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Biomedical subjects

S Hohnloser

Publications and source records attributed to S Hohnloser.

At least 19 recordsLinked to original sources
PubMed2006

Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.

BACKGROUND: Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events. METHODS: Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178. RESULTS: The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively). CONCLUSION: Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.

Aged↗
PubMed2006

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Aged↗
PubMed1995

More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators.

BACKGROUND: Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models. METHODS AND RESULTS: The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg i.v. over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes later. Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge. The 10 + 10-MU r-PA group achieved better 90-minute and 5- to 14-day TIMI 3 flow (63% [CI, 55% to 71%] versus 49% [41% to 57%], P = .019, and 88% [82% to 94%] versus 71% [63% to 79%], P < .001, respectively) than the TPA group. The TIMI 3 flow in the 10 + 10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%). Global ejection fraction and regional wall motion in the 10 + 10-MU r-PA group were superior to those of the TPA group at hospital discharge (53 +/- 1.3% versus 49 +/- 1.3%, P = .034; -2.19 +/- 0.12 versus -2.61 +/- 0.13 SD per chord, P = .02, respectively). The 15-MU and 10 + 5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10 + 10-MU r-PA group. Bleeding complications were similar between the groups. CONCLUSIONS: r-PA given as a double bolus of 10 + 10 MU achieves more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. This was associated with improved global and regional left ventricular function at hospital discharge.

Coronary Angiography↗
PubMed1994

Torsade de pointes complicating drug treatment of low-malignant forms of arrhythmia: four cases reports.

In patients with malignant ventricular arrhythmias, antiarrhythmic therapy is known to carry a substantial risk of proarrhythmia. This risk is usually considered to be low when supraventricular arrhythmias or benign ventricular arrhythmias are considered. We were able to collect data on four patients without a history of life-threatening arrhythmias, in whom antiarrhythmic therapy was used and resulted in documented ventricular fibrillation or torsade de pointes. In Cases No. 1 and 2, atrial fibrillation was treated with either quinidine or quinidine and sotalol in combination. In both patients Holter monitoring, 4-12 h after conversion to sinus rhythm, documented the spontaneous occurrence of torsade de pointes degenerating into ventricular fibrillation and requiring DC shock for termination. In Case No. 3, atrial fibrillation was treated with sotalol and amiodarone for 2 months when incessant episodes of torsade de pointes were documented. In Case No. 4, frequent but unsustained ventricular arrhythmias were treated with amiodarone in a patient suffering dilative cardiomyopathy. After 6 days of treatment at a heart rate of 54 beats/min, a marked QT increase was associated with the occurrence of repetitive episodes of polymorphic ventricular tachycardia degenerating into ventricular fibrillation. None of the patients presented significant electrolyte abnormalities in the laboratory. A pathologic increase of the QTc-time was documented in Cases No. 1, 3, and 4. In all patients antiarrhythmic therapy was withdrawn after the proarrhythmic event and the patient became free of malignant tachyarrhythmias. Antiarrhythmic therapy also carries a considerable risk of proarrhythmia when "benign" cardiac arrhythmias are treated. The risk seems to be lower than in patients with malignant arrhythmias, however it includes the occurrence of lethal tachyarrhythmias. Special attention should be paid to the selection of antiarrhythmic agents when used in combination.

Aged↗
PubMed1992

Effects of amiodarone versus quinidine and verapamil in patients with chronic atrial fibrillation: results of a comparative study and a 2-year follow-up.

Rapid, reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation. The mainstay of therapy in this arrhythmia has been quinidine. More recently, amiodarone was shown in non-comparative studies to be superior to class IA agents under certain conditions. In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years, the efficacy and safety of either quinidine and verapamil (days 1 to 3, quinidine 1,500 mg/day; days 4 to 6, quinidine 1,500 mg + verapamil 240 mg/day) or amiodarone therapy (days 1 to 3, amiodarone 1,200 mg/day intravenously; days 4 to 14, amiodarone 800 mg/day orally) were randomly examined. Responders continued on their effective medication for 3 months. Thereafter, all patients were treated with a fixed regimen of quinidine (480 mg/day) plus verapamil (240 mg/day) for up to 2 years. During atrial fibrillation, quinidine reduced mean ventricular cycle length by 40 ms (-5%), quinidine and verapamil increased mean cycle length by 57 ms (8%) and amiodarone by 192 ms (28%, p less than 0.01). In addition, quinidine and verapamil had a characteristic "rate-smoothing" effect on atrioventricular conduction during atrial fibrillation. The rhythm was converted to sinus rhythm after quinidine in 5 (25%) of 20 patients and after the combination of quinidine and verapamil in 11 (55%) of 20 patients. Amiodarone restored sinus rhythm in 12 (60%) of 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1992

Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.

