Hot off the presses! Aug 15 Lancet

The Aug 15 issue of the Lancet is now up on Pubget (About Lancet): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Heart disease: breaking down barriers
  - Lancet 374(9689):501 (2009)
  
• Research and ethics in China
  - Lancet 374(9689):502 (2009)
  
• USAID: an agency without leader and direction
  - Lancet 374(9689):502 (2009)
  
• Time to lower treatment BP targets for hypertension?
  - Lancet 374(9689):503-504 (2009)
  
• Left atrial appendage occlusion in non-valvular atrial fibrillation
  - Lancet 374(9689):504-506 (2009)
  
• Albuminuria in heart failure: a CHARMing new risk factor?
  - Lancet 374(9689):506-508 (2009)
  
• Key issues for global cardiovascular medicine
  - Lancet 374(9689):508-510 (2009)
  
• Who is ineligible for warfarin in atrial fibrillation?
  - Lancet 374(9689):510-511 (2009)
  
• Insulin glargine and malignancy: an unwarranted alarm
  Pocock SJ Smeeth L - Lancet 374(9689):511-513 (2009)
  
• Treatments for nicotine addiction should be a top priority
  Pollock JD Koustova E Hoffman A Shurtleff D Volkow ND - Lancet 374(9689):513-514 (2009)
  
• Online social networks and wellbeing
  - Lancet 374(9689):514 (2009)
  
• Public health and peace building in Nepal
  - Lancet 374(9689):515-516 (2009)
  
• Statins, the cholesterol controversy, and preventive cardiology
  - Lancet 374(9689):517-518 (2009)
  
• Drugs for the heart
  - Lancet 374(9689):518 (2009)
  
• Heartfelt emotions
  - Lancet 374(9689):519-520 (2009)
  
• Insulin glargine and cancer: another side to the story?
  - Lancet 374(9689):521 (2009)
  
• Intensive glucose control and cardiovascular outcomes
  - Lancet 374(9689):522 (2009)
  
• Intensive glucose control and cardiovascular outcomes
  - Lancet 374(9689):522-523 (2009)
  
• Intensive glucose control and cardiovascular outcomes
  - Lancet 374(9689):523 (2009)
  
• Intensive glucose control and cardiovascular outcomes
  - Lancet 374(9689):523-524 (2009)
  
• Intensive glucose control and cardiovascular outcomes – Authors' reply
  - Lancet 374(9689):524 (2009)
  
• Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial
  - Lancet 374(9689):525-533 (2009)
  Background The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients. Methods In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00421863. Results Over a median follow-up of 2·0 years (IQR 1·93–2·03), systolic and diastolic blood pressure were reduced by a mean of 23·5/8·9 mm Hg (SD 10·6/7·0) in the usual-control group and by 27·3/10·4 mm Hg (11·0/7·5) in the tight-control group (between-group difference 3·8 mm Hg systolic [95% CI 2·4–5·2], p<0·0001; and 1·5 mm Hg diastolic [0·6–2·4]; p=0·041). The primary endpoint occurred in 82 of 483 patients (17·0%) in the usual-control group and in 55 of 484 patients (11·4%) of the tight-control group (odds ratio 0·63; 95% CI 0·43–0·91; p=0·013). A composite cardiovascular endpoint occurred in 52 (9·4%) patients in the usual-control group and in 27 (4·8%) in the tight-control group (hazard ratio 0·50, 95% CI 0·31–0·79; p=0·003). Side-effects were rare and did not differ significantly between the two groups. Interpretation Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension. Funding Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.
• Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
  - Lancet 374(9689):534-542 (2009)
  Background In patients with non-valvular atrial fibrillation, embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. We assessed the efficacy and safety of percutaneous closure of the LAA for prevention of stroke compared with warfarin treatment in patients with atrial fibrillation. Methods Adult patients with non-valvular atrial fibrillation were eligible for inclusion in this multicentre, randomised non-inferiority trial if they had at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes, hypertension, or were 75 years or older. 707 eligible patients were randomly assigned in a 2:1 ratio by computer-generated randomisation sequence to percutaneous closure of the LAA and subsequent discontinuation of warfarin (intervention; n=463) or to warfarin treatment with a target international normalised ratio between 2·0 and 3·0 (control; n=244). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolism. We selected a one-sided probability criterion of non-inferiority for the intervention of at least 97·5%, by use of a two-fold non-inferiority margin. Serious adverse events that constituted the primary endpoint for safety included major bleeding, pericardial ef! fusion, and device embolisation. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00129545. Findings At 1065 patient-years of follow-up, the primary efficacy event rate was 3·0 per 100 patient-years (95% credible interval [CrI] 1·9–4·5) in the intervention group and 4·9 per 100 patient-years (2·8–7·1) in the control group (rate ratio [RR] 0·62, 95% CrI 0·35–1·25). The probability of non-inferiority of the intervention was more than 99·9%. Primary safety events were more frequent in the intervention group than in the control group (7·4 per 100 patient-years, 95% CrI 5·5–9·7, vs 4·4 per 100 patient-years, 95% CrI 2·5–6·7; RR 1·69, 1·01–3·19). Interpretation The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation. Funding Atritech.
• Albuminuria in chronic heart failure: prevalence and prognostic importance
  - Lancet 374(9689):543-550 (2009)
  Background Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. Methods UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study—ie, death from cardiovascular causes or admission to hospital with worsening heart failure—and death from any cause were assessed. Findings 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1·43 (95% CI 1·21–1·69; p<0·0001) and for macroalbuminuria versus normoalbuminuria was 1·75 (1·39–2·20; p<0·0001). The a! djusted values for death were 1·62 (1·32–1·99; p<0·0001) for microalbuminuria versus normoalbuminuria, and 1·76 (1·32–2·35; p=0·0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. Interpretation Increased UACR is a powerful and independent predictor of prognosis in heart failure. Funding AstraZeneca.
• Hypoplastic left heart syndrome
  - Lancet 374(9689):551-564 (2009)
  Hypoplastic left heart syndrome is a rare congenital heart defect in which the left side of the heart is underdeveloped. Surgical management of hypoplastic left heart syndrome has changed the prognosis of the condition that was previously regarded as fatal. We discuss surgical strategies based on staged procedures, with the right ventricle supporting both systemic and pulmonary circulation. We also discuss other management options, such as neonatal transplantation and the recent innovation of hybrid techniques. Surgical techniques and the understanding of the pathophysiology of this condition have been at the forefront of neonatal cardiac surgery and intensive care. The management of the syndrome remains a challenge because affected children grow into adolescence and adulthood posing various new problems and demands.
• Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends
  - Lancet 374(9689):565-576 (2009)
  Over 4 million people worldwide have received a prosthetic heart valve, and an estimated 300 000 valves are being implanted every year. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges for clinicians and patients. Here, we review antithrombotic therapies for patients with prosthetic heart valves and management of thromboembolic complications. Advances in antithrombotic therapy and valve technologies are likely to improve the management of patients with prosthetic heart valves in developed countries, but the most important unmet need and potential for benefit from these new therapies is in developing countries where a massive and rapidly increasing burden of valvular heart disease exists.
• Drug-induced fibrotic valvular heart disease
  - Lancet 374(9689):577-585 (2009)
  The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. ! Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.
• Beans in the pericardium
  - Lancet 374(9689):586 (2009)