Impact of a Standardized Titration Protocol with Carvedilol in Heart Failure: Safety,Tolerability, and Efficacy—A Report from the GESICA Registry

Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) studied whether a standardized protocol for the initiation and titration of the β-blocker carvedilol in a multicenter, open-label program would optimize β-blocker use in heart failure (HF) patients. The program included: (1) the carvedilol initiation and titration period, and (2) long-term follow-up at 6 and 12 months. Of 1299 patients in the registry, 504 were excluded due to current therapy; of the remaining 795 eligible patients, 293 were excluded due to contraindications. Of the included patients with follow-up data (n = 316), 93.3% tolerated carvedilol initiation and 47.7% of the patients reached the target dose of 50 mg/day for a mean dose of 39 mg/day. Rates were comparable in the elderly (n = 83), of which 53% achieved a target dose for a mean dose of 43.08 mg/day. This protocol improved therapy rates and achieved target doses quickly (average of 4 visits). Concomitant medications did not have to be adjusted and there were low withdrawal rates (10%) and hospital admissions (7.2%) for HF. Patients were able to maintain carvedilol therapy at 6 and 12 months. These results indicate that a standardized titration protocol, as used in GESICA, for the initiation and titration of β-blockers is well tolerated and may improve β-blocker use in carefully selected heart failure patients.The study authors are members of the GESICA Steering Committee and Subcommittees     

The involvement of the renin-angiotensin system gene polymorphisms in coronary heart disease

INTRODUCTION AND OBJECTIVES: Previous studies angiotensin-converting enzyme gene insertion/deletion polymorphism ACE (I/D), angiotensinogen gene polymorphism, and angiotensin II AT1 receptor polymorphism in relation to coronary heart disease controversial results. This study was designed to analyze the association between these gene polymorphisms and the first coronary event in individuals residing on Grand Canary Island, Spain. PATIENTS AND METHOD: Case-control study. Case subjects (n = 304) were recruited at the first coronary event; age-matched controls (n = 315) were randomly selected from the Grand Canary population. Participants were examined for the usual risk factors. Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by PCR and restriction analysis. RESULTS: Neither ACE (I/D) nor AT1 receptor polymorphism was associated with coronary heart disease, whereas the frequency distribution of AGT M235T genotypes among patients and control subjects (TT: 29% and 19%; MT: 48% and 50%; MM: 22% and 31%, respectively) was statistically different (p = 0.003). Multiple logistic regression analysis identified the TT genotype of the angiotensinogen gene (OR = 1.9; 95% CI 1.1-3.4), diabetes (OR = 4.4; 95% CI 2.0-9.4) and hypertension (OR = 2.1; 95% CI 1.3-3.3) as risk factors predicting the coronary event. CONCLUSIONS: Our results provide no evidence of an association between ACE (I/D) or AT1 receptor polymorphism and coronary heart disease. However, homozygosity for the T allele of the angiotensinogen gene, diabetes and hypertension independently place individuals at higher risk of experiencing a coronary event on Grand Canary Island.     

Increased risk of tuberculosis in patients with rheumatoid arthritis

OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.     

Factors associated with poor outcomes in patients with lupus nephritis

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.     