OBJECTIVE: To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS: Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS: One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS: Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS: Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS: A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment.

Adult↗
PubMed1992

Prevalence of circadian variations and spontaneous variability of cardiac disorders and ECG changes suggestive of myocardial ischemia in systemic arterial hypertension.

BACKGROUND: Systemic hypertension is a well-known risk factor for coronary artery disease and sudden cardiac death. Recent interest focused on the presence of malignant ventricular arrhythmias (VA) and myocardial ischemia in hypertensive patients and provided a potential link for fatal tachyarrhythmic events. METHODS AND RESULTS: We studied 150 untreated normokalemic hypertensive patients (56 +/- 9 years; 56 women and 94 men) without manifest coronary artery disease to determine prevalence, severity, and interaction of VA and significant ST segment changes induced by daily activities. One third of the patients were randomized to 4 weeks of placebo and restudied for spontaneous variability of the two parameters. All patients were included in a 3-year follow-up study. VA were observed in 129 of 150 hypertensive patients (86%) and peaked in the early morning and late afternoon. Twenty-two patients (15%) had ventricular pairs, and 20 patients (13%) had nonsustained ventricular tachycardia. Transient ST segment depression observed in 47 patients (33%; mean incidence, 2.7 +/- 0.8 episodes/24 hr) showed a characteristic circadian variation similar to VA and were asymptomatic in 93% of the episodes. At the time of transient ST segment depression, VA increased 4.6 times (p less than 0.01). After 4 weeks of placebo, marked variations in the incidence of VA (VA suppression rate -100%, or increase greater than 400%) were observed in 29% of the patients, and in 60% of all patients repetitive VA were present in only one of the two Holter recordings. Day-and-night variations of VA and transient ST segment changes were highly reproducible during the placebo period. After 3 years of follow-up, eight of 146 patients (5%) had suffered myocardial infarction, and five patients had died from cardiac events (three patients died from sudden cardiac death). Logistic regression analysis revealed left ventricular hypertrophy (relative risk, 6.1; p less than 0.01) and transient ST segment abnormalities during daily activities (relative risk, 4.4; p less than 0.05) to be of independent prognostic significance to predict cardiac events during follow-up instead of repetitive VA (relative risk, 1.3; NS). CONCLUSIONS: VA associated with a high spontaneous variability and predominantly asymptomatic transient ST segment changes are common in hypertensives; the interaction of both risk factors may provide an important link for fatal VA. Antiarrhythmic therapy is not to be recommended in the majority of patients. Presence of left ventricular hypertrophy and transient ST segment changes were the most powerful predictors of cardiac events during the follow-up.

Adult↗
PubMed1992

Differential analysis of frequency-dependent effects of antiarrhythmic drugs: importance of the saturation behavior of frequency-dependent sodium-channel blockade.

Frequency-dependent effects of class I antiarrhythmic drugs on Vmax reported in the literature are analyzed with respect to periodical drug binding to sodium channels. The analysis reveals that class I action can be differentiated according to the onset kinetics as well as to the saturation behavior of frequency-dependent sodium-channel blockade at increasing frequencies. As will be shown, class I drugs even of the same subclass (Ic) may differ markedly from each other with respect to the saturation behavior of frequency-dependent block. These findings may be of interest in view of the Cardiac Arrhythmia Suppression Trial (CAST) because the results found with flecainide and encainide in this study are usually extrapolated to other Ic drugs. Additionally, the influence of postrepolarization refractoriness caused by a class I drug on the action potential shortening during repetitive premature stimulation is compared with the effects of prolongation of absolute refractoriness induced by a class III drug.

Action Potentials↗
PubMed1992

Exercise-induced symptomatic and asymptomatic myocardial ischemia in patients with severe coronary artery disease: focus on the efficacy and safety of gallopamil.

