Nic J. G. M. Veeger

Effect of Moderate or Intensive Disease Management Program on Outcome in Patients With Heart Failure: Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH)

BACKGROUND Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.

Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. a retrospective study of 2300 consecutive patients with venous thromboembolism

The efficacy and safety of vitamin K antagonists (VKA) are related to the actual level of anticoagulation (given as the international normalized ratio, INR). It is often difficult to maintain an optimal INR over time. We assessed the clinical impact of the individual time spent within INR target range (ITTR) in 2304 consecutive patients with venous thromboembolism. Annual incidences of recurrent thromboembolism and major bleeding were 6·2% and 2·8% respectively. The relative risk (RR) of thromboembolism was 4·5 [95% confidence interval (CI) 3·1–6·6, P < 0·001] at INR < 2·0, for major bleeding it was 6·4 (2·5–16·1, P < 0·001) at INR > 5·0, compared with INR 2·0–3·0. Patients with ITTR < 45% were at higher risk than those with ITTR > 65% (RR 2·8, 1·9–4·3, P < 0·001), while no difference was demonstrated comparing ITTR 45–65% and ITTR > 65% (RR 1·2, 0·7–1·8, P = 0·54). Annual incidences of recurrent thromboembolism were 16·0%, 4·9% and 4·6% at ITTR < 45%, 45–60% and >65% respectively. For major bleeding these were 8·7%, 2·1% and 1·9% respectively. ITTR < 37% during the first 30 treatment days was highly predictive for the total treatment time ITTR < 45% (RR 24·2, 13·5–43·1, P < 0·001). In conclusion, ITTR can be used to identify patients on VKA at risk of recurrent thromboembolism or major bleeding. Since the 30‐d ITTR is highly predictive for total treatment ITTR, these patients can be identified soon after start of treatment.

Design and methodology of the COACH study: a multicenter randomised Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure.

While there are data to support the use of comprehensive non‐pharmacological intervention programs in patients with heart failure (HF), other studies have not confirmed these positive findings. Substantial differences in the type and intensity of disease management programs make it impossible to draw definitive conclusions about the effectiveness, optimal timing and frequency of interventions.

Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives

Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.

High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome Results From a Large Retrospective Cohort Study

Background— No data are available on the absolute risk of either venous thromboembolism (VTE) or arterial thromboembolism (ATE) in patients with nephrotic syndrome. Reported risks are based on multiple case reports and small studies with mostly short-term follow-up. We assessed the absolute risk of VTE and ATE in a large, single-center, retrospective cohort study and attempted to identify predictive factors in these patients. Methods and Results— A total of 298 consecutive patients with nephrotic syndrome (59% men; mean age, 42±18 years) were enrolled. Mean follow-up was 10±9 years. Nephrotic syndrome was defined by proteinuria ≥3.5 g/d, and patients were classified according to underlying histological lesions accounting for nephrotic syndrome. Objectively verified symptomatic thromboembolic events were the primary study outcome. Annual incidences of VTE and ATE were 1.02% (95% confidence interval, 0.68 to 1.46) and 1.48% (95% confidence interval, 1.07 to 1.99), respectively. Over the first 6 months of follow-up, these rates were 9.85% and 5.52%, respectively. Proteinuria and serum albumin levels tended to be related to VTE; however, only the predictive value of the ratio of proteinuria to serum albumin was significant (hazard ratio, 5.6; 95% confidence interval, 1.2 to 26.2; P=0.03). In contrast, neither the degree of proteinuria nor serum albumin levels were related to ATE. Sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate predicted ATE (P≤0.02). Conclusions— This study verifies high absolute risks of symptomatic VTE and ATE that were remarkably elevated within the first 6 months. Whereas the ratio of proteinuria to serum albumin predicted VTE, estimated glomerular filtration rate and multiple classic risk factors for atherosclerosis were predictors of ATE.

Microalbuminuria and Risk of Venous Thromboembolism

CONTEXT Microalbuminuria (albuminuria 30-300 mg per 24-hour urine collection) is a well-known risk marker for arterial thromboembolism. It is assumed that microalbuminuria reflects generalized endothelial dysfunction. Hence, microalbuminuria may also predispose for venous thromboembolism (VTE). OBJECTIVE To assess whether microalbuminuria is associated with VTE. DESIGN, SETTING, AND PARTICIPANTS Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. All inhabitants of Groningen, The Netherlands, aged 28 through 75 years (n = 85,421) were sent a postal questionnaire and a vial to collect a first morning urine sample for measurement of urinary albumin concentration. Of those who responded (40,856), a cohort (8592 participants) including more participants with higher levels of urinary albumin concentration completed screening at an outpatient clinic. Screening data were collected on urinary albumin excretion (UAE) and risk factors for cardiovascular and renal disease. MAIN OUTCOME MEASURE Symptomatic and objectively verified VTE (ie, deep vein thrombosis, pulmonary embolism, or both) between study initiation and June 1, 2007. RESULTS Of 8574 evaluable participants (mean [SD] age, 49 [13] years; 50% men), 129 experienced VTE during a mean (SD) follow-up period of 8.6 (1.8) years, corresponding to overall annual incidence of 0.14% (95% confidence interval [CI], 0.11%-0.19%). Annual incidences were 0.12%, 0.20%, 0.40%, and 0.56% in participants with UAE of less than 15 (n = 6013), 15-29 (n = 1283), 30-300 (n = 1144), and greater than 300 (n = 134) mg per 24-hour urine collection, respectively (P for trend <.001). When adjusted for age, cancer, use of oral contraceptives, and atherosclerosis risk factors, hazard ratios associated with UAE levels of 15-29, 30-300, and greater than 300 mg/24 h were 1.40 (95% CI, 0.86-2.35), 2.20 (95% CI, 1.44-3.36), and 2.82 (95% CI, 1.21-6.61), respectively, compared with participants with UAE of less than 15 mg/24 h (global P = .001). Adjusted hazard ratio for microalbuminuria vs normoalbuminuria (UAE <30 mg/24 h) was 2.00 (95% CI, 1.34-2.98; P < .001). Microalbuminuria-related number needed to harm was 388 per year. CONCLUSION Microalbuminuria is independently associated with an increased risk for VTE.

