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

Association of hemoglobin levels with clinical outcomes in acute coronary syndromes.

BACKGROUND: In the setting of an acute coronary syndrome (ACS), anemia has the potential to worsen myocardial ischemia; however, data relating anemia to clinical outcomes in ACS remain limited. METHODS AND RESULTS: We examined the association between baseline hemoglobin values and major adverse cardiovascular events through 30 days in 39,922 patients enrolled in clinical trials of ACS. After adjustment for differences in baseline characteristics and index hospitalization treatments, a reverse J-shaped relationship between baseline hemoglobin values and major adverse cardiovascular events was observed. In patients with ST-elevation myocardial infarction, when those with hemoglobin values between 14 and 15 g/dL were used as the reference, cardiovascular mortality increased as hemoglobin levels fell below 14 g/dL, with an adjusted OR of 1.21 (95% CI 1.12 to 1.30, P<0.001) for each 1-g/dL decrement in hemoglobin. At the other end of the range of hemoglobin, patients with hemoglobin values >17 g/dL also had excess mortality (OR 1.79, 95% CI 1.18 to 2.71, P=0.007). In patients with non-ST-elevation ACS, with those with hemoglobin 15 to 16 g/dL used as the reference, the likelihood of cardiovascular death, myocardial infarction, or recurrent ischemia increased as the hemoglobin fell below 11 g/dL, with an adjusted OR of 1.45 (95% CI 1.33 to 1.58, P<0.001) for each 1 g/dL decrement in hemoglobin. Patients with hemoglobin values >16 g/dL also had an increased rate of death or ischemic events (OR 1.31, 95% CI 1.03 to 1.66, P=0.027). CONCLUSIONS: Anemia is a powerful and independent predictor of major adverse cardiovascular events in patients across the spectrum of ACS.

Interleukin-18 and interleukin-18 binding protein levels before and after percutaneous coronary intervention in patients with and without recent myocardial infarction.

Serum levels of interleukin-18 (IL-18) and its endogenous antagonist IL-18 binding protein were measured in 84 patients before and after coronary angioplasty. Patients who had high levels of troponin I immediately before angioplasty were considered to have experienced a "recent" myocardial infarction. Concentrations of IL-18 (355 vs 316 pg/ml) and ratio of IL-18 to IL-18 binding protein (107 vs 69) were significantly higher among patients who had recent myocardial infarction than among those who did not, indicating a relation between unopposed IL-18 activity and recent myocardial infarction.

Anemia and its relationship to clinical outcome in heart failure.

BACKGROUND: Anemia is often observed in patients with chronic heart failure (CHF), but its implications for patient outcomes are not well understood. The goal of this study was to investigate the relationship between anemia, severity of CHF, and clinical outcomes. METHODS AND RESULTS: Hemoglobin concentration (Hb) was measured in 912 subjects with CHF enrolled in the Randomized Etanercept North American Strategy to Study Antagonism of Cytokines (RENAISSANCE) trial. In a subgroup of 69 subjects, cardiac MRI was performed at randomization and 24 weeks later. Anemia (Hb < or =12.0 g/dL) was present in 12% of subjects. Cox regression analysis indicated that for every 1-g/dL-higher baseline Hb, the risk of mortality was 15.8% lower (P=0.0009) and the risk of mortality or hospitalization for heart failure was 14.2% lower (P<0.0001). Greater CHF severity was associated with significantly lower Hb concentrations. An increase in Hb over time was associated with a decrease in left ventricular mass and lower mortality, whereas a decrease in Hb over time was associated with an increase in left ventricular mass and higher mortality. In multivariate analysis, anemia remained a significant, independent predictor of death or hospitalization for heart failure, with both outcomes being significantly higher in all NYHA classes. CONCLUSIONS: Anemia is frequently present in patients with CHF. Lower Hb is associated with greater disease severity, a greater left ventricular mass index, and higher hospitalization and mortality rates.

Anti-inflammatory strategies in coronary atherosclerosis.

Recent evidence has demonstrated that inflammation plays an important role in the progression of coronary atherosclerosis. This review focuses on acute coronary syndromes and examines some novel therapeutic strategies aimed at manipulating the inflammatory environment in these patients in order to reduce the subsequent major adverse coronary event rate following myocardial infarction.