A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy.

CONTEXT: A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension. OBJECTIVES: The NeuroMorfeo trial was designed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery. DESIGN: This trial is a multicentre, randomised, open-label, equivalence design. A balanced stratified randomisation scheme was maintained using a centralised randomisation service. Equivalence was tested using the two one-sided tests procedure. SETTING: Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009. PATIENTS: Adults, 18 to 75 years old, scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension. INTERVENTIONS: Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane-remifentanil or sevoflurane-fentanyl were equivalent to propofol-remifentanil. MAIN OUTCOME MEASURES: The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation. Secondary endpoints included haemodynamic parameters, quality of the surgical field, perioperative neuroendocrine stress responses and routine postoperative assessments. RESULTS: Four hundred and eleven patients [51% men, mean age 54.8 (SD 13.3) years] were enrolled. Primary outcome data were available for 380. Median (interquartiles) times to reach an Aldrete score of at least 9 were 3.48 (2.02 to 7.56), 3.25 (1.21 to 6.45) and 3.32  min (1.40 to 8.33) for sevoflurane-fentanyl, sevoflurane-remifentanil and propofol-remifentanil anaesthesia respectively, which confirmed equivalence using the two one-sided tests approach. Between-treatment differences in haemodynamic variables were small and not clinically relevant. Urinary catecholamine and cortisol responses had significantly lower activation with propofol-remifentanil. Postoperative pain and analgesic requirements were significantly higher in the remifentanil groups. CONCLUSION: Equivalence was shown for inhalational and intravenous maintenance anaesthesia in times to reach an Aldrete score of at least 9 after tracheal extubation. Haemodynamic variables, the quality of surgical field and postoperative assessments were also similar. Perioperative endocrine stress responses were significantly blunted with propofol-remifentanil and higher analgesic requirements were recorded in the remifentanil groups. TRIAL REGISTRATION: Eudract 2007-005279-32.

Effects of n-3 polyunsaturated fatty acids on malignant ventricular arrhythmias in patients with chronic heart failure and implantable cardioverter-defibrillators: A substudy of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial.

BACKGROUND: The antiarrhythmic effects of n-3 polyunsaturated fatty acids (n-3PUFA) in ischemic heart disease have been demonstrated; however, studies in patients surviving malignant ventricular arrhythmias of different etiologies treated with an implantable cardioverter-defibrillator (ICD) have given conflicting results. The purpose of this study was to assess the antiarrhythmic effect of n-3PUFA versus placebo in 566 patients with heart failure enrolled in the GISSI-HF trial who received an ICD for secondary or primary prevention of ventricular fibrillation (VF) or tachycardia (VT). METHODS: Clinical data and arrhythmic event recordings extracted from the device memory were obtained. We tested the treatment effect by a multivariate Cox model adjusting for all clinical parameters associated with the primary end point defined as time to first appropriate ICD discharge for VT/VF. RESULTS: In the 566 patients with at least one recorded follow-up visit, 1363 VT and 316 VF episodes were terminated by ICD pacing or shock over a median follow-up of 928 days. The incidence of the primary end point event was 27.3% in the n-3PUFA group and 34.0% in the placebo group (adjusted hazard rate = 0.80, 95% CI 0.59-1.09, P = .152). Patients who received 1, 2 to 3, or >3 ICD discharges were 8.9%, 7.1%, and 11.1% in the n-3PUFA group, compared with slightly higher rates of 11.1%, 10.7%, and 12.1% in the placebo group (overall P = .30). Patients with the highest 3-month increase in plasma n-3PUFA had a somewhat lower incidence of arrhythmic events. CONCLUSIONS: The results of this study, though not statistically significant, support prior evidences of an antiarrhythmic effect of n-3PUFA in patients with ICD, although they leave open the issue of whether this effect leads to a survival benefit.

Metabolic syndrome and risk of cardiovascular events after myocardial infarction.

OBJECTIVES: We aimed to assess the prevalence and prognostic role of metabolic syndrome (METS) and diabetes in post-myocardial infarction (MI) patients. BACKGROUND: Diabetes is a well known risk factor for patients with previous MI, but glycemic dysmetabolism develops over a protracted period of time. Scanty data are available on the role of METS in patients with previous MI. METHODS: Adjusted Cox's regression models, having diabetes, death, major cardiovascular events (CVE), and hospitalization for congestive heart failure (CHF) during follow-up as outcome events, were fitted on 11,323 patients with prior MI enrolled in the GISSI-Prevenzione Trial. RESULTS: At baseline, 21% and 29% of patients had diabetes mellitus and METS, respectively. The METS patients had a significant (93%) increased risk of diabetes during follow-up. As compared with control subjects, the probability of death and CVE were higher in both METS (+29%, p = 0.002; +23%, p = 0.005) and diabetic patients (+68%, p <0.0001; +47%, p <0.0001), although diabetic but not METS patients were more likely to be hospitalized for CHF (+89%, p <0.0003 and +24%, p = 0.241). Moderate (-6% to -10%) and substantial (>-10%) weight reduction were associated with a significant (18% and 41%, respectively) decreased risk of diabetes. Weight gain was significantly associated with increased risk of diabetes. The risk conferred by METS and diabetes tended to be higher among women. CONCLUSIONS: In patients with MI, METS and diabetes were highly prevalent and are associated with increased risk of death and CVE. Diabetes is also associated with increased risk of hospitalization for CHF. Weight reduction significantly decreased the risk of becoming diabetic in patients with METS.

High pulse pressure and low mean arterial pressure: two predictors of death after a myocardial infarction.

OBJECTIVES: Although the negative prognostic implication of a clinical history of arterial hypertension in myocardial infarction (MI) survivors is well known, the predictive role of the blood pressure (BP) regimen after MI is not well defined. The aim of this study was to investigate the prognostic significance of different BP indices in post-MI. METHODS AND RESULTS: We evaluated the relationship between baseline systolic, diastolic, pulse and mean arterial pressure (MAP), measured by sphygmomanometry at discharge from hospital or within 3 months of an MI, and total and cardiovascular mortality in 11 116 patients enrolled in the GISSI-Prevenzione trial. Over 3.5 years of follow-up, 999 patients died, 657 of them from cardiovascular causes. Low mean and high pulse pressure were significantly associated with total and cardiovascular mortality after controlling for potential confounders in the multivariate analysis. As compared with patients with less extreme BP values, patients with MAP of 80 mmHg or less (n = 1241; 11.2%) had a 48% higher risk of cardiovascular death [95% confidenceinterval (CI) 1.16-1.87; P = 0.001] and those with pulse pressure greater than 60 mmHg (n = 958; 8.6%) had a 35% higher risk (95% CI 1.09-1.69; P = 0.007); only four subjects (0.04%) had both a high pulse pressure and a low MAP (relative risk of cardiovascular death 3.48; 95% CI 0.48-25.88; P = 0.218). CONCLUSIONS: Our results show for the first time an additional prognostic importance of two easily measurable components of BP, definitely high pulse pressure (> 60 mmHg) and low MAP (< or = 80 mmHg), in a large sample of non-selected patients surviving MI who entered a modern programme of cardiovascular prevention.

Doppler-derived mitral deceleration time as a strong prognostic marker of left ventricular remodeling and survival after acute myocardial infarction: results of the GISSI-3 echo substudy.

