Pierluigi Omedè

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.

Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis

Aim Randomised trials exploring remote ischaemic preconditioning (RIPC) in patients undergoing coronary artery bypass graft (CABG) surgery have yielded conflicting data regarding potential cardiovascular and renal protection, and are individually flawed by small sample size. Methods Three investigators independently searched the MEDLINE, EMBASE and Cochrane databases to identify randomised trials testing RIPC in patients undergoing CABG. Results Nine studies with 704 patients were included. Standardised mean difference of troponin I and T release showed a significant decrease (−0.36 (95% CI −0.62 to −0.09)). This difference held true after excluding the trials with cross-clamp fibrillation, the study with off-pump CABG and studies using a flurane as anaesthetic agent (−0.41 (95% CI −0.69 to −0.12), −0.38 (95% CI −0.70 to −0.07) and −0.37 (95% CI −0.63 to −0.12), respectively). A similar trend was also obtained for patients with multivessel disease (−0.41 (95% CI −0.73 to −0.08)). The trials evaluating postoperative creatinine reported a non-significant reduction (0.02 (95% CI −0.09 to 0.13)). Moreover, the length of in-hospital stay was not influenced by the kind of treatment (weighted mean difference 0.27 (95% CI −0.24 to 0.79)). Conclusion RIPC reduced the release of troponin in patients undergoing CABG. Larger randomised trials are needed to clarify the presence of a causal relationship between RIPC-induced troponin release and clinical adverse events.

Acute coronary syndromes in human immunodeficiency virus patients: a meta-analysis investigating adverse event rates and the role of antiretroviral therapy

AIMS Highly active antiretroviral therapy (HAART) dramatically reduces human immunodeficiency virus (HIV)-associated morbidity and mortality, but adverse effects of HAART are becoming an increasing challenge, especially in the setting of acute coronary syndromes (ACS). We thus performed a comprehensive review of studies focusing on ACS in HIV patients. METHODS AND RESULTS MEDLINE/PubMed was systematically screened for studies reporting on ACS in HIV patients. Baseline, treatment, and outcome data were appraised and pooled with random-effect methods computing summary estimates [95% confidence intervals (CIs)]. A total of 11 studies including 2442 patients were identified, with a notably low prevalence of diabetes [10.86 (4.11, 17.60); 95% CI]. Rates of in-hospital death were 8.00% (2.8, 12.5; 95% CI), ascribable to cardiovascular events for 7.90% (2.43, 13.37; 95% CI), with 2.31% (0.60, 4.01; 95% CI) developing cardiogenic shock. At a median follow-up of 25.50 months (11.25, 42; 95% CI), no deaths were recorded, with an incidence of 9.42% of acute myocardial infarction (2.68, 16.17; 95% CI) and of 20.18% (9.84, 30.51; 95% CI) of percutaneous coronary revascularization. Moreover, pooled analysis of the studies reporting incidence of acute myocardial infarction in patients exposed to protease inhibitors showed an overall significant risk of 2.68 (odds ratio 1.89, 3.89; 95% CI). CONCLUSION Human immunodeficiency virus patients admitted for ACS face a substantial short-term risk of death and a significant long-term risk of coronary revascularization and myocardial infarction, especially if receiving protease inhibitors.

Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis

AIMS The prevalence of plaque rupture at the culprit lesion identified by optical coherence tomography (OCT) in different clinical subset of patients undergoing coronary angiography and its clinical predictors remain to be defined. METHODS All studies including patients with OCT evaluation of the culprit coronary plaque were included. The prevalence of culprit plaque rupture (CPR) and thin-cap fibro-atheroma (TCFA) were the primary endpoints. The factors associated with these findings were studied in a subset of patients with different clinical presentations [ST-elevation myocardial (STEMI) vs. nonST-elevation myocardial infarction (NSTEMI) vs. unstable angina (UA) vs. stable angina pectoris (SAP)]. RESULTS One hundred and fifty citations were initially appraised at the abstract level and 23 full-text studies were assessed. The mean prevalence of CPR and TCFA was 48.1% (40.5-55.8) and 48.7% (37.4-60.1), respectively. The prevalence of CPR and TCFA were higher in STEMI (70.4 and 76.6%) than in NSTEMI (55.6 and 56.3%) and UA (39.1 and 52.9%) or SAP (6.2 and 22.8%). In the overall population at meta-regression analysis, TCFA and current smoking were the only predictors of CPR (B 3.6:2.0-5.1, P < 0.001 and 0.06:0.02-0.1, P = 0.002, respectively). The factors associated with CPR were different depending on clinical presentation. Hypertension was the only clinical predictor for STEMI (B 3.3: 1.2.-5.3 P = 0.001), while advanced age (B 0.12: 0.02-0.22, P = 0.021), diabetes mellitus (B 0.04: 0.01-0.08, P = 0.012), and hyperlipidaemia (B 0.07:0.02-0.11, P = 0.005) were the predictors in NSTEMI and UA. No clinical predictor was found in SA. CONCLUSIONS Our analysis showed high rates of CPR and TCFA detected by OCT in CAD patients, especially in those with ACS, although their prevalence is not negligible in stable patients. TCFA seems to be a strong predictor of CPR in all the ACS scenarios.