Symptomatic and asymptomatic episodes of transient myocardial ischemia are well-known risk factors in patients with coronary artery disease. In a single-blind, randomized, and placebo-controlled study, the efficacy and safety of gallopamil was studied during a 1-week treatment period in 25 patients with high-grade coronary artery stenosis and frequent, exercise-induced episodes of myocardial ischemia. Eighteen patients were men, and seven patients were women; the mean age +/- SD was 59 +/- 7 years. After a 1-week run-in period (days 1-7), all patients were treated with gallopamil 50 mg t.i.d. (days 8-14) and placebo t.i.d. (days 15-21) or vice versa. Twenty-four-hour Holter monitoring, exercise testing, and adverse effects were controlled at days 7, 14, and 21. During the run-in period, all patients suffered a mean of 5.9 +/- 2.9 episodes of transient myocardial ischemia, mean ischemic duration was 38 +/- 29 min/day. Gallopamil increased exercise tolerance from 7.9 to 9.8 min (+24%, p < 0.05) and resulted in reduction of the weekly usage of short-acting nitrates by 45% compared to placebo. During 24-h Holter monitoring, mean heart rate at the onset of ST-segment depression increased from 106 to 118 beats/min (p < 0.05). The frequency of daily ischemic episodes was reduced after gallopamil administration from 6.1 to 3.9 episodes/day (-37%, p < 0.05), the total ischemic burden decreased for symptomatic episodes by -54% (p < 0.05) and for asymptomatic episodes by 29% (p < 0.05). Gallopamil modified the circadian distribution of ischemic episodes by modifying the morning peak of transient myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Risk stratification and long-term therapy with amiodarone in patients with idiopathic dilated cardiomyopathy].

Patients with cardiomyopathy are known to suffer from a high prevalence of tachyarrhythmic complications and sudden cardiac death. In a prospective study, 30 patients (25 men, 5 women, mean age: 52 +/- 12 years) with dilated cardiomyopathy underwent 48-h-Holter monitoring and programmed electrical stimulation and, independent from the results of the diagnostic work-up, were then randomized either to amiodarone or to a conventional or no antiarrhythmic therapy. At baseline, frequent ventricular arrhythmias (> 30 ventricular premature beats/h) were observed in 15/30 patients (50%), 13 patients (43%) had repetitive ventricular arrhythmias, additionally. Four patients suffered spontaneous sustained tachyarrhythmias. During programmed electrical stimulation, sustained monomorphic ventricular tachycardia was induced in 3/3 patients with and in 1/25 patients (4%) without a history of sustained tachycardia. Sustained monomorphic ventricular tachycardia was induced with one to two extrastimuli; three extrastimuli only increased the incidence of inducible ventricular fibrillation (8 patients, 28%). During a mean follow-up of 28 +/- 6 months 10/30 patients (33%) died for cardiac reasons (sudden cardiac death: 4/10 patients). Cardiac death was most likely in patients with a left-ventricular ejection fraction < 35% (5/18 patients, 28% versus 1/12 patients with ejection fraction > 35%, 8%) and further increased in the presence of reduced exercise tolerance and frequent and repetitive ventricular arrhythmias (4/7 patients, 57%). In the amiodarone group 4/15 patients died (27%, sudden cardiac death: one patient), while in patients not treated by amiodarone 8/15 patients died (54%; sudden cardiac death: three patients). Amiodarone therapy was well tolerated in all but one patient.

Adult↗
PubMed1991

QT-interval prolonging drugs: mechanisms and clinical relevance of their arrhythmogenic hazards.

The antiarrhythmic principle of drug-induced QT-interval prolongation is well known. However, with the widespread use of the presently known and new Class III antiarrhythmic agents under investigation, and the growing number of agents not primarily designed as antiarrhythmic drugs that potentially cause QT prolongation, we have also become aware of the proarrhythmic hazards associated with many of these agents. The proarrhythmic risk differs markedly from one agent to another and interferes with many individual clinical variables (e.g., hypokalemia, sinus bradycardia). This paper summarizes the present data on the proarrhythmic risk of drug-induced QT prolongation, including the value and problems of the rate-corrected QT interval, the mechanisms involved in the genesis of proarrhythmia, and the clinical cofactors that facilitate the occurrence of proarrhythmic events. In addition, an extensive database provides information on the known proarrhythmic risk of all currently used QT-prolonging agents.

Animals↗