Effect of metoprolol on death and cardiac events during a 2-year period after coronary artery bypass grafting

PURPOSE: To evaluate the effect of long-term treatment with metoprololafter coronary bypass grafting on death and cardiac events. METHODS: Patients in western Sweden on whom coronary artery bypass graftingwas performed between June 1988 and June 1991 were evaluatedfor inclusion during the first 3 weeks after surgery. Majorexclusion criteria were age >75 years, concomitant valvesurgery, traditional contraindications to beta-blockers andunwillingness to participate. Patients were randomized in adouble-blind fashion to 100 mg of metoprolollplacebo daily for2 weeks and thereafter 200 mg daily for 2 years. RESULTS: Of 2365 patients who were operated on, 967 were randomized toeither metoprolol (n=480) or placebo (n=487). Primary end points(death, non-fatal myocardial infarction, unstable angina pectoris,need for coronary artery bypass grafting or percutaneous transluminalangioplasty), were reached by 42 patients in the metoprololgroup (8·8%) as compared with 39 in the placebo group(8·0%) (P=0·73). Of all the patients randomizedto metoprolol, 34% withdrew from blind treatment prematurelycompared with 44% for placebo (P<0·01) CONCLUSION: Prophylactic treatment with metoprolol over a 2-year periodafter coronary artery bypass grafting did not reduce death orthe development of cardiac events. However, the 95% confidencelimits ranged from the possibility of a 30% reduction in eventsto a 68% increase in events if patients were treated with metoprololas compared with placebo.     

Safety of flecainide versus propafenone for the long-term management of symptomatic paroxysmal supraventricular tachyarrhythmias: Report from the Flecainide and Propafenone Italian Study (FAPIS) group

In order to compare the long-term safety of flecainide and propafenone,an open label, randomized, parallel group study was performedin 335 patients with paroxysmal atrial fibrillation (n=200)or paroxysmal supra ventricular tachycardia (n=135), and nohistory of heart disease. Patients were treated with an initialdaily dose of flecainide 100 mg (n=72) or propafenone 450 mg(n=63) for paroxysmal supraventricular tachycardia and flecainide200 mg (n=97) or propafenone 450 mg (n=103) for paroxysmal atrialfibrillation. Dose escalations were permitted after 2 attacks,up to a maximum of flecainide 300 mg or propafenone 900 mg.day^–1. Follow-up duration was 12 months, or when patientsstopped the treatment as a result of inadequate efficacy oradverse experiences. Twelve patients on flecainide reported 16 cardiac adverse experiences,of whom six discontinued the treatment. Seven propafenone patientshad eight cardiac adverse experiences, of whom five discontinuedthe treatment. Serious proarrhythmic events were infrequent:one case of ventricular tachycardia on propafenone; two casesof atrial fibrillation with rapid ventricular response on flecainide,associated in one patient with pulmonary oedema. An intention-to-treat analysis showed that the probability of12 months' safe and effective treatment of paroxysmal supraventriculartachycardia was 93% for flecainide and 86% for propafenone (P=0·24),whereas in paroxysmal atrial fibrillation it was 77% for flecainideand 75% for propafenone (P=0·72). In conclusion, flecainide and propafenone were safe in the long-termtreatment of patients with paroxysmal supraventricular tachyarrhythmiasand without evidence of clinically significant heart disease.     

Bleeding symptoms and laboratory correlation in patients with severe von Willebrand disease

Summary.  Type 3 von Willebrand disease (VWD) is a rare bleeding disorder with markedly decreased or absent von Willebrand factor (VWF) protein, accompanied by a parallel decrease in VWF function and factor VIII (FVIII) activity. The goal of this study was to describe the population of patients enrolled in the USA Centers for Disease Control Universal Data Collection (UDC) study with type 3 VWD, defined as a VWF:Ag of <10%, and to correlate bleeding symptoms with VWF and FVIII levels. Data on 150 patients were analysed. Almost all patients experienced bleeding episodes (98%) and required blood and/or factor product treatment (92%). While oral mucosal bleeding (the site of first bleed in 54%) was most common, subsequent muscle and joint bleeds were also seen (28%, 45%, respectively), and intracranial haemorrhage occurred in 8% of individuals. Mean age of first bleed was lower in those with either a FVIII ≤5% or a VWF:Ag <1%. Univariate marginal model analysis showed lower levels of FVIII and VWF:Ag both predicted a higher risk of joint bleeding. Longitudinal multivariate analysis found a lower FVIII level ( P  = 0.03), increasing age ( P  < 0.0001), history of joint bleeding ( P  = 0.001), higher body mass index (BMI) ( P  < 0.0001), and use of home infusion ( P  = 0.02) were all negatively associated with joint mobility. Low levels of VWF:Ag ( P  = 0.003) and male sex ( P  = 0.007) were also negatively associated with joint function. This study documents the strong bleeding phenotype in severe VWD and provides data to help target therapy, including prophylaxis, for patients most at risk of bleeding complications.     

