Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin.

BACKGROUND: In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding. OBJECTIVE: Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA. METHODS: Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days. RESULTS: The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively). CONCLUSIONS: Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH.

Amiodarone and the development of ARDS after lung surgery.

An evaluation of amiodarone as prophylactic treatment for supraventricular tachyarrhythmias after pulmonary surgery was stopped because of a high incidence of the adult respiratory distress syndrome (ARDS) after a pneumonectomy. Retrospective analysis of all cases of resection for pulmonary neoplasm in our hospital between 1987 and 1991 indicates that amiodarone may be implicated in the development of ARDS after lung surgery.

Verapamil as prophylactic treatment for atrial fibrillation after lung operations.

BACKGROUND: Atrial fibrillation is a frequently occurring arrhythmia after thoracic operations. Preventive strategies for this complication have been extensively evaluated after cardiac operations. METHODS: We performed a prospective, open randomized study, comparing intravenous verapamil and placebo in 199 patients after pneumonectomy or lobectomy at the University Hospital of Leuven. Verapamil was administered as a bolus of 10 mg over 2 minutes followed by a 30-minute infusion of 0.375 mg/min and then 0.125 mg/min for 3 days. The patients were continuously monitored in the postoperative intensive care unit. RESULTS: Atrial fibrillation occurred in 15% of the patients receiving placebo and in 8% of the patients receiving verapamil (difference not significant). The verapamil infusion was interrupted in 9% of the patients because of bradycardia and in 14% because of hypotension. CONCLUSIONS: If tolerated, continuous intravenous verapamil infusion showed only a modest prophylactic efficacy for the occurrence of atrial fibrillation after lung operations. In the dose employed the verapamil infusion was accompanied with a high incidence of side effects necessitating interruption of the therapy.

Cardiopulmonary function after lobectomy or pneumonectomy for pulmonary neoplasm.

Resection of pulmonary tissue for bronchial carcinoma causes a decrease in vital capacity of 15% after lobectomy and 35-40% following pneumonectomy. After operation the lung becomes stiffer and elastic recoil pressure and transdiaphragmatic pressure at TLC increase. Maximum effort tolerance decreases after pneumonectomy with a normal pulmonary artery pressure at rest and an increase in pulmonary artery pressure and in pulmonary vascular resistance on effort, compared to preoperative values. Cardiac output and stroke volume during effort show a decrease after operation with an increase in peripheral arterial blood pressure and in peripheral vascular resistance. Arterial oxygen saturation on effort decreases after pneumonectomy, possibly due to the absolute decrease in diffusing capacity. When comparing resting and exercise values at identical work loads, increases in systemic arterial blood pressure, pulmonary and systemic vascular resistance and arteriovenous oxygen difference were similar although generally less pronounced after lobectomy compared to pneumonectomy; cardiac output, stroke volume and oxygen consumption showed the same tendency to decrease after lobectomy and pneumonectomy.

Acute pulmonary oedema in patients with primary pulmonary hypertension and normal pulmonary capillary wedge pressure.

Acute pulmonary oedema with normal pulmonary capillary wedge pressure, occurred in 2 patients with primary pulmonary hypertension, probably due to venoocclusive diseases. In both cases an increase in cardiac output induced by vasodilator therapy with a calcium antagonist or a viral infection with fever lead to an increase in hydrostatic pulmonary capillary pressure which was not identical to the pulmonary capillary wedge pressure.

Acute haemodynamic effects of lisinopril and captopril in patients with severe congestive heart failure.

The acute haemodynamic effects of several equivalent dosages of lisinopril and captopril were compared in patients with severe class III or IV congestive heart failure. The evaluation was started with a low dose of 2.5 mg lisinopril o.d. or 6.25 mg captopril t.i.d. and subsequent daily increases to 5 and 10 mg lisinopril o.d. or 12.5 and 25 mg captopril t.i.d. Captopril had an earlier onset of action compared to lisinopril and caused larger diurnal fluctuations of the haemodynamic parameters. Lisinopril provoked a more pronounced decrease in pulmonary capillary wedge pressure (PCWP) than captopril and only lisinopril increased the cardiac index significantly. Side-effects of hypotension or increase in serum creatinine leading to withdrawal according to protocol were noted in 3 patients on each drug. Increases in dosage caused very little increase in haemodynamic effect, suggesting that complete suppression of the angiotensin-converting enzyme may not be necessary for an optimal clinical response.

Phentolamine infusion in cor pulmonale due to chronic obstructive pulmonary disease.

Continuous phentolamine infusion, produced a marked decrease in pulmonary arterial pressure and pulmonary vascular resistance with an increase in cardiac output, in the majority of a group of 13 patients with chronic obstructive pulmonary disease and cor pulmonale. Changes in vital capacity, forced expiratory volume in one second, arterial blood gas values and peripheral blood pressure were not significant except in one patient. The changes in the pulmonary circulation are probably due to the alpha blocking effect of phentolamine, although a direct effect of the drug on vascular smooth muscle can not be excluded.

Evaluation of the safety and efficacy of amrinone in chronic obstructive lung disease with cor pulmonale.

In a pilot study the effect of a bolus dose of amrinone intravenously (IV), 0.5 or 1 mg/kg body weight, in 10 patients with chronic obstructive lung disease and cor pulmonale was evaluated. We found that the higher dose of 1.0 mg/kg IV significantly (P less than 0.05) decreased the mean pulmonary artery pressure and pulmonary wedge pressure without significant changes in cardiac output, in systemic blood pressure or in arterial blood gas values. No adverse effects were recorded in any of the patients.

Are ACE-inhibitors or ARB's still needed for cardiovascular prevention in high risk patients? Insights from profess and transcend.

The HOPE and EUROPA clinical studies have shown that treatment with the angiotensin-converting enzyme (ACE) inhibitors, ramipril and perindopril, may reduce the occurrence of major cardiovascular events in patients with proven atherosclerotic disease. The recently published results of the PRoFESS and TRANSCEND trials completed the much needed information concerning the use of an angiotensin receptor blocker for patients at high risk of cardiovascular events. PROFESS compared a therapy of telmisartan 80 mg daily with placebo in patients with a recent ischemic stroke. The difference in the primary outcome of first recurrent stroke was not statistically significant between telmisartan and placebo. The secondary outcome of major cardiovascular events showed a relative risk reduction (RRR) of 7% in favour of telmisartan. This tended to be significant (p = 0.06) despite a rather short follow-up period of only 28 months. In TRANSCEND 5926 patients at high risk for cardiovascular events were randomized to a treatment with telmisartan 80 mg daily or placebo for a mean duration of follow-up of 56 months. The primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure showed a non-significant 8% RRR in favour of the telmisartan treated patients. The main secondary outcome of cardiovascular death and myocardial infarction or stroke as used in the HOPE trial showed a non-significant RRR of 13% in favour of telmisartan treated patients (p = 0.068 adjusted for multiplicity of comparisons). In comparing the Kaplan-Meier curves for the endpoint of major cardiovascular events used in HOPE, EUROPA, TRANSCEND and PRoFESS, the trends are similar. Results of most of the recently published trials have been neutral.This could partly be explained by major improvements in the optimal background therapy of the patients included. Nevertheless, the results of PRoFESS and TRANSCEND do not contradict the results from previous studies with theACE inhibitors ramipril and perindopril and the ARB telmisartan.