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Biomedical subjects

Mardi Gomberg-Maitland

Publications and source records attributed to Mardi Gomberg-Maitland.

14 recordsLinked to original sources
PubMed2006

Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials.

AIMS: The risk of stroke is greater among women with atrial fibrillation (AF) than men. Warfarin protects against stroke, but treatment-related bleeding occurs more often in women than in men. METHODS AND RESULTS: SPORTIF III (open label, n=3410) and V (double-blind, n=3922) included 2257 women with AF and one or more stroke risk factors randomized to warfarin [target international normalized ratio (INR) 2.0-3.0] or ximelagatran (36 mg twice daily). Primary outcomes were all stroke (ischaemic/haemorrhagic) and systemic embolic event. Women were older, on average, than men, 73.4+/-8.0 vs. 69.8+/-9.0 years (P<0.0001). More women were >75-years old and women had more risk factors than men had (P<0.0001). The INR on warfarin (mean 2.5+/-0.7) was within target range for 67% of follow-up regardless of gender. Women more often developed primary events [2.08%/year, 95% confidence interval (CI) 1.60-2.56%/year vs. 1.44%/year, 95% CI 1.18-1.71%/year in men; P=0.016). Major bleeding rates were similar (P=0.766) but women experienced more overall (major/minor) bleeding (P<0.001). Warfarin was associated with more overall bleeding in both genders and more major bleeding in women than in men (P=0.001). CONCLUSION: When compared with men with AF, women in these studies were older and had more stroke risk factors. Women were more prone to anticoagulant-related bleeding; the higher rate of thrombo-embolism among women was related to more frequent interruption of anticoagulant therapy.

Administration, Oral↗
PubMed2006

Three-dimensional transthoracic echocardiography to evaluate cor triatriatum in the adult.

Cor triatriatum is a rare congenital condition in which the left atrium is partitioned into two chambers by a fibrous or fibromuscular septum. The diagnosis is often made early in childhood, but can rarely be discovered later in adulthood. This delay in diagnosis is likely because of the number and size of the fenestrations in the septum. Echocardiography is the modality most often used to diagnose cor triatriatum. Generally, transesophageal echocardiography (TEE) is superior to transthoracic imaging. Three-dimensional echocardiography, however, is a modality that offers additional information not offered by 2-dimensional echocardiography. Although 3-dimensional TEE has previously been described, we report what we believe to be the first case of 3-dimensional transthoracic echocardiography used to diagnose cor triatriatum. This modality offers an advantage over TEE, as it allows the septum to be viewed easily without the risks or inconvenience of TEE.

Aged↗
PubMed2006

Endothelin receptor antagonism in pulmonary arterial hypertension--a role for selective ET(A) inhibition?

BACKGROUND: Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary arteries and is characterized by a progressive increase in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. A rapidly progressive disease with limited therapeutic options, PAH may progress to right ventricular failure and death. Endothelin (ET-1), a potent vasoconstrictor, has vascular remodeling properties that contribute to the acceleration of the disease. ET-1 predominantly binds to two receptors, endothelin-A (ET(A)) and endothelin-B (ET(B)) receptors. ET(A) receptors are found on smooth muscle cells only and, when activated, induce vasoconstriction and cellular proliferation. ET(B) receptors on smooth muscle cells, when activated, cause vasoconstriction, whereas those on endothelial cells produce vasodilation and clear circulating ET-1. Therefore, a clinically important question arises as to whether selective ET(A) receptor antagonism is superior to nonselective dual-receptor antagonism in the treatment of PAH. SCOPE: To review clinical trials that studied safety and efficacy of various endothelin receptor antagonists (ETRAs) for the treatment of PAH and address the rationale for the use of either a nonselective or a selective ETRA. FINDINGS: Nonselective blockade of both ET receptors with the ETRA bosentan has demonstrated benefit in PAH, as have sitaxsentan and ambrisentan, two investigational agents with more selectivity for the ET(A) receptor. Data from placebo-controlled studies and long-term, open-label studies suggest that all ETRAs have similar efficacy, though there is some evidence suggesting that selective ETRAs may have a safer profile. CONCLUSION: Both selective and nonselective ETRAs have proven to be efficacious in treatment of PAH patients, and selective ETRAs may have a slightly safer profile. However, because PAH is a rare disease and trials have relatively small numbers of patients, it is difficult to quantify the magnitude of the difference between the different agents.

