Mario Iannaccone

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.

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis.

Background Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. Methods We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I2 statistics; p values inferior to 0.10 and I2 >25% were considered significant for heterogeneity. Results We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. Conclusions The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.

Optical coherence tomography evaluation of intermediate-term healing of different stent types: systemic review and meta-analysis

Aims The intermediate-term incidence of strut malapposition (SM) and uncovered struts (US), and the degree of neointimal thickness (NIT) according to stent type have not been characterized. Methods and results All studies of >50 patients in which optical coherence tomography was performed between 6 and 12 months after stent implantation were included. The incidences of SM and US were the co-primary end points, while NIT was the secondary end point. A total of 458 citations were initially appraised at the abstract level, and 11 full-text studies (280 652 analysed struts, 921 patients) were assessed. The 6–12 months incidences of SM and US were 5.0 and 7.8%, respectively, and the mean NIT was 206 &mgr;m. Biolimus-eluting stents (BES) and bioresorbable vascular scaffolds (BVS) had the highest SM rates (2.7 and 3.8%, respectively), while everolimus-eluting stents (EES) and fast-release zotarolimus-eluting stents (ZES) had the lowest SM rates (0.9 and 0.1%, respectively). BES and sirolimus-eluting stents (SES) had the highest US rates (7.7 and 8.8%, respectively), while bare metal stents (BMS) and ZES had the lowest US rates (0.3 and 0.3%, respectively). BMS had the greatest NIT (340 &mgr;m), while SES, EES, and BES had the least NIT. Conclusion Second-generation drug-eluting stents (DES) have better intermediate-term strut apposition and coverage than first-generation DES, BVS, and BMS. EES demonstrate the overall best combination of healing with suppression of neointimal hyperplasia at 6–12 months. Further studies with clinical correlation are warranted to determine the implications of these findings.

Provisional vs. two-stent technique for unprotected left main coronary artery disease after ten years follow up: A propensity matched analysis

AIMS There is uncertainty on which stenting approach confers the best long-term outlook for unprotected left main (ULM) bifurcation disease. METHODS AND RESULTS This is a non-randomized, retrospective study including all consecutive patients with 50% stenosis of the left main involving at least 1 of the arteries stemming from the left main treated with drug-eluting stents (DES) in 9 European centers between 2002 and 2004. Patients were divided into two groups: those treated with provisional stentings vs. those treated with two stent strategy. The outcomes of interest were 10-year rates of target lesion revascularization (TLR), major adverse cardiac events (MACE), and their components (cardiovascular death, myocardial infarction [MI], or repeat revascularization), along with stent thrombosis (ST). A total of 285 patients were included, 178 (62.5%) in the provisional stenting group and 87 (37.5%) in the two stent group. After 10 years, no differences in TLR were found at unadjusted analysis (19% vs 25%, p>0.05) nor after propensity score matching (25% vs 28%, p>0.05). Similar rates of MACE (60% vs 66%, p>0.05), death (34% vs 43%, p>0.05), MI (9% vs 14%, p>0.05) and ST were also disclosed at propensity-based analysis. CONCLUSION Even after 10 year follow-up, patients treated with provisional stenting on left main showed comparable rates of target lesion revascularization compared to two stent strategy.

Three Arterial Grafts Improve Late Survival: A Meta-Analysis of Propensity Matched Studies

Background: Little evidence shows whether a third arterial graft provides superior outcomes compared with the use of 2 arterial grafts in patients undergoing coronary artery bypass grafting. A meta-analysis of all the propensity score-matched observational studies comparing the long-term outcomes of coronary artery bypass grafting with the use of 2-arterial versus 3-arterial grafts was performed. Methods: A literature search was conducted using MEDLINE, EMBASE, and Web of Science to identify relevant articles. Long-term mortality in the propensity score-matched populations was the primary end point. Secondary end points were in-hospital/30-day mortality for the propensity score-matched populations and long-term mortality for the unmatched populations. In the matched population, time-to-event outcome for long-term mortality was extracted as hazard ratios, along with their variance. Statistical pooling of survival (time-to-event) was performed according to a random effect model, computing risk estimates with 95% confidence intervals. Results: Eight propensity score-matched studies reporting on 10 287 matched patients (2-arterial graft: 5346; 3-arterial graft: 4941) were selected for final comparison. The mean follow-up time ranged from 37.2 to 196.8 months. The use of 3 arterial grafts was not statistically associated with early mortality (hazard ratio, 0.93; 95% confidence interval, 0.71–1.22; P=0.62). The use of 3 arterial grafts was associated with statistically significantly lower hazard for late death (hazard ratio, 0.8; 95% confidence interval, 0.75–0.87; P<0.001), irrespective of sex and diabetic mellitus status. This result was qualitatively similar in the unmatched population (hazard ratio, 0.57; 95% confidence interval, 0.33–0.98; P=0.04). Conclusions: The use of a third arterial conduit in patients with coronary artery bypass grafting is not associated with higher operative risk and is associated with superior long-term survival, irrespective of sex and diabetic mellitus status.