Meta-Analysis of the Usefulness of Mitraclip in Patients With Functional Mitral Regurgitation

Midterm outcomes for patients presenting with heart failure and functional mitral regurgitation (MR) treated with Mitraclip remain unclear. Pubmed, Medline, and Google Scholar were systematically searched for studies enrolling patients with severe-moderate MR who underwent Mitraclip implantation. All events after at least 6 months were the primary safety end point (including death, rehospitalization for heart failure, and reinterventions), whereas change in the ejection fraction, left ventricular volumes, arterial pulmonary pressure, and left atrial diameters were considered as secondary end points. Meta-regression analysis was performed to evaluate the effect of baseline clinical and echocardiographic parameters on efficacy outcomes: 875 patients were included in 9 studies; 1.48 clips (1.3 to 1.7) for patients were implanted, and after a median follow-up of 9 months (6 to 12), 409 patients (78% [75% to 83%]) were in class New York Heart Association I/II and 57 (11% [8% to 14%]) still had moderate-to-severe MR. Overall adverse events occurred in 137 (26% [20% to 31%]) of the patients and 78 (15% [1% to 17%]) of them died; 6-minute walk test improved by 100 m (83 to 111), whereas a significant reduction in left ventricular volumes and systolic pulmonary pressure was reported. At meta-regression analysis, an increase in left ventricle systolic volumes positively affected reduction of volumes after Mitraclip, whereas atrial fibrillation reduced the positive effect of the valve implantation on ejection fraction on end-diastolic and -systolic volumes. In conclusion, Mitraclip represents an efficacious strategy for patients with heart failure and severe MR. It offers a significant improvement in functional class and in cardiac remodeling, in patients with severely dilated hearts as well, although its efficacy remains limited in the presence of atrial fibrillation.

Comparison of Mortality Rates in Women Versus Men Presenting With ST-Segment Elevation Myocardial Infarction

Women who present with coronary artery disease have different characteristics, undergo different treatment, and have a different prognosis than men. The increasing use of coronary stenting has improved the outcome of percutaneous coronary intervention (PCI). However, little is known about the outcomes for men versus women after PCI, especially for those presenting with a diagnosis of acute coronary syndrome. Thus, we compared the baseline features, management, and long-term outlook of men versus women undergoing PCI. All consecutive patients who had undergone PCI with stents at our center from July 1, 2002 to June 30, 2004 were identified retrospectively. The primary end point was the long-term rate of major adverse cardiac events (i.e., death, infarction, and repeat revascularization). The secondary end points were the individual components of the major adverse cardiac events and stent thrombosis. A total of 833 patients were included, 210 women (25.2%) and 623 men (75.8%). The women were significantly older (70.9 vs 63 years, p <0.001) and more often had diabetes mellitus (36.2% vs 21.0%, p <0.001) and hypertension (82.3% vs 73.7%, p = 0.006). The number of drug-eluting stents and the length were significantly lower in the female patients. The incidence of major adverse cardiac events after a median follow-up of 60 months was similar for both women and men (38.8% vs 46.4%, p = 0.075), with a trend toward greater mortality rate for women (21.2% vs 15.4%, p = 0.090). All other end points occurred with similar frequencies. Only in the subgroup of ST-segment elevation myocardial infarction were the rates of death significantly greater for the women than for the men (20.0% vs 8.1%; p = 0.029). In conclusion, very long-term follow-up of women undergoing PCI with coronary artery stenting resulted in similar rates of cardiac event compared to those of men, but greater care should be given to women presenting with ST-segment elevation myocardial infarction. Also, despite their greater baseline risk profile, women were significantly less likely to have received effective treatment, the use of including drug-eluting stents.