Clinical Trials as Topic↗
PubMed2006

Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease for which both continuous IV epoprostenol and continuous subcutaneous treprostinil have proven effective. With continuous IV treprostinil having potential advantages over both of the above therapies, we investigated the safety and efficacy of this regimen in patients with PAH. METHODS: We conducted a 12-week, prospective, open-label, uncontrolled, multicenter study of continuous IV treprostinil in 16 patients with PAH that was idiopathic (n = 8), related to connective tissue disease (n = 6), or related to congenital heart disease (n = 2). The primary end point was change from baseline to week 12 in exercise capacity assessed by the 6-min walk (6MW) test. RESULTS: Continuous IV treprostinil increased 6MW distance (mean +/- SE) by 82 m from baseline (319 +/- 22 m) to week 12 (400 +/- 26 m) [n = 14; p = 0.001]. There were also significant improvements in the secondary end points of Naughton-Balke treadmill time (p = 0.007), Borg dyspnea score (p = 0.008), and hemodynamics (mean pulmonary artery pressure, p = 0.03; cardiac index, p = 0.002; pulmonary vascular resistance, p = 0.001) at week 12 compared with baseline. Side effects were mild and consistent with those reported with prostacyclin treatment. One death, unrelated to study drug, occurred during the 12-week study in a patient who received 3 days of treprostinil and died 2 weeks later. CONCLUSIONS: Long-term IV infusion of treprostinil is safe and appears to be effective for the treatment of patients with PAH.

Adult↗
PubMed2005

Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by abnormalities in endothelial and smooth muscle cell function. Prostacyclin released by endothelial cells is a potent vasodilator by increasing cyclic adenosine monophosphate. Sildenafil, an inhibitor of phosphodiesterase-5, increases cyclic guanosine monophosphate in the lungs, producing vasodilation. To test for a therapeutic benefit of the combination of a prostacyclin analogue, subcutaneous treprostinil, and sildenafil, a proof-of-concept, open-label investigational trial was initiated. Subjects with PAH in World Health Organization (WHO) functional classes II to IV receiving subcutaneous treprostinil for > or =6 months were evaluated with an exercise treadmill test using the Naughton-Balke protocol at baseline and after 12 weeks. Sildenafil 50 mg 3 times daily was added to the treprostinil. Mean treadmill times in seconds were compared before and after 12 weeks of therapy. Nine subjects enrolled in the trial; 7 were women (mean age 35 years). At baseline, 3 subjects were in WHO functional class II and 6 subjects were in WHO functional class III. The mean treadmill time at baseline was 465 +/- 167 seconds and at 12 weeks was 656 +/- 205 seconds (42% improvement, p = 0.049). All patients had symptomatic improvement. In conclusion, this pilot study of subcutaneous treprostinil with sildenafil for PAH suggests additive beneficial effects.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension.

RATIONALE: Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension. The prostacyclin analog treprostinil is also efficacious by subcutaneous infusion, is easier to administer, and has a longer half-life. With the demonstration of bioequivalence between subcutaneous and intravenous treprostinil, intravenous treprostinil may have an overall better risk-benefit profile than intravenous epoprostenol. OBJECTIVE: To evaluate the safety and efficacy of transitioning patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. METHODS: Patients enrolled in a 12-wk prospective open label study were switched from intravenous epoprostenol to intravenous treprostinil over 24 to 48 h. The intravenous treprostinil dose was adjusted to minimize symptoms/side effects. RESULTS: Thirty-one patients (mean age, 43 yr; 22 women) were enrolled. Twenty-seven patients completed the protocol; 4 patients transitioned back to epoprostenol. Six-minute walk distance (n = 27; baseline, 438 +/- 16 m; Week 12, 439 +/- 16 m), Naughton-Balke treadmill test time (n = 26; baseline, 582 +/- 50 s; Week 12, 622 +/- 48 s), functional class, and Borg score were maintained with intravenous treprostinil at Week 12 versus intravenous epoprostenol before transition. At Week 12, mean pulmonary artery pressure increased 4 +/- 1 mm Hg (n = 27, p < 0.01), cardiac index decreased 0.4 +/- 0.1 L/min/m2 (n = 27, p = 0.01), and pulmonary vascular resistance increased 3 +/- 1 Wood units x m2 (n = 26, p < 0.01). No serious adverse events were attributed to treprostinil. CONCLUSIONS: These data suggest that transition from intravenous epoprostenol to intravenous treprostinil is safe and effective; whether the hemodynamic differences associated with intravenous treprostinil are clinically important requires longer follow-up.

Adolescent↗
PubMed2005

Are we appropriately triaging patients with unstable angina?

BACKGROUND: It is uncertain how aggressively patients should be monitored and admitted to the hospital for chest pain syndromes and if the monitoring itself affects patient care, process, or outcomes. We assessed the appropriateness of care based on retrospective analysis of admission bed assignment (nonmonitored vs monitored) and Thrombolysis in Myocardial Infarction (TIMI) risk score in patients from the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. METHODS: Baseline characteristics, process of care, and outcomes were compared among 2939 patients admitted to 1 of 35 hospitals in the United States. Patients were stratified into low (0-2), intermediate (3 or 4), and high (5-7) risk based on TIMI risk score. RESULTS: Among the patients, 92 (3%) were admitted to the cardiac care unit (CCU), 1602 (56%) were admitted to the telemetry unit, and 1163 (41%) were admitted to an unmonitored bed. Paradoxically, high-risk patients comprised only 1% of those in the CCU, 5% of those in telemetry, and 10% of those in nonmonitored units. Conversely, low-risk patients were 64% of those in the CCU, 53% of those in telemetry, and 42% of those in unmonitored beds. Procedures were done more often on patients admitted to nonmonitored units than those on telemetry or in the CCU irrespective of TIMI risk score. CONCLUSIONS: This registry suggests that triage of patients does not routinely follow the risk-based approach suggested in the American College of Cardiology and American Heart Association guidelines and could therefore potentially lead to inefficiencies in care. Better implementation of risk stratification for acute coronary syndrome evaluation and management is necessary.

Aged↗
PubMed2005

Prostacyclin therapy for pulmonary arterial hypertension: new directions.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and smooth muscle cell proliferation of the pulmonary arterioles, as well as in situ thrombosis of the small pulmonary arteries. Prostacyclin is involved in PAH vascular remodeling. It is unclear if decreased prostacyclin in the lungs is a cause or a consequence of PAH, but the relative lack of prostacyclin and its positive effects on the pulmonary vascular bed support the theory that long-term prostacyclin replacement is effective. Current therapies based on evidence-based medicine include epoprostenol, treprostinil, iloprost, and beraprost, each with limitations based on the drugs' inherent properties and administration route. Treatment of PAH by inhibiting multiple pathways concurrently may produce additive benefit. Because prostacyclin therapy is not curative and does not normalize pulmonary hemodynamics in the majority of cases, combining a prostacyclin with other PAH agents may be a promising approach.

Antihypertensive Agents↗
PubMed2003

Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality.

The randomized, double-blind, placebo-controlled trial is the optimum method for clinical evaluation of new treatments, as assessed by clinicians and statisticians. However, if a known standard of therapy exists, it may be difficult to prove that a new therapy is superior. Equivalence and noninferiority clinical trial designs are now frequently utilized in clinical medical research. This article reviews the statistical differences between superiority, equivalence, and noninferiority design schemes, which pose specific ethical questions and have important implications for interpretation and clinical application of trial results. A guideline is proposed as a standard approach for reporting to facilitate qualitative assessment of the methodology of these trials.

Bias↗
PubMed2003

Statins and plaque stability.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are now the standard of care for patients with hypercholesterolaemia. This class of inhibitors, known as 'statins', has been shown to reduce cardiovascular morbidity and mortality. Accumulating data demonstrates a variety of mechanisms in which HMG-CoA reductase inhibition benefits the cardiovascular system. This review will discuss the pharmacology, clinical trials, and mechanisms, besides lipid lowering, of statin therapy.

Arteriosclerosis↗