Use and misuse of multivariable approaches in interventional cardiology studies on drug-eluting stents: a systematic review.

Aims: Randomized clinical trials (RCTs) are the most reliable evidence, even if they require important resource and logistic efforts. Large, cost-free and real-world datasets may be easily accessed yielding to observational studies, but such analyses often lead to problematic results in the absence of careful methods, especially from a statistic point of view. We aimed to appraise the performance of current multivariable approaches in the estimation of causal treatment and effects in studies focusing on drug-eluting stents (DES). Methods and Results: Pertinent studies published in the literature were searched, selected, abstracted, and appraised for quality and validity features. Six studies with a logistic regression were included, all of them reporting more than 10 events for covariates and different length of follow-up, with an overall low risk of bias. Most of the 15 studies with a Cox proportional hazard analysis had a different follow-up, with less than 10 events for covariates, yielding an overall low or moderate risk of bias. Sixteen studies with propensity score were included: the most frequent method for variable selection was logistic regression, with underlying differences in follow-up and less than 10 events for covariate in most of them. Most frequently, calibration appraisal was not reported in the studies, on the contrary of discrimination appraisal, which was more frequently performed. In seventeen studies with propensity and matching, the latter was most commonly performed with a nearest neighbor-matching algorithm yet without appraisal in most of the studies of calibration or discrimination. Balance was evaluated in 46% of the studies, being obtained for all variables in 48% of them. Conclusions: Better exploitation and methodological appraisal of multivariable analysis is needed to improve the clinical and research impact and reliability of nonrandomized studies. (J Interven Cardiol 2012;**:1-1

TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients.

BACKGROUND: Acute coronary syndromes (ACS) represent a difficult challenge for physicians. Risk scores have become the cornerstone in clinical and interventional decision making. METHODS AND RESULTS: PubMed was systematically searched for ACS risk score studies. They were divided into ACS studies (evaluating Unstable Angina; UA, Non ST Segment Elevation Myocardial Infarction; NSTEMI, and ST Segment Elevation Myocardial Infarction; STEMI), UA/NSTEMI studies or STEMI studies. The c-statistics of validation studies were pooled when appropriate with random-effect methods. 7 derivation studies with 25,525 ACS patients and 15 validation studies including 257,654 people were formally appraised. Pooled analysis of GRACE scores, both at short (0.82; 0.80-0.89 I.C 95%) and long term follow up (0.84; 0.82-0.87; I.C 95%) showed the best performance, with similar results to Simple Risk Index (SRI) derivation cohorts at short term. For NSTEMI/UA, 18 derivation studies with 56,560 patients and 18 validation cohorts with 56,673 patients were included. Pooled analysis of validations studies showed c-statistics of 0.54 (95% CI = 0.52-0.57) and 0.67 (95% CI = 0.62-0.71) for short and long term TIMI validation studies, and 0.83 (95% CI = 0.79-9.87) and 0.80 (95% CI = 0.74-0.89) for short and long term GRACE studies. For STEMI, 15 studies with 134,557 patients with derivation scores, and 17 validation studies with 187,619 patients showed a pooled c-statistic of 0.77 (95% CI = 0.71-0.83) and 0.77 (95% CI = 0.72-0.85) for TIMI at short and long term, and a pooled c-statistic of 0.82 (95% CI = 0.81-0.83) and 0.81 (95% CI = 0.80-0.82) for GRACE at short and long terms respectively. CONCLUSIONS: TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched

Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry

Aims Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood. Methods and results The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI. Conclusions Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS

COMPREHENSIVE ANALYSIS OF BASELINE OUTCOME BIOPREDICTORS IN YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA: THE ANCILLARY BIOLOGICAL STUDIES OF FONDAZIONE ITALIANA LINFOMI (FIL) MCL0208 CLINICAL TRIAL

Despite the improvement in therapeutic schedules, a relevant fraction of mantle cell lymphoma (MCL) patients still experience primary treatment failure. This is due to a deep biological heterogeneity, not adequately dissected by the clinical predictors alone, as the MIPI (MCL International Prognostic Index). The Fondazione Italiana Linfomi (FIL) MCL0208 trial (NCT02354313) is a prospective, randomized phase III trial comparing lenalidomide maintenance vs observation after an intensive citarabine containing chemo-immunotherapy followed by autologous transplantation in frontline MCL patients <66 years.[Ladetto, ASH 2018] Several biological ancillary studies were planned upfront, prospectively investigating the prognostic impact of putative biomarkers. Here we present a comprehensive analysis of the clinical impact of all the identified biopredictors