Francesco Colombo

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.

Discontinuation of Dual Antiplatelet Therapy Over 12 Months after Acute Coronary Syndromes Increases Risk for Adverse Events in Patients Treated with Percutaneous Coronary Intervention: Systematic Review and Meta-Analysis

INTRODUCTION Duration of dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) hospitalization remains to be defined, both for patients treated medically and for those undergoing percutaneous transluminal coronary angioplasty (PTCA). METHODS PubMed, Cochrane, and Google Scholar were systematically searched for studies including patients presenting with ACS, and treated either with DAPT longer than or shorter than 12 months. Multivariable-adjusted risk estimates for death and recurrent ACS with stopping DAPT after 12 months (odds ratios [OR] 95% confidence intervals [CI]) were pooled after logarithmic transformation according to random-effect models with inverse-variance weighting. RESULTS Five studies with 49,586 patients were included. Median age was 66 (64-67) years, with 67% (65-75) males. Myocardial infarction (MI) represented the admission diagnosis for 88% (60-100) of the patients, and 66% (50-74) were treated with stenting. After a follow-up of 2.1 years (1.5-2.7), 40% (35-46) still on DAPT after 12 months and the rates of death or recurrent ACS were 16.6 (14.5-17.0). Risk of adverse events for patients stopping DAPT after 1 year was significantly increased (OR = 1.19 [1.07-1.32]) for those receiving stents, but not for patients managed medically (OR = 1.13 [0.95-1.35]). The increased risk did not vary according to age, gender, myocardial infarction as admission diagnosis, and kind of stent. CONCLUSIONS Interruption of DAPT over 12 months after ACS increases the risk of adverse events for patients treated with PTCA, but not for those managed conservatively, independently from baseline features and admission diagnosis. This hypothesis-generating finding should be tested in randomized controlled trials.

Thirty-day readmission rates after PCI in a metropolitan center in Europe: incidence and impact on prognosis.

Introduction Thirty-day readmission rates after percutaneous coronary intervention (PCI) have been related to adverse prognosis, and represent one of the most investigated indicators of quality of care. These data, however, derive from non-European centers evaluating all-cause readmissions, without stratification for diagnosis. Methods All consecutive patients undergoing PCI at our center from January 2009 to December 2011 were enrolled. Thirty-day readmissions related to postinfarction angina, myocardial infarction, unstable angina or heart failure were defined as acute coronary syndrome (ACS) or heart failure rehospitalizations. Major cardiac adverse event (MACE) was the primary outcome, and its single components (death, myocardial infarction and repeated revascularization) the secondary ones. Results A total of 1192 patients were included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%) were classified as ACS/heart failure related. During hospitalization, patients with ACS/heart failure readmissions were more likely to suffer a periprocedural myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52 vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural myocardial infarction represented the only independent predictor of an ACS/heart failure readmission [odds ratio (OR) 4.5; 1.1–16.8; P = 0.047]. After a median follow-up of 787 days (434–1027; first and third quartiles), patients with a 30-day ACS/heart failure readmission experienced higher rates of MACE, all-cause death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and 20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that ACS/heart failure 30-day readmissions were independently related to an increased risk of all-cause death (OR 3.3; 1.1–8.8; P = 0.02), differently from 30-day non-ACS/heart failure readmissions (OR 3.1; 0.7–12.9; P = 0.12). Conclusion Thirty-day readmissions after PCI in an Italian center are infrequent, and only those patients with ACS/heart failure show a detrimental impact on prognosis who have periprocedural myocardial infarction as the only independent predictor.

Sex-related differences in patients undergoing percutaneous unprotected left main stenting.

AIMS Percutaneous coronary intervention (PCI) is increasingly being used for unprotected left main (ULM) disease. Limited data are available on sex-related differences in this setting. We investigated gender-associated differences in patients undergoing stent-based PCI for ULM. METHODS AND RESULTS We analysed baseline, procedural and long-term data of patients with ULM undergoing stent-based PCI at participating centres. The primary end-point was the long-term rate of major cardiovascular events rate (MACE, i.e., the composite of death, myocardial infarction, or target lesion revascularisation). The study population included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more frequently diabetic, hypertensive or presenting with an acute coronary syndrome, and thus with a higher EuroSCORE, but were less commonly treated with drug-eluting stents (DES), in comparison to men (all p<0.01). After a median follow-up of 18 months, women showed an unadjusted higher risk of death (p=0.040), cardiac death (p=0.033), and the death/myocardial infarction (p=0.012). However, after multivariable adjustment, gender was no longer an independent predictor of death (hazard ratio=1.119 [0.804-1.558]), cardiac death (hazard ratio=1.045 [0.697-1.567]), or death/myocardial infarction (hazard ratio=0.531 [0.192-1.465]), given the predominant role of age, diabetes and EuroSCORE as independent predictors and confounders of the gender-based comparison. CONCLUSIONS Women undergoing PCI for ULM present more often with an acute coronary syndrome, are treated less frequently with DES, and have more adverse events, but these gender biases are not confirmed after adjusting for confounders. Thus, stent-based PCI for ULM offers similarly favourable clinical results in women as well as in men.

Very long-term results comparing a simple versus a complex stenting strategy in the treatment of coronary bifurcation lesions

The optimal stenting strategy for coronary bifurcation lesions has not yet been defined, especially given the lack of very long‐term data (>24 months). We compared our long‐term results of a simple vs complex stenting strategy in patients with bifurcation lesions.

A long-term comparison of drug-eluting versus bare metal stents for the percutaneous treatment of coronary bifurcation lesions.

