Andrea Rognoni

Biodegradable versus durable polymer drug eluting stents in coronary artery disease: Insights from a meta-analysis of 5834 patients

Background Biodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease (CAD). Methods and results Online databases including MEDLINE were searched for studies comparing BP-DES and DP-DES for obstructive CAD that reported rates for overall mortality, myocardial infarction (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late lumen loss (LLL) with a follow-up of ≥6 months. Ten studies (5834 patients) with a 1-year median follow-up were included in the meta-analysis. When comparing patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL (in-stent: weighted mean difference (WMD) −0.10 mm, 95% CI = −0.17 to −0.03 mm, p = 0.004; in-segment: WMD −0.06 mm, 95% CI = −0.10 to −0.01 mm, p = 0.01) with lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13, 95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed significant LLL reduction without differences in other clinical endpoints. Meta-regression analysis demonstrated a strong significant inverse correlation between LLL and reference coronary diameter (p < 0.001). Conclusions Our present meta-analysis showed that BP-DES when compared with DP-DES significantly reduced LLL and TVR but without clear benefits on mortality, MI and LST rates. (Clinicaltrials.gov identifier: NCT01466634).

Bioresorbable Scaffold vs. Second Generation Drug Eluting Stent in Long Coronary Lesions requiring Overlap: A Propensity-Matched Comparison (the UNDERDOGS study).

BACKGROUND Randomized clinical trials on bioresorbable scaffolds (BRS) enrolled patients with simple coronary lesions. The present study was sought to give preliminary findings about safety of BRS implantation in overlap in long coronary lesions. METHODS From June 2012 to January 2015, we prospectively collected data from 162 consecutive patients receiving overlapping BRS implantation in the 16 participating institutions. We applied a propensity-score to match BRS-treated patients with 162 patients receiving second generation drug eluting stents (DES) in overlap. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS DOCE rate did not significantly differ between the two groups (5.6% in BRS group vs. 7.4% in DES group, HR 0.79, 95%CI 0.37-3.55, p=0.6). Also stent/scaffold thrombosis did not differ between groups (1.2% in BRS group vs. 1.9% in DES group, p=0.6). Occurrence of procedural-related myocardial injury was significantly higher in the BRS group (25% vs. 12%, p=0.001), although it was not related to DOCE (HR 1.1, 95%CI 0.97-1.2, p=0.2). Imaging techniques and enhanced stