Claire Braybrook

Endovascular versus open repair for abdominal aortic aneurysm: EVAR trial 1

of 956 calcified plaques were identified in a group of 217 participants with detectable coronary artery calcium. The calcium concentration, Agatston score, calcified volume and mineral mass of individual plaques was measured in each subject. Subsequent data analysis revealed that calcium concentrations of plaques were independent of the patient’s age and sex, and were associated with the stage of plaque formation. Among a subgroup of 125 subjects with multiple (≥3) calcified plaques, calcium concentration was heterogeneous within subjects, and the degree of heterogeneity was independent of age, sex and plaque number. If confirmed in larger studies, these findings indicate that calcium concentration measurements for individual calcified plaques could be a useful additional marker to global scores in the assessment of plaque burden and coronary event risk. Claire Braybrook

US phase I trial of the Amplatzer ® Membranous VSD Occluder

address the lack of reliable outcome data for self-management provided by individual trials, Heneghan and colleagues used meta-analysis to compare standard monitoring of oral anticoagulation with self-management (self-testing and self-dosage). Fourteen randomized controlled trials comparing the effects of self-monitoring with those of standard monitoring by a healthcare service or physician over 2–24 months were included; four trials were considered to be of low quality but were still included. Analysis showed that self-monitoring more than halved the risk of thromboembolic events (odds ratio 0.41, 95% CI 0.25–0.70; P = 0.001) and reduced the risk of major hemorrhage by one-third (odds ratio 0.66, 95% CI 0.37–0.16; P = 0.15) compared with standard monitoring. Pooled analysis of the 10 trials that recorded information on death showed that selfmonitoring was associated with reduced all-cause mortality (odds ratio 0.58, 95% CI 0.36–0.95; P = 0.03). All 11 studies that recorded INRs reported improvements in the self-monitoring groups compared with the standard-monitoring groups. Compared with patients managed by standard methods, those who both self-monitored and selfadjusted the doses were at reduced risk of mortality and thromboembolic events, but at increased risk of hemorrhage. The results of this combined analysis show that self-monitoring improves the success of oral anticoagulation therapy by reducing the risk of adverse events and improving the ability to maintain the INR in the therapeutic range. Kate Matthews

Pulmonary artery catheter use in advanced heart failure: the ESCAPE trial

hypotension, and the clip partially detached from the mitral leaflets in three individuals. Following therapy, a sustained reduction in mitral regurgitation was observed in most patients over 6 months. This study has shown that use of a metal clip device for edge-to-edge percutaneous mitral valve repair is safe and technically feasible, and can also lessen symptoms of mitral regurgitation. Although the authors acknowledge that the technique does not seem to prevent mitral regurgitation in all patients, the promising results have led to further evaluation of its risks and benefits in a phase II randomized trial. Claire Braybrook

Fasudil as an adjunctive therapy for patients with stable angina

Phosphodiesterase type 5 (PDE5) metabolizes cyclic guanosine monophosphate, a SECOND MESSENGER that mediates the vaso dilatory effects of nitric oxide. In patients with pulmonary arterial hypertension (PAH), PDE5 is up regulated, contributing to increased pulmonary vascular resistance, right ventricular failure and eventually death. Following encouraging results from preliminary studies, Galiè et al. conducted a multicenter, placebocontrolled trial investigating the efficacy and safety of sildenafil—a PDE5 inhibitor—in patients with PAH. Patients (n = 278) were randomized in a 1:1:1:1 pattern to receive placebo or 20, 40 or 80 mg sildenafil three times daily. The primary efficacy measure was the change in exercise capacity from baseline to week 12 on 6-min walking test—an independent predictor of death in patients with idiopathic PAH. Other measures included mean pulmonary artery pressure change and time to clinical worsening. Patients receiving sildenafil showed increased 6-min walking distances at weeks 4, 8 and 12 (P <0.001 for all doses). Sildenafil significantly decreased mean pulmonary artery pressure (P = 0.04, P = 0.01 and P <0.001 for 20, 40 and 60 mg sildenafil, respectively). No significant difference was seen in time to clinical worsening with sildenafil compared with placebo. Most adverse events were mild to moderate in intensity for all groups and, although three of the four patients who died were in the sildenafil group, no deaths were considered to be related to study treatment. The authors conclude that sildenafil treatment safely improves exercise capacity and decreases pulmonary artery pressure in patients with PAH. As no dose response was found, 20 mg of sildenafil might completely inhibit PDE5. Rebecca Ireland

Elevated levels of tumor markers in heart failure patients

risk of restenosis in patients who are allergic to nickel. The single-blind, randomized, prospective, TiNOX study was performed at centers in Switzerland and Germany, and compared the safety and efficacy of stents coated with titanium oxynitride (TiNOX) with that of uncoated stainless steel stents in patients with de novo, native coronary artery lesions. Patients were randomly assigned TiNOX stents (n = 45) or bare (stainless steel) stents (n = 47; control). After 6 months of follow-up, coronary angiography showed that late loss, a measure of neointimal hyperplasia, was significantly lower in lesions treated with TiNOX stents than in those treated with control stents (P = 0.03). The TiNOX group showed decreased percent diameter sten osis compared with the control group (P = 0.04). A lower number of target lesion revascularizations were performed in the TiNOX group than in the control group, which resulted in significantly fewer major adverse cardiac events in the TiNOX group (P = 0.02). The authors conclude that revascularization with TiNOX stents is safe and effective in patients with de novo native coronary artery lesions. Limitations of the trial are discussed, and the authors make suggestions for future studies using TiNOX stents, including modifications of stent design and comparison with drug-eluting stents. Rebecca Ireland

Should more patients with ischemic stroke be eligible for tPA treatment

were compared with patients in permanent AF in the rate-control group (n = 178). The primary endpoint was a composite of cardiovascular death, heart failure, thromboembolic complications, bleeding, severe adverse effects from use of antiarrhythmics, and pacemaker implantation. Quality of life was assessed at baseline, 12 months, and at study end (30 or 36 months). No statistically significant difference was seen in the rates of occurrence of the primary endpoint between the two groups (22% in the rhythm-control group vs 15% in the ratecontrol group). Maintenance of long-term sinus rhythm was not associated with event-free survival; regression analyses identified coronary artery disease, previous bleeding, limited exercise tolerance and digitalis use as being independent risk indicators. No differences between groups were seen in quality-of-life measures. While acknowledging limitations of their study, the authors conclude that effective rhythm control did not improve survival, and that associated cardiovascular disease was a much more important cause of major cardiovascular events than arrhythmias. They state that diagnosis and treatment of AF should initially focus on the conditions linked to AF, and insist on the need for further studies to identify safer and more-effective AF treatments. Rebecca Ireland

Repair versus replacement of mitral valves in patients with infective endocarditis

receiving placebo died by day 13 (one before surgery) compared with five receiving amiodarone. Amiodarone was associated with fewer postoperative sustained ventricular tachyarrhythmias and slightly shorter hospital stay than placebo; it also produced few adverse effects and no serious postoperative events over 1 year of follow-up, although ventricular response rate was slower in this group. These positive results oppose previous reports that amiodarone is effective only in certain subgroups of patients. According to the authors, delaying surgery to accommodate 6 days’ preoperative amiodarone administration to allow the treatment to take effect might be warranted. Pippa Murdie

MMP-9: a new therapeutic target for preventing plaque rupture?

lower among individuals who ate more than five servings per day. In developed countries, although current recommendations advocate at least five servings daily, the average daily consumption of fruit and vegetables is only about three servings. Results from this study provide strong support for raising the number of portions consumed, which could substantially reduce stroke morbidity and mortality. Claire Braybrook

Safety and feasibility of edge-to-edge mitral valve repair: the EVEREST trial

levels. Study participants were randomized to receive 400 mg bezafibrate (n = 178) or placebo (n = 161) once daily. After a median of 6.3 years, diabetes developed in 37.0% of patients from the placebo group and 27.1% of patients from the bezafibrate group (log rank analysis = 0.01). The onset of diabetes was significantly delayed in bezafibrate-treated patients (median 4 years, interquartile range 2.1–5.0) compared with placebo-treated patients (median 2 years, interquartile range 0.5–3.5; P = 0.002). Multivariate analysis showed that bezafibrate treatment was an independent predictor of reduced risk of developing type 2 diabetes ( hazard ratio 0.59, 95% CI 0.39–0.91). Pharmacologic intervention using bezafibrate, which influences primary lipid metabolism, was thereby shown to delay the time to onset and decrease the incidence of type 2 diabetes in obese patients with normal fasting glucose levels. The authors urge caution, however, in interpreting their findings, as the development of diabetes was not declared an endpoint of the original study, but was identified by subsequent obesity analysis. In addition, use of impaired fasting glucose to diagnose diabetes at baseline could have been inaccurate; glucose tolerance tests should also have been used. Kate Matthews

Potential of skeletal myoblast transplantation for ischemic heart disease

levels. Study participants were randomized to receive 400 mg bezafibrate (n = 178) or placebo (n = 161) once daily. After a median of 6.3 years, diabetes developed in 37.0% of patients from the placebo group and 27.1% of patients from the bezafibrate group (log rank analysis = 0.01). The onset of diabetes was significantly delayed in bezafibrate-treated patients (median 4 years, interquartile range 2.1–5.0) compared with placebo-treated patients (median 2 years, interquartile range 0.5–3.5; P = 0.002). Multivariate analysis showed that bezafibrate treatment was an independent predictor of reduced risk of developing type 2 diabetes ( hazard ratio 0.59, 95% CI 0.39–0.91). Pharmacologic intervention using bezafibrate, which influences primary lipid metabolism, was thereby shown to delay the time to onset and decrease the incidence of type 2 diabetes in obese patients with normal fasting glucose levels. The authors urge caution, however, in interpreting their findings, as the development of diabetes was not declared an endpoint of the original study, but was identified by subsequent obesity analysis. In addition, use of impaired fasting glucose to diagnose diabetes at baseline could have been inaccurate; glucose tolerance tests should also have been used. Kate Matthews