Search

Acute coronary syndromes (ACS) are the leading cause of mortality in Western countries. Until a few years ago, the antiplatelet drug to be administered in association with aspirin was indisputably clopidogrel. Recent data from randomized trials conducted in ACS patients have shown that the new oral antiplatelet regimens, prasugrel and ticagrelor, are associated with a significant reduction in cardiovascular events, as compared to clopidogrel. Moreover ticagrelor reduced both all-cause and cardiovascular mortality as compared to clopidogrel in the PLATO trial. However, there are intrinsic differences between the trials design and among the enrolled ACS populations, that make complex the generalization of the mortality results in the whole spectrum of ACS patients. We aimed to provide further insights into the unresolved mortality issues raised in the PLATO and TRITON-TIMI 38 trials, by analysing the effects of ticagrelor and prasugrel in the ACS populations included in the respective trials. [ABSTRACT FROM AUTHOR]

Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting.Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those <80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125μg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg−1bolus, maximum 5000U, followed by an infusion of 7Ukg−1h−1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly.Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly. [ABSTRACT FROM PUBLISHER]

The recent evolution in therapeutic options for acute coronary syndromes (ACS) mandates early risk stratification in order to select the appropriate treatment strategy for individual patients. Simple clinical data derived from the patient's medical history and physical examination, a standard twelve-lead electrocardiogram (ECG), and determinations of biochemical markers of myocardial damage can be obtained in the emergency room and serve as a guide for deciding appropriate medical management and optimal use of available resources. Even the most important classification of the ACS is based upon a simple and dichotomous description of the ECG, where the presence of ST-segment elevation mandates an immediate attempt to restore coronary perfusion (either pharmacologically or mechanically), whereas its absence suggests pharmacological stabilization before further evaluation. Across the whole spectrum of ACS, clinical history data (such as older age, previous coronary events, and diabetes) and clinical variables (such as higher heart rate, lower blood pressure, and higher Killip class) are the most powerful prognostic determinants at multivariate analyses derived from large databases. The ECG adds significant and independent prognostic information using the analysis of qualitative (direction of ST-segment shift, associated T-wave inversion, and presence of conduction disturbances) and quantitative (number of leads involved, amount of ST- segment shifts, duration of QRS) characteristics. Biochemical markers of myocardial damage have also been identified as independent predictors of events. In addition, retrospective analyses of clinical trials have suggested that biochemical markers might serve as a guide to select pharmacological therapy. However, how to best combine electrocardiographic and biochemical data for immediate risk stratification remains to be further elucidated. [ABSTRACT FROM AUTHOR]

A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) ≥ 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds. 108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine). Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min in those on cadralazine and from 65 to 69 beats · min on prazosin. Body weight was unchanged. Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability. Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily. [ABSTRACT FROM AUTHOR]

To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2.4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P < 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P<0.01) and maximal ST change was reduced (P <0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 ± 15, felodipine 7.4 ± 2.0, placebo 6.6 ±1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P <0.01). The drug was well tolerated: however, three patients experienced ankle oedema, and one asymptomatic hypotension. These results suggest that chronic administration of felodipine, 5 mg twice daily, reduces anginal episodes and increases exercise tolerance in patients with exercise angina not controlled by beta-blocker monotherapy. [ABSTRACT FROM PUBLISHER]

The aim of this study was the electrophysiological evaluation of bisoprolol, a new highly cardioselective beta blocker, void of intrinsic sympathomimetic activity and without significant membrane stabilizing action.10 patients (4 males and 6 females, mean age 67.5 years) with cardiac arrhythmias or syncopes of undetermined origin underwent His bundle recording with incremental as well as programmed atrial and ventricular pacing in an electrophysiological study.Electrophysiological parameters were measured at basal conditions and at 15 and 30 minutes after the infusion of bisoprolol 5mg (for patient 1 to 5) and 10mg (for patient 6 to 10). All electrophysiological parameters were within normal range at basal evaluation.Bisoprolol prolongs significantly sinus cycle length, corrected sinus node recovery time, AH interval, cycle length inducing AV-node block, effective and functional refractory periods of the AV-node. All these parameters remained within normal limits and were modified to about the same extent by 5 and 10mg of the drug.No drug-related changes of QT interval were observed.Bisoprolol have been confirmed to have strictly beta-blocking properties. [ABSTRACT FROM PUBLISHER]