EDEX and MUSE, respectively. Similar numbers of adverse events were reported with either treatment during the at-home phase. Patient and partner satisfaction was greater with EDEX, and more patients preferred this therapy, choosing to continue it during a patient preference period at the end of the study. CONCLUSIONS: Since intracavernous injection therapy was more efficacious, better tolerated, and preferred by the patients and their partners, it should be offered as the first-choice treatment if oral therapy fails or is contraindicated.

Adult↗