Background — After the first exciting results on drug-eluting stents (DES), many concerns have been raised on their potential risk for late stent thrombosis.Whereas DES appear beneficial at early and mid-term for coronary bifurcation lesions, no data are available on their long-term safety in this setting in comparison to bare metal stents (BMS).We thus aimed to appraise the long-term (>2years) outcomes of patients with bifurcation lesions treated with DES vs. BMS. Methods — We abstracted baseline, procedural and follow-up data on all patients with bifurcation coronary lesions (both branches with reference vessel diameter>2.0mm) treated with stent implantation at our centre. The primary end-point was the long-term (>2 years) rate of major adverse cardiac events (MACE, i.e. cardiac death, myocardial infarction, coronary artery bypass grafting and target vessel revascularization). Results — A total of 315patients and 334 lesions were included, 84.4% treated with DES, and 15.6% treated with BMS. The side branch was stented in 108 cases, according to a provisional T in 76 (22.7%), crushing in 15 (4.5%), V in 14 (4.2%), and culottes in 1 (0.3%). In-hospital MACE occurred in 4 (1.5%) patients of the DES group and 2 (4.1%) of the BMS group (P=0.22). After 35.8±12.9months, MACE were 72 (27.1%) vs. 24 (49%), respectively (P=0.002), with cardiac death in 7 (2.6%) patients vs. 3 (6.1%, P=0.20), myocardial infarction in 12 (4.5%) vs. 6 (12.2%, P=0.42), coronary artery bypass grafting in 5 (1.9%) vs. 1 (2%, P=0.93), target lesion revascularization in 30 (11.3%) vs. 13 (26.5%, P=0.0042), and target vessel revascularization in 48 (18%) vs. 13 (26.5%, P=0.16). Definite stent thrombosis occurred in 2 (0.75%) patients in the DES group vs. 1 (2%, P=0.93) in the BMS group, whereas probable stent thrombosis was adjudicated in 5 (1.9%) vs. 2 (4%, P=0.93). Conclusion — This cohort study, reporting for the first time on the long-term outlook of patients treated with DES vs. BMS for coronary bifurcation lesions, supports the overall safety and efficacy of DES in comparison to BMS. Specifically, even after several years of follow-up, repeat revascularizations appeared significantly lower with DES, and stent thromboses occurred with equivalent frequency in both DES and BMS groups.

Diffuse coronary disease: short- and long-term outcome after percutaneous coronary intervention

AIM The aim of this study was to evaluate short- and long-term results of PCI (percutaneous coronary intervention) in patients with small vessel coronary artery disease and the prognostic impact of the extension and the length of coronary lesions. METHODS AND RESULTS All consecutive patients treated with PCI in our centre between July 2002 and December 2004 were included and divided into two groups according to the diameter of the implanted stents: small vessel disease was defined as requiring implantation of stents < 2.75 mm in diameter. The primary end point was the long-term incidence of major adverse cardiac events (MACE), the composite of cardiac mortality, nonfatal myocardial reinfarction, and repeated percutaneous target vessel revascularization (re-PTCA TVR). 1599 patients were treated by PCI: 419 (26.2%) were implanted with 2.75 mm or smaller stents. At both 1 and 36 months as well as at 53 + 20 months of follow-up small vessel stenting was associated with a higher rate of MACE (4.2% vs 2.1%, P= 0.028; 20.3% vs 17.9%, P <0.001; 27.5% vs 22.4%, P= 0.04, respectively). Multivariate analysis showed higher rates of revascularization for patients with small vessel disease regardless of lesion length. Rates of death were higher in patients with small vessels and long lesions. CONCLUSION Atherosclerotic involvement of small vessels in patients with CAD confers a higher short- and long-term risk of adverse outcome after PCI.

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.

Impact of an optical coherence tomography guided approach in acute coronary syndromes: A propensity matched analysis from the international FORMIDABLE-CARDIOGROUP IV and USZ registry

Aim. To determine the potential clinical impact of OCT (Optical Coherence Tomography) during primary percutaneous coronary intervention in patients presenting with ACS (Acute Coronary Syndrome). Methods and Results. FORMIDABLE is a multicentre retrospective registry enrolling all patients presenting with ACS and treated with an OCT‐guided approach, while the USZ registry enrolled patients treated with a standard angiography guided approach. Multivariate adjustment was performed via a propensity score matching. The number stents useds was the primary outcome, while the incidence of MACE (a composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) was the secondary endpoint. A total of 285 patients OCT‐guided and 1,547 angiography guided patients were enrolled, resulting in 270 for each cohort after propensity score with matching. Two stents were used in 12% versus 34%; 3 stents in 8% versus 38% of the patients (P < 0.001). After a follow up of 700 days (450–890), there was no difference in myocardial infarction (6% vs. 6%, P = 0.86), while MACE (11% vs. 16%, P = 0.06), target vessel revascularization (2% vs. 4%, P = 0.15) and stent thrombosis rates (0% vs. 2.7%, P = 0.26) were numerically lower for the OCT‐guided cohort but none of these endpoints did reach statistical significance. Conclusions. An OCT‐guided approach reduced the number of stents used, number of patients treated with more than one stent, while there was no statistically significant difference in clinical endpoints while most of them were numerically lower, including stent thrombosis rates.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8–2.5, P<0.001) and bleedings (HR 1.5, 1.1–2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4–0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3–0.8, P=0.02), statins (RR 0.3, 0.2–0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3–0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6–1.5, P=0.9) were neutral. Conclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).