1Design of the Primary Prevention Parameters Evaluation (PREPARE) trial of implantablecardioverter defibrillators to reduce patient morbidity [NCT00279279]

BACKGROUND: Implantable Cardioverter Defibrillator (ICD) therapy has been proven to be beneficial and efficacious for the treatment of serious ventricular tachyarrhythmias in primary prevention patients. However, primary prevention patients appear to have a lower incidence of ventricular arrhythmias in comparison to secondary prevention patients and consequently likely experience a higher proportion of detections due to supraventricular arrhythmias. Recent trials have demonstrated that strategic and specific programming choices reduce the number of inappropriate shocks and that anti-tachycardia pacing (ATP) is an effective alternative to shock therapy for many sustained ventricular arrhythmias. METHODS: The Primary Prevention Parameters Evaluation (PREPARE) study is a multi-center cohort study, evaluating the efficacy of a pre-specified strategic profile of VT/VF detection and therapy settings in 700 primary prevention patients in an effort to safely reduce the number of shock therapies delivered. The patients, both with and without cardiac resynchronization therapy, are compared to a well-qualified set (n = 691) of historical controls derived from the MIRACLE ICD and EMPIRIC trials. This manuscript describes the design of the PREPARE study. The study results, to be presented separately, will characterize the efficacy of this programming set (PREPARE) compared with physician-tailored programming (MIRACLE ICD and EMPIRIC)

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure

Azimilide vs. placebo and sotalol for persistent atrial fibrillation : the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial

Aims: Treatment of atrial fibrillation remains a major clin. challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease. Methods and results To evaluate the efficacy of azimilide, a new class III anti-arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned elec. cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy anal. was based on event recurrence, which was defined as atrial fibrillation lasting &rt; 24 h, or requiring DC cardioversion. Median time to recurrence was 14 days for azimilide, 12 days for placebo, and 28 days for sotalol (P= 0.0320 when comparing azimilide with placebo; P= 0.0002 when comparing azimilide with sotalol). The placebo-to-azimilide hazard ratio was 1.291 (95% CI: 1.022-1.629) and the sotalol-to-azimilide hazard ratio was 0.652 (95% CI: 0.523-0.814). Adverse events causing patient withdrawal were more frequent (P<0.01) in patients on azimilide (12.3%) and on sotalol (13.9%) than on placebo (5.4%). Eight patients in the sotalol (3.5%) and 16 in the azimilide (7.6%) group interrupted the study because of QTc prolongation. Torsade de pointes was reported in five patients of the azimilide group. The percentage of patients who completed the 26 wk study period without events were 19% for azimilide, 15% for placebo, and 33% for sotalol (P<0.01). Unsuccessful day 4 cardioversion, arrhythmia recurrence, and adverse events were the main causes of withdrawal from the study. Conclusion This study demonstrates that the anti-arrhythmic efficacy of azimilide is slightly superior to placebo but significantly inferior to sotalol in patients with persistent AF. The modest anti-arrhythmic efficacy and high rate of torsade de pointes and marked QTc prolongation limit azimilide utilization for the treatment of AF

Erhohte Flecainid-Plasmakonzentrationen bei Herzinsuffizienz.

In 42 patients with heart failure who were on long-term treatment with flecainide (2 X 100 mg daily by mouth) plasma concentration of flecainide was measured before the morning dose and compared with the clinical grade of heart failure or left ventricular ejection fraction (in the levo-angiogram). Mean plasma flecainide concentration was 415 +/- 244 ng/ml (110-1035 ng/ml), mean ejection fraction 55 +/- 17.7% (24-84%) (r = -0.60). In seven patients with plasma concentrations over 700 ng/ml (870 +/- 150 ng/ml) in clinical grade III or IV, ejection fractions were 24, 25, 25, 30, 33, 37 and 44%, respectively. In two patients (ejection fraction of 24 and 25%, respectively) the morning plasma concentration was around 1000 ng/ml. The results point to possible high plasma flecainide concentrations--at times in the toxic range--in patients who are in heart failure. In patients with marked reduction in left ventricular pumping function who are on long-term flecainide treatment, a reduction in dosage or monitoring of plasma flecainide concentration is indicated