Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

AimsVarious beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure.Methods and resultsWe performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20–28] of patients in the bisoprolol arm and 25% (95% CI 21–29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5–3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4–95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).ConclusionOverall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group.This study is registered with controlled-trials.com, number ISRCTN34827306.

Neurological manifestations are known to occur in patients with autoimmune diseases, often subclinically, but autonomic nervous system (ANS) involvement has rarely been studied, and studies have shown conflicting results. We performed cardiovascular ANS assessment in 125 patients with autoimmune diseases in this case-control study, including 54 patients with systemic lupus erythematosus (SLE), 39 with rheumatoid arthritis (RA), 20 with primary Sjbgren syndrome (pSS), eight patients with polymyalgia rheumatica (PR), four patients with scleroderma (Ssc) and 35 healthy control subjects. The control group was formed to approximately match the mean age of SLE, RA and pSS patients; controls did not differ significantly by gender from the autoimmune pations. All patients with were in stable condition. Autonomic nervous system dysfunction was diagnosed by applying cardiovascular reflex tests according to Ewing, and was considered to exist if at least two tests were positive. Vagal dysfunction was established by applying three tests: Valsalva manoeuvre, deep breathing test, and heart rate response to standing. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip test. In all cardiovascular reflex tests, frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05). The difference between the autoimmune patients and the controls was particularly significant in sympathetic and parasympathetic tests, with P < 0.0001. No correlation was found between disease duration, clinical manifestations, cardiovascular risk factors and diseases activity on the one hand, and ANS dysfunction on the other hand. Cardiovascular autonomic dysfunction was revealed in the majority of autoimmune patients.

No abstract

SLE and RA are associated with severe autonomic dysfunction and the presence of significant risk predictors related to the onset of sudden cardiac death.