OBJECTIVES: The goal of this study was to assess the impact of left ventricular (LV) diastolic filling on remodeling and survival after acute myocardial infarction (AMI). BACKGROUND: Little is known regarding the link between LV filling, its changes over time, and six-month remodeling and late survival in uncomplicated AMI. METHODS: Doppler mitral profile, end-diastolic volume index (EDVi) and end-systolic volume index (ESVi), ejection fraction (EF), and wall motion abnormalities (%WMA) were evaluated in 571 patients from the GISSI-3 Echo substudy at baseline, pre-discharge, and six months after AMI. Patients with baseline early mitral deceleration time (DT) 130 ms were assigned to the restrictive group (n = 147), and those with DT >130 ms to the nonrestrictive group (n = 424). RESULTS: Restrictive group patients had greater baseline ESVi and %WMA and lower EF than nonrestrictive group, and six-month greater LV dilation (EDVi, ESVi: p < 0.001 for EDVi and ESVi), smaller decrease in %WMA decrease (p < 0.01), and larger EF impairment (p < 0.008). Among the restrictive group, patients (n = 56) with pre-discharge persistent restrictive filling (n = 56) showed six-month greater LV enlargement (p < 0.001) and EF impairment (p < 0.009) than those (n = 91) with reversible restrictive filling. Baseline %WMA and EDVi, together with pre-discharge persistent restrictive filling, predicted severe (>20%) LV dilation. Four-year survival was 93% in nonrestrictive patients versus 88% in the restrictive group (p < 0.06), and 93% in pre-discharge reversible restrictive versus 79% in persistent restrictive (p < 0.0003). The single best predictor of mortality, by Cox analysis, was pre-discharge persistent restrictive filling (chi-square 14.88). CONCLUSIONS: Left ventricular dilation may occur even after uncomplicated AMI and may be paralleled by an improvement in LV filling. However, a baseline restrictive filling that persists at pre-discharge identifies more compromised patients at higher risk for six-month remodeling and four-year mortality.

[Determinants of late-onset heart failure in myocardial infarction survivors: GISSI Prevenzione trial results]. / Determinantes de insuficiencia cardíaca tardía postinfarto de miocardio: resultados del estudio GISSI Prevenzione.

INTRODUCTION AND OBJECTIVES: Improvement in the early phase of myocardial infarction (MI) is associated with a higher rate of late complications, including late-onset heart failure (LHF). The factors predicting LHF are not well understood. Our aims were to identify the factors predicting LHF and to determine the survival rate in these patients. PATIENTS AND METHOD: The GISSI-Prevenzione trial involved 11,323 low-risk patients (NYHA class < or = II) who had had a recent MI (< 3 months). It was a multicenter, open-label, clinical trial of the efficacy of treatment with polyunsaturated fatty acids, vitamin E, both, or neither. Patients with heart failure at baseline and those whose ejection fraction was unknown (n = 2908) were excluded from the present analysis. Late-onset heart failure was defined prospectively as hospital admission due to heart failure. A Cox regression model adjusted for major covariates was used for risk analysis. RESULTS: The study included 8415 patients. During 3.5 years of follow-up, 192 (2.3%) developed LHF. The risk of LHF could be predicted from readily available parameters: age (per year; RR=1.07; 95% CI, 1.05-1.09), ejection fraction (per 1% increment; RR=0.96; 95% CI, 0.94-0.97), heart rate (> or = 74 beats/min; RR=1.62; 95% CI, 1.21-2.16), white blood cell count (> or = 8900 per ml; RR=1.42; 95% CI, 1.05-1.94), diabetes (RR=1.62; 95% CI, 1.17-2.24), hypertension (RR=1.76; 95% CI, 1.33-2.34), peripheral artery disease (RR=2.11; 95% CI, 1.32-3.37), and reinfarction (RR=2.09; 95% CI, 1.28-3.39). LHF was associated with poor survival: (RR=2.34; 95% CI, 1.63-3.36). CONCLUSIONS: The risk of LHF in post-MI patients can be predicted from readily available parameters. LHF was associated with a poor prognosis.

Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial.

Epidemiological, experimental studies and post hoc analyses of randomized trials suggested that n-3 polyunsaturated fatty acids (PUFA) and statins could be beneficial in chronic heart failure. Two double-blind, placebo-controlled, randomized clinical trials investigated the efficacy and safety of n-3 PUFA 1 g daily (R1) and rosuvastatin 10 mg daily (R2) in patients with heart failure. In total, 6975 and 4574 patients were randomized in R1 and R2, respectively; the main reason for excluding patients from R2 being the open-label administration of statin treatment. Primary end points were death, and death or admission to hospital for cardiovascular reasons. n-3 PUFA, but not rosuvastatin, significantly decreased the two coprimary end points: 56 and 44 patients needed to be treated with n-3 PUFA for a median duration of 3.9 years to avoid one death or one cumulative event. Both drugs were safe and were tolerated. A simple and safe treatment with n-3 PUFA provides a beneficial advantage in patients with heart failure in a context of usual care.