Impact of design of coronary stents and length of dual antiplatelet therapies on ischaemic and bleeding events: a network meta-analysis of 64 randomized controlled trials and 102 735 patients

Aims The differential impact on ischaemic and bleeding events of the type of drug-eluting stent [durable polymer stents [DES] vs. biodegradable polymer stents vs. bioresorbable scaffolds (BRS)] and length of dual antiplatelet therapy (DAPT) remains to be defined. Methods and results Randomized controlled trials comparing different types of DES and/or DAPT durations were selected. The primary endpoint was Major Adverse Cardiovascular Events (MACE) [a composite of death, myocardial infarction (MI), and target vessel revascularization]. Definite stent thrombosis (ST) and single components of MACE were secondary endpoints. The arms of interest were: BRS with 12 months of DAPT (12mDAPT), biodegradable polymer stent with 12mDAPT, durable polymer stent [everolimus-eluting (EES), zotarolimus-eluting (ZES)] with 12mDAPT, EES/ZES with <12 months of DAPT, and EES/ZES with >12 months of DAPT (DAPT > 12 m). Sixty-four studies with 150 arms and 102 735 patients were included. After a median follow-up of 20 months, MACE rates were similar in the different arms of interest. EES/ZES with DAPT > 12 m reported a lower incidence of MI than the other groups, while BRS showed a higher rate of ST when compared to EES/ZES, irrespective of DAPT length. A higher risk of major bleedings was observed for DAPT > 12 m as compared to shorter DAPT. Conclusion Durable and biodegradable polymer stents along with BRS report a similar rate of MACE irrespective of DAPT length. Fewer MI are observed with EES/ZES with DAPT > 12 m, while a higher rate of ST is reported for BRS when compared to EES/ZES, independently from DAPT length. Stent type may partially affect the outcome together with DAPT length.

Rotational atherectomy in very long lesions: Results for the ROTATE registry.

Rotational atherectomy (RA) is relatively contraindicated in patients with lesions ≥25 mm of length. Aim of this study was to evaluate RA safety and efficacy in this subset of patients with new technology and devices.

Impact of postdilatation on performance of bioresorbable vascular scaffolds in patients with acute coronary syndrome compared with everolimus-eluting stents: A propensity score-matched analysis from a multicenter “real-world” registry

BACKGROUND Safety and efficacy of bioresorbable vascular scaffolds (BRS) and the role of postdilatation on outcome in acute coronary syndrome (ACS) patients compared with those of everolimus-eluting stents (EES) remain unknown. The aim of the study is to compare the safety and efficacy of BRS with EES in ACS and to investigate the role of BRS postdilatation. METHODS Consecutive ACS patients undergoing BRS implantation in 8 centers were com-pared with those with EES before and after propensity score matching. Major adverse cardiac event (MACE), myocardial infarction, and target lesion revascularization (TLR) were the primary endpoint. Sensitivity analysis was performed according to postdilatation after BRS implantation. We enrolled 303 BRS and 748 EES patients; 215 from each group were com-pared after matching, and 117 (55.2%) BRS patients were treated with postdilatation. RESULTS After a median follow-up of 24.0 months, MACE rates were higher in BRS patients than in EES patients (9.3% vs. 4.7%, p < 0.001), mainly driven by TLR (6.1% vs. 1.9%, p < 0.001). Stent thrombosis increased in the BRS group (2.8% vs. 0.9%, p = 0.01). How-ever, after sensitivity analysis, MACE rates in BRS patients with postdilatation were signifi-cantly lower than in those without, comparable to EES patients (6.0% vs. 12.6% vs. 4.7%, p < 0.001). The same trend was observed for TLR (3.4% vs. 8.4% vs. 1.9%, p < 0.001). Stent thrombosis rates were higher in both the BRS groups than in EES patients (2.6% vs. 3.2% vs. 0.9%, p = 0.045). CONCLUSIONS Postdilatation appears effective when using BRS in ACS patients. MACE rates are comparable to those of EES, although scaffold thrombosis is not negligible. Randomized prospective studies are required for further investigation.

