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In one comparison from a 2-by-2 factorial trial, over 12,000 participants with a mean baseline blood pressure of 138/82 mm Hg were assigned to candesartan plus hydrochlorothiazide or to placebo. At 5.6 years, there was no between-group difference in the rates of cardiovascular events. High blood pressure is the leading risk factor for cardiovascular disease globally 1 and affects more than 1 billion adults worldwide. 2 Observational studies involving persons without cardiovascular disease show a graded increase in risk at systolic blood-pressure levels above 115 mm Hg. 3 It has been suggested that lowering blood pressure at any level above this value will reduce the risk of cardiovascular events. 4 Antihypertensive therapy has been clearly shown to reduce the risk of cardiovascular disease among people with vascular or renal disease, diabetes, or hypertension with end-organ damage or, in the absence of these conditions, among persons with a systolic . . .

In a 2-by-2 factorial trial, 12,705 persons at intermediate risk were assigned to candesartan plus hydrochlorothiazide or placebo and to rosuvastatin or placebo. At 5.6 years, combination therapy resulted in a significantly lower risk of cardiovascular events than dual placebo. Cardiovascular diseases are major causes of death and illness worldwide. 1 Both systolic blood pressure and low-density lipoprotein (LDL) cholesterol show graded associations with cardiovascular disease and together account for two thirds of the population-attributable risk of cardiovascular disease. 2 – 4 Therefore, combined lowering of LDL cholesterol and blood pressure can potentially have a bigger effect in reducing cardiovascular events than either intervention alone. Because the majority of cardiovascular events occur in persons at average risk with no previous cardiovascular disease, a strategy of broad population-based treatment of LDL cholesterol and blood pressure could be more effective than targeting only high-risk persons. . . .

Patients with high-grade atrioventricular block usually require the implantation of a permanent pacemaker. Retrospective studies have suggested that dual-chamber pacemakers reduce the risk of atrial fibrillation, stroke, heart failure, and death in this setting, as compared with single-chamber ventricular pacemakers. In a randomized trial comparing these two pacing methods, however, no significant advantage of dual-chamber pacing was demonstrated. In a randomized trial comparing these two pacing methods, no significant advantage of dual-chamber pacing was demonstrated. Cardiac pacing is the established treatment for high-grade atrioventricular block, but the appropriate pacing mode remains the subject of debate. 1 Single-chamber ventricular pacing prevents bradycardia and death from ventricular standstill, but dual-chamber pacing better emulates normal cardiac physiology by restoring atrioventricular synchrony and matching the ventricular pacing rate to the sinus rate. As a result, dual-chamber pacing, as compared with single-chamber ventricular pacing, improves hemodynamic function, 2 – 4 but the clinical benefit is uncertain. Nonrandomized studies suggest that dual-chamber pacing is associated with a lower incidence of atrial fibrillation, stroke, and heart failure than is single-chamber pacing. 5 There is also evidence . . .

The performance of emerging transcatheter aortic valve implantation (TAVI) clinical prediction models (CPMs) in national TAVI cohorts distinct from those where they have been derived is unknown. This study aimed to investigate the performance of the German Aortic Valve, FRANCE-2, OBSERVANT and American College of Cardiology (ACC) TAVI CPMs compared with the performance of historic cardiac CPMs such as the EuroSCORE and STS-PROM, in a large national TAVI registry. The calibration and discrimination of each CPM were analyzed in 6676 patients from the UK TAVI registry, as a whole cohort and across several subgroups. Strata included gender, diabetes status, access route, and valve type. Furthermore, the amount of agreement in risk classification between each of the considered CPMs was analyzed at an individual patient level. The observed 30-day mortality rate was 5.4%. In the whole cohort, the majority of CPMs over-estimated the risk of 30-day mortality, although the mean ACC score (5.2%) approximately matched the observed mortality rate. The areas under ROC curve were between 0.57 for OBSERVANT and 0.64 for ACC. Risk classification agreement was low across all models, with Fleiss's kappa values between 0.17 and 0.50. Although the FRANCE-2 and ACC models outperformed all other CPMs, the performance of current TAVI-CPMs was low when applied to an independent cohort of TAVI patients. Hence, TAVI specific CPMs need to be derived outside populations previously used for model derivation, either by adapting existing CPMs or developing new risk scores in large national registries.

A multicenter trial evaluated patients with previous anterior-wall myocardial infarction who were not candidates for an implantable cardioverter–defibrillator. Patients were randomly assigned either to have an automated external defibrillator (AED) at home for management of cardiac arrest or to receive standard treatment. At a median follow-up of 3 years, there was no significant difference between the two groups in mortality from any cause. Patients with previous anterior-wall myocardial infarction were randomly assigned either to have an automated external defibrillator (AED) at home for management of cardiac arrest or to receive standard treatment. At a median follow-up of 3 years, there was no significant difference between the two groups in mortality from any cause. Sudden cardiac arrest remains an unsolved public health problem, with approximately 166,200 out-of-hospital cardiac arrests occurring annually in the United States. 1 The use of automated external defibrillators (AEDs) by trained lay responders in community-based public-access defibrillation programs has been shown to increase survival after sudden cardiac arrest. However, what effect the use of the device has on overall mortality for the community at risk is unknown. 2 – 5 Particularly impressive results have been reported when sudden cardiac arrest is witnessed and an AED is immediately available, as on airplanes and in casinos and airports. 6 – 8 However, the effect of such programs . . .

Aortic stenosis (AS) is caused by age-related calcific degeneration of the aortic valve (1). Initially, cases are asymptomatic but, from the point that symptoms first develop, there is rapid progression and if left untreated survival estimates are low (2–3 years) (1). Therefore, managing AS effectively and efficiently is a priority for health systems with increasing healthcare costs and longer life expectancy.

In one comparison from a 2-by-2 factorial trial, 12,705 persons at intermediate cardiovascular risk were assigned to either rosuvastatin or placebo. At 5.6 years, there were significantly fewer participants with cardiovascular events in the rosuvastatin group than in the placebo group. Cardiovascular diseases cause 18 million deaths per year globally and a similar number of nonfatal cardiovascular events. 1 Elevated low-density lipoprotein (LDL) cholesterol levels account for approximately half the population-attributable risk of myocardial infarction 2 and approximately one quarter of the risk of ischemic stroke. 3 In previous trials, lowering LDL cholesterol levels with statins has been shown to reduce the risk of cardiovascular diseases, but most of the patients enrolled in those trials had vascular disease, elevated lipid levels, elevated inflammatory markers, hypertension, or diabetes. 4 , 5 The association between LDL cholesterol level and cardiovascular disease is graded and has no documented threshold. . . .

Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

Public access automatic external defibrillators (AEDs) can save lives, but most deaths from out-of-hospital sudden cardiac arrest occur at home. The Home Automatic External Defibrillator Trial (HAT) found no survival advantage for adding a home AED to cardiopulmonary resuscitation (CPR) training for 7,001 patients with a prior anterior wall myocardial infarction. Quality of life (QOL) outcomes for both the patient and spouse/companion were secondary end points. A subset of 1,007 study patients and their spouse/companions was randomly selected for ascertainment of QOL by structured interview at baseline and 12 and 24 months after enrollment. The primary QOL measures were the Medical Outcomes Study 36-Item Short-Form psychological well-being (reflecting anxiety and depression) and vitality (reflecting energy and fatigue) subscales. For patients and spouse/companions, the psychological well-being and vitality scales did not differ significantly between those randomly assigned an AED plus CPR training and controls who received CPR training only. None of the other QOL measures collected showed a clinically and statistically significant difference between treatment groups. Patients in the AED group were more likely to report being extremely or quite a bit reassured by their treatment assignment. Spouse/companions in the AED group reported being less often nervous about the possibility of using AED/CPR treatment than those in the CPR group. Adding access to a home AED to CPR training did not affect QOL either for patients with a prior anterior myocardial infarction or their spouse/companion but did provide more reassurance to the patients without increasing anxiety for spouse/companions.