The effects of initiation or continuation of statin therapy on cholesterol level and all-cause mortality after the diagnosis of left ventricular systolic dysfunction.

BACKGROUND: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) are known to reduce mortality and cardiac events in patients with coronary artery disease who have not progressed to left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). This study investigated the effect of changes in statin therapy and cholesterol level on mortality in patients with LVSD. METHODS: Data from consecutive patients with LVSD enrolled in a single local hospital HF management program were analyzed. Patients were grouped according to changes in statin treatment within 4 months after their initial visit: groups NS (no statin), IS (initiation of statin), CS (continuation of statin), and SS (statin stopped). RESULTS: Nine hundred patients were followed for a median of 36 (28-43) months (range, 16-66 months). The 2-year mortality was 16.7%. Groups IS and CS had lower 2-year mortality than groups NS and SS (11.0% and 11.9% vs 22.0% and 34.8%, respectively; P < .001). This was independent of age, sex, severity of LVSD, HF medications, New York Heart Association functional class, and baseline cholesterol. The effect was mainly observed in patients with coronary artery disease. In 734 patients who had completed 1-year follow-up on stable HF treatment, neither baseline cholesterol nor change over 1 year predicted outcome. CONCLUSION: Initiation and maintenance of treatment with statins is associated with better survival in patients with LVSD. This could not be explained by other measured variables.

Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.

Anemia, renal dysfunction, and their interaction in patients with chronic heart failure.

Anemia and renal dysfunction (RD) are frequent complications seen in chronic heart failure (HF). However, the prevalence and interaction of these co-morbidities in a representative population of outpatients with chronic HF is poorly described. In this study, it was sought to determine the association between RD and anemia in patients with HF enrolled in a community-based HF program. Nine hundred fifty-five patients with HF due to left ventricular systolic dysfunction were investigated for the prevalence of anemia and its cause and followed for a median of 531 days. Anemia was defined as hemoglobin < 12.0 g/dl in women and < 13.0 g/dl in men. RD was defined as a calculated glomerular filtration rate of < 60 ml/min. The prevalence of anemia was 32%. Fifty-three percent of patients with and 27% of those without anemia had > or = 1 test suggesting hematinic deficiency. The prevalence of RD was 54%. Forty-one percent of patients with and 22% of patients without RD had anemia, with similar proportions associated with iron deficiency in the presence or absence of RD. Anemia and RD independently predicted a worse outcome, and this effect was additive. In conclusion, in outpatients with chronic HF, anemia and RD are common and co-exist but confer independent prognostic information. A deficiency of conventional hematinic factors may cause about 1/3 of anemia in this clinical setting.

Clinical trials update from the American College of Cardiology meeting: CARE-HF and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF, VERITAS, CANPAP, PEECH and PREMIER.

This article provides information and a commentary on landmark trials presented at the American College of Cardiology meeting held in March 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. CARE-HF showed that Cardiac Re-synchronisation Therapy, administered in addition to expert pharmacological management, reduced all cause mortality and CV hospitalisation in patients with moderate or severe heart failure and cardiac dyssynchrony. The Women's Health Study showed no benefit of vitamin E supplementation or aspirin in the primary prevention of CV disease. The TNT study showed that reducing LDL cholesterol to levels lower than currently recommended, produced a 22% reduction in the incidence of major cardiovascular events. In COMPASS, an implantable device that continuously monitors intra-cardiac pressures was shown to be safe and to improve care in patients with chronic heart failure. Tezosentan failed to show benefit in patients with acute heart failure in the VERITAS study. The CANPAP study failed to show a benefit of continuous positive airway pressure on mortality and heart transplantation in heart failure patients with central sleep apnoea. EECP therapy improved exercise capacity but had no effect on peak VO2 in heart failure patients in the PEECH study. In the PREMIER study the matrix metalloproteinase inhibitor PG-116800 failed to prevent LV remodelling following myocardial infarction.

Once-monthly administration of darbepoetin alfa for the treatment of patients with chronic heart failure and anemia: a pharmacokinetic and pharmacodynamic investigation.

In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin

Hypertension, left ventricular hypertrophy, and sudden death.

Left ventricular hypertrophy (LVH), a form of end-organ damage in hypertension, is associated with increased incidence of sudden cardiac death (SCD). This review explores the possible mechanisms behind this phenomenon. SCD in LVH could be thrombotic/ischemic or arrhythmic (eg, myocardial ischemia, even in the absence of significant coronary artery disease, may be one important factor). Abnormalities of flow-mediated dilatation, endothelial function, and a hypercoagulable state are well-observed abnormalities in association with hypertension and LVH, although their precise contributory role is as yet undefined in the pathogenesis of sudden death. Electrophysiologic abnormalities are also well documented in LVH, and such patients are more predisposed to arrhythmias. In the past decade, many studies have investigated the regression of LVH, and recent studies are addressing whether the latter translates into a prognostic benefit.