Cardiac remote ischaemic preconditioning reduces periprocedural myocardial infarction for patients undergoing percutaneous coronary interventions: a meta-analysis of randomised clinical trials

AIMS To establish the cardioprotective effect of remote ischaemic preconditioning (RIPC) in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Pubmed (MEDLINE), Cochrane and Embase were systematically searched for randomised controlled trials of RIPC in patients undergoing PCI. Periprocedural myocardial infarction (PMI) was the primary endpoint (defined as troponin elevation >3 times upper reference limit) and C-reactive protein (CRP) was a secondary endpoint. Five studies with 731 patients were included. The median age of the patients was 62 (59-68) years old, 25% were female (23-33), 29% (25-33) had diabetes mellitus, and 26.5% (19-31) presented with multivessel disease. RIPC significantly reduced the incidence of PMI (odds ratio: 0.58 [0.36, 0.93]; I2 43%), with a greater benefit when performed using the lower limb (0.21 [0.07-0.66]) compared to the upper limb (0.67 [0.46-0.99]). This reduction was enhanced for patients with multivessel disease (beta -0.05 [-0.09;-0.01], p=0.01) and with type C lesion (beta -0.014 [-0.04;-0.010], p=0.01) and did not vary according to age, female gender, diabetes mellitus, use of beta-blockers and of angiotensin converting enzyme inhibitors. Absolute risk difference was -0.10 [-0.19, -0.02], with a number needed to treat of 10 [6-50] patients to avoid one event. CRP -0.69 [-1.69, 0.31] was not significantly reduced by RIPC. CONCLUSIONS RIPC reduced the incidence of PMI following PCI, especially when performed in the lower limb and for patients with multivessel disease and complex lesions.

Prevalence and non-invasive predictors of left main or three-vessel coronary disease: evidence from a collaborative international meta-analysis including 22 740 patients

Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and meta-analysis to appraise the prevalence and predictors of LMD and 3VD. Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs). Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia. Conclusions This meta-analysis demonstrated that severe coronary disease—that is, LMD or 3VD—is more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach.

Accuracy of intravascular ultrasound and optical coherence tomography in identifying functionally significant coronary stenosis according to vessel diameter: A meta-analysis of 2,581 patients and 2,807 lesions

INTRODUCTION Accuracy of intracoronary imaging to discriminate functionally significant coronary stenosis according to vessel diameter remains to be defined. METHODS PubMed, Scopus, and Google Scholar were systematically searched for studies assessing diagnostic accuracy (area under the receiver operating characteristic curve [AUC], the primary end point) and sensitivity and specificity (the secondary end points) of minimal luminal area (MLA) or of minimal luminal diameter (MLD) derived from intravascular ultrasound (IVUS) or optical coherence tomography (OCT) to detect functionally significant stenosis as determined with fractional flow reserve (FFR). RESULTS Fifteen studies were included, 2 with 110 patients analyzing only left main (LM), 5 with 224 patients and 306 lesions using OCT, and 9 with 1532 patients and 1681 lesions with IVUS. Median MLA for the OCT studies was 1.96 mm(2) (1.85-1.98 mm(2)), 2.9 mm(2) (2.7-3.1 mm(2)) for MLA of all lesions assessed with IVUS, 2.8 mm(2) (2.7-2.9 mm(2)) for lesions with an angiographic diameter >3 mm, 2.4 mm(2) (2.4-2.5 mm(2)) for lesions <3 mm, and 5.4 mm(2) (5.1-5.6 mm(2)) for LM lesions. For OCT-MLA, AUC was 0.80 (0.74-0.86), with a sensitivity of 0.81 (0.74-0.87) and specificity of 0.77 (0.71-0.83), whereas OCT-MLD had an AUC of 0.85 (0.79-0.91), sensitivity of 0.74 (0.69-0.78), and specificity of 0.70 (0.68-0.73). For IVUS-MLA, AUC was 0.78 (0.75-0.81) for all lesions, 0.78 (0.73-0.84) for vessels with a diameter >3 mm, and 0.79 (0.70-0.89) for those with a diameter <3 mm. Left main AUC was 0.97 (0.93-1). CONCLUSION Intravascular ultrasound and OCT had modest diagnostic accuracy for identification hemodynamically significant lesions, also with specific cutoff for different diameters. Invasive imaging for assessment of LM severity demonstrated excellent correlation with FFR. What is already known about this subject? Fractional flow reserve represents the criterion standard to evaluate the prognostic value of coronary stenosis, whereas its relationship with IVUS and OCT remains to be assessed. What does this study add? Despite improvement, IVUS and OCT do not predict functional stenosis, even with dedicated cutoff, apart from LM disease. How might this impact on clinical practice? The recent guidelines of myocardial revascularization have stressed the crucial role of FFR before performing percutaneous coronary intervention on LM, whereas intravascular imaging is often exploited to drive revascularization. The present analysis stresses the point that LM percutaneous coronary intervention may be driven only by intravascular imaging, given the high accuracy for significant ischemic lesions, whereas for other vessels, these 2 techniques mirror 2 different aspects.

Meta-Analysis of Randomized Controlled Trials and Adjusted Observational Results of Use of Clopidogrel, Aspirin, and Oral Anticoagulants in Patients Undergoing Percutaneous Coronary Intervention

The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas all-cause death, myocardial infarction (MI), stent thrombosis, and stroke were secondary ones. Results were reported for all studies and separately for those deriving from randomized controlled trials or multivariate analysis. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.39 to 0.68, I2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.