Is on‐demand treatment effective in patients with severe haemophilia?

Summary. On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.     

Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses

Doppler echocardiographic characteristics of normally functioningAllcarbon prostheses were studied in 149 consecutive patientswith 157 valves in the mitral (n=73) and aortic (n=84) positionswhose function was considered normal by clinical and echocardiographicevaluation. In the mitral position, the mean gradient and theeffective mitral orifice area were not significantly differentin either the 25-mm or the 31-mm size valves (from 5±1to 4±1 mmHg and from 2.2±0.6 to 2.8±0.9cm², respectively; P=ns for both). Conversely, peak gradientwas significantly and inversely correlated to actual orificearea (r=–0.70; P<0.0006), decreasing from 15±3mmHg in the 25-mm size valve to 9±1 mmHg in the 31-mmsize. In the aortic position, the mean gradient was 29±8 mmHgin the 19-mm size valve; it decreased to 8±2 mmHg inthe 29-mm size. Effective prosthetic aortic valve area, calculatedusing the continuity equation, ranged between 0.9±0.1cm² for the 19-mm size valve to 4.1±0.7 cm² for the 29-mmsize. By analysis of variance, effective prosthetic aortic valvearea differentiated various valve sizes (F=25.3; P<0.0001)better than peak (F=5.34; P=0.012) or mean (F=4.34; P=0.0052)gradients alone, and it correlated better with actual orificearea (r=0.89, r=–0.70 and r=–0.65, respectively).This study provides the normal range for Doppler haemodynamiccharacteristics of the various sizes of the Allcarbon valvein the mitral and aortic positions so that prosthetic malfunctioncan be identified.     

Utilization of coronary angioplasty and cost of angioplasty disposables in 14 western European countries

An inventory has been made of the practice of angioplasty in14 European countries from 1985 onwards. The numbers of proceduresperformed varied in 1985 from 3 to 186 per million inhabitants,in 1991 from 52 to 716. All countries showed a steady increase,but the highest performer, Belgium, achieved only 55% of thenumber of angioplasties performed in 1991 in the U.S.A. No relationwas found between the number of angioplasties and death ratefor ischaemic heart disease, national income, number of cardiologistsor spending on health care. The number of catheterization laboratorieswas related to the number of procedures. Prices of angioplasty disposables varied widely between countries.In 1989 Italy and Spain had very high costs, averaging almost2500 ECU and 2000 ECU for ACS and Schneider balloon cathetersrespectively, while Switzerland and the U.K. were cheap withcosts between 700 ECU and 500 ECU for the same products. In1991 average prices for balloon catheters fell by 25% in Spain,while in Switzerland average prices increased by 10%, bringingthe almost four-fold price difference in 1989, down to a differenceof 2.5 in 1991. If the U.S.A. is taken as a standard and set against the deathrate from ischaemic heart disease in Western Europe in 1991the number of ‘missing’ angioplasties was 215 500,the U.K. accounting for 42% of this deficit.     

Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Summary. Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. Objectives: The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large‐scale, pan‐European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Results: Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty‐seven per cent of the non‐pregnancy‐related cases were male. Four hundred and seventy‐four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy‐seven patients underwent immunosuppression, and 72.6% achieved complete remission. Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.     

Prophylaxis therapy in haemophilia A: current situation in Spain

Summary. The Spanish Epidemiological Study in Haemophilia carried out in 2006 enrolled 2400 patients [2081–86.7% with haemophilia A (HA) and 319–13.3% with haemophilia B]; 465 of them (19.4%) were on prophylaxis. These rates were higher in patients with severe haemophilia (45.4%) and severe paediatric cases (72.5%). On the basis of information recorded in this study, we analysed the current situation of prophylaxis therapy administered to patients with HA in Spain, as well as their orthopaedic status. Prophylaxis was used in 399 (19.2%) patients with HA; such prophylaxis was primary (PP) in 20.3% and secondary (SP) in 75.9% of cases. Among severe HA patients, 313 (45.9%) were on prophylaxis (22.3% on PP and 74.7% on SP). Taking into account the patients’ age, 34.7% of severe HA adults were on prophylaxis (6% PP and 92.1% SP), whereas 71.5% of severe HA paediatric patients (40.5% PP and 55.4% SP) received this kind of treatment. Established haemophilic arthropathy (EHA) was detected in 142 from 313 severe HA patients (45.3%) on prophylaxis, but only in 2.9% of patients under PP vs. 59% of patients receiving SP. There was no EHA in adult severe HA patient on PP, whereas 70.4% on SP had joint damage (P < 0.00001). Among paediatric severe HA patients, EHA was detected in 3.3% under PP and 37.8% under SP (P < 0.00001). In conclusion, our data suggest that an early initiation of prophylaxis avoids EHA in the long‐term in patients with severe HA. We should emphasize the early onset of prophylaxis regimens.