Unmeasured Confounders in Observational Studies Comparing Bilateral Versus Single Internal Thoracic Artery for Coronary Artery Bypass Grafting: A Meta‐Analysis

Background Observational studies suggest a survival advantage with bilateral single internal thoracic artery (BITA) versus single internal thoracic artery grafting for coronary surgery, whereas this conclusion is not supported by randomized trials. We hypothesized that this inconsistency is attributed to unmeasured confounders intrinsic to observational studies. To test our hypothesis, we performed a meta‐analysis of the observational literature comparing BITA and single internal thoracic artery, deriving incident rate ratio for mortality at end of follow‐up and at 1 year. We postulated that BITA would not affect 1‐year survival based on the natural history of coronary artery bypass occlusion, so that a difference between groups at 1 year could not be attributed to the intervention. Methods and Results We searched MEDLINE and Pubmed to identify all observational studies comparing the outcome of BITA versus single internal thoracic artery. One‐year and long‐term mortality for BITA and single internal thoracic artery were compared in the propensity‐score–matched (PSM) series, that is, the form of observational evidence less prone to confounders. Thirty‐eight observational studies (174 205 total patients) were selected for final comparison. In the 12 propensity‐score–matched series (34 019 patients), the mortality reduction for BITA was similar at 1 year and at the end of follow‐up (incident rate ratio, 0.70; 95% confidence interval, 0.60–0.82 versus 0.77; 95% confidence interval, 0.70–0.85; P for subgroup difference=0.43). Conclusions Unmeasured confounders, rather than biological superiority, may explain the survival advantage of BITA in observational series.

RoTational AThErectomy in acute coronary syndrome: Early and midterm outcomes from a multicentre registry

AIMS The safety and efficacy of rotational atherectomy (RA) in patients presenting with non-ST-elevation myocardial infarction (NSTE-ACS) remain to be defined. The aim of our study was to assess the safety and efficacy of RA in NSTE-ACS patients with reference to both short- and long-term follow-up. METHODS AND RESULTS This was an observational retrospective registry which enrolled all consecutive patients undergoing RA, comparing patients with stable angina (SA) and NSTE-ACS. In addition, ACS patients were matched with those not undergoing RA. The primary endpoint was angiographic success. Procedural complications and in-hospital MACE were secondary endpoints along with MACE during follow-up. One thousand three hundred and eight patients were included: 37% (484) with an NSTE-ACS diagnosis and 63% (824) in the SA group. Angiographic success did not differ between the groups (98.8% vs. 99.2%, p=0.57). By univariate analysis procedural complications were more frequent in the NSTE-ACS group (11.3% vs. 8.0%, p=0.04). In-hospital MACE rates were comparable (5.7% vs. 5.8%, p=0.93); by multivariate analysis NSTE-ACS patients showed a non-significant trend towards a higher risk of adverse events (HR 2.39, CI: 0.96-5.96, p=0.061). MACE after a median of 27.9 months was significantly higher in the NSTE-ACS group compared with the SA group (32.4% vs. 24.2%, log-rank p<0.001), results confirmed by multivariate analysis. After propensity score matching, NSTE-ACS patients undergoing RA had similar outcomes to ACS patients who did not undergo RA (16% vs. 13%, log-rank p=0.14). CONCLUSIONS Rotational atherectomy has similar safety and angiographic outcome in patients with NSTE-ACS or SA. The higher rate of adverse cardiac events at follow-up in NSTE-ACS patients undergoing RA is comparable with a matched population of NSTE-ACS patients not undergoing RA.