Compliance with non-pharmacological recommendations and outcome in heart failure patients

AIMS The aim of this prospective study was to investigate the association between compliance with non-pharmacological recommendations (diet, fluid restriction, weighing, exercise) and outcome in patients with heart failure (HF). METHODS AND RESULTS In total 830 patients after an HF hospitalization participated in the study (age 70 +/- 11; left ventricular ejection fraction 34%). Compliance was measured 1 month after discharge; patients were followed for 18 months. Primary outcomes were the composite of death or HF readmission and the number of unfavourable days. Cox regression analysis was used to determine the association between primary outcome and compliance. Adjustments were made for those variables that were identified as confounders in the association between compliance and outcome. Patients who were non-compliant with at least one of the recommendations had a higher risk of mortality or HF readmission (HR 1.40; P = 0.01). Non-compliance with exercise was associated with an increased risk for mortality or HF readmission (HR 1.48; P < 0.01), while non-compliance with daily weighing was associated with an increased risk of mortality (HR 1.57; P = 0.02). Non-compliance (overall) and non-compliance with exercise were both associated with a higher risk for HF readmission [HR 1.38; P < 0.05(overall) and HR 1.55; P < 0.01(exercise)]. Patients who were overall non-compliant or with weighing and exercise had more unfavourable days than compliant patients. CONCLUSION Non-compliance with non-pharmacological recommendations in HF patients is associated with adverse outcome.

High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin

Hereditary deficiencies of protein S, protein C and antithrombin are known risk factors for first venous thromboembolism. We assessed the absolute risk of recurrence, and the contribution of concomitant thrombophilic defects in a large cohort of families with these deficiencies. Annual incidence of recurrence was estimated in 130 deficient patients, with separate estimates for those with each of protein S, protein C, and antithrombin deficiency, and in eight non-deficient patients with prior venous thromboembolism. All patients were also tested for factor V Leiden, prothrombin G20210A, high levels of factors VIII, IX and XI, and hyperhomocysteinemia. There were 81 recurrent events among 130 deficient patients. Median follow-up was 4.6 years. Annual incidences (95% confidence interval) of recurrent venous thromboembolism were 8.4% (5.8-11.7) for protein S deficiency, 6.0% (3.9-8.7) for protein C deficiency, 10.0% (6.1-15.4) for antithrombin deficiency, and overall 7.7% (6.1-9.5). Relative risk of recurrence in patients with a spontaneous versus provoked first event was 1.5 (0.95-2.3). Cumulative recurrence rates at 1, 5 and 10 years were 15%, 38% and 53%. Relative risk of recurrence with concomitant defects was 1.4 (0.7-2.6) (1 defect) and 1.4 (0.8-2.7) (> or =2 defects). Annual incidence was 1.0% (0.03-5.5) in eight non-deficient patients. Annual incidence of major bleeding in deficient patients on oral anticoagulant treatment was 0.5% (0.2-1.0). We conclude that patients with a hereditary protein S, protein C or antithrombin deficiency appear to have a high absolute risk of recurrence. This risk is increased after a first spontaneous event, and by concomitance of other thrombophilic defects.

Caregiver burden in partners of Heart Failure patients; limited influence of disease severity

In complying with required life style changes Heart Failure (HF) patients often depend on their partners. However providing care may cause burden and affect the health of these partners. The aim of this study was to investigate determinants of caregiver burden in order to identify caregivers who are at risk.

A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three-year follow-up

OBJECTIVES This study was done to identify the best treatment for an isolated high-grade stenosis of the proximal left anterior descending coronary artery (LAD). BACKGROUND Percutaneous transluminal coronary angioplasty with stenting (PCI) and off-pump coronary artery bypass grafting (surgery) are used to treat single-vessel disease of a high-grade stenosis of the proximal LAD. Midterm results of both treatments are compared in this prospective randomized study. METHODS In a single-center prospective trial, we randomly assigned 102 patients with a high-grade stenosis of the proximal LAD (American College of Cardiology/American Heart Association classification type B2 or C) to PCI (n = 51) or surgery (n = 51). Primary composite end point was freedom from Major Adverse Cardiac and Cerebrovascular Events (MACCE) at follow-up, including death, myocardial infarction, cerebrovascular accident, and repeat target vessel revascularization (TVR). Secondary end points were angina pectoris class and need for antianginal medication at follow-up. Analysis was by intention-to-treat (ITT) and received treatment (RT). RESULTS Mean follow-up time was three years (90% midrange, two to four years). Incidence of MACCE was 23.5% after PCI and 9.8% after surgery; p = 0.07 ITT (24.1% vs. 8.3%; p = 0.04 RT). After surgery a significantly lower angina pectoris class (p = 0.02) and need for antianginal medication (p = 0.01) was found compared to PCI. Target vessel revascularization was 15.7% after PCI and 4.1% after surgery (p = 0.09). CONCLUSIONS At three-year follow-up (range, two to four years), a trend in favor of surgery is observed in regard to MACCE-free survival with a significantly lower angina pectoris status and significantly lower need for antianginal medication.