Impact of physician specialty on the cost of nonvariceal upper GI bleeding care

OBJECTIVE: Upper GI bleeding (UGIB) is a common medical emergency that leads to a high consumption of medical resources and costs. We aimed to analyze the influence of physician specialty on the costs of nonvariceal UGIB care. METHODS: We retrospectively assessed 350 nonvariceal UGIB episodes that were primarily cared for by gastroenterologists (n = 142), internists (n = 67), or surgeons (n = 141). Gastroenterologists followed evidence-based clinical protocols that included early endoscopy and early hospital discharge for uncomplicated bleeding. A risk score system was used to control for severity of illness. Linear regression analyses were performed to find out predictors of costs and the influence of specialist care on length of stay (LOS). RESULTS: The overall mean hospital cost was significantly lower in patients cared for by gastroenterologists (EUR 1,630) than in those managed by internists (EUR 3,745, p < 0.001) or surgeons (EUR 2,513, p < 0.05). The mean LOS was the variable with highest influence on total cost. Patients cared for by gastroenterologists had a mean LOS significantly shorter (7.3 days) than that of those treated by internists (16.2 days, p < 0.001) or surgeons (11 days, p < 0.001). Hospital costs and LOS differences were maintained when adjusting for severity of illness. In caring for low risk patients, nongastroenterologists had a higher probability of having a hospital stay longer than 4 days (odds ratio = 18.4, Cl = 4.6-73.6, p < 0.001). CONCLUSION: The implementation of specific evidence-based protocols by gastroenterologists reduces length of hospital stay and saves medical costs in patients with nonvariceal UGIB, especially those at low risk.     

Seasonal variations in admissions for acute myocardial infarction. The PRIMVAC study

INTRODUCTION AND OBJECTIVES: Some authors have described seasonal variations in the incidence of acute myocardial infarction. The aim of this study was to determine the existence of seasonal rhythms in admissions for acute myocardial infarction to coronary care units, and in mortality, and to analyze the influence of age on environmental factors. PATIENTS AND METHOD: The study included a total of 8400 consecutive patients with acute myocardial infarction admitted to 12 coronary care units in the PRIMVAC registry from January 1995 to December 1999. Seasonal rhythms were analyzed with the time series method and the Cosinor regression equation. The influence of age was analyzed with the chi 2 test. RESULTS: The total number of admissions increased in winter and decreased in summer. The highest peak (acrophase) occurred in winter, with 2183 cases (r2=0.91), specifically in February, with 742 cases (r2=0.66). The age of the patients conditioned seasonal variations (P=.006), and the influence was statistically significant for patients over 65 years of age. Changes in mortality with time did not reach statistical significance. CONCLUSIONS: A seasonal rhythm in admissions for acute myocardial infarction was found, with an increase in winter and a decrease in summer. Age conditioned the effect of environmental factors on acute myocardial infarction, and patients aged 65 years or older were more sensitive to mechanisms that led to increases in admissions in winter.     

Predictors and implications of residual plaque burden after coronary stenting: an intravascular ultrasound study

Background Residual plaque burden after coronary stenting may be visualized by use of intravascular ultrasound. Determinants and implications of residual atherosclerotic plaque burden after coronary stenting are not well established. In particular, the implications of residual plaque burden, after adjusting for confounding factors, are still unknown. Methods Sixty-two consecutive patients (age 56 ± 9 years) undergoing coronary stenting under intravascular ultrasound imaging guidance were prospectively studied. A total of 616 slices were analyzed (every 2 mm of stent length) from motorized pull-back recordings. Residual plaque burden was calculated as residual plaque/vessel area × 100. Results In 565 slices (89%), both residual plaque area and stent area could be measured. Mean residual plaque burden was 46.5% ± 6%. By use of multiple regression analysis, lesion plaque area and reference segment plaque burden were identified as independent predictors of residual plaque burden after stenting. In addition, a significant correlation was found between residual plaque burden and most relevant angiographic parameters at follow-up (including minimal lumen diameter, percent diameter stenosis, and loss index), which persisted after adjustment. Furthermore, stents with a residual plaque burden ≥46% had higher a restenosis rate (relative risk [RR] 4.4, 95% CI 1.09-18.2, P = .03). On logistic regression analysis, residual plaque burden (RR 4.8, 95% CI 4.1-5.6, P = .01) and diabetes (RR 4.3, 95% CI 3.6-5.1, P = .03) emerged as the only independent predictors of restenosis. Conclusions The amount of residual plaque burden after coronary stenting plays an independent role on the late angiographic outcome of these patients. (Am Heart J 2003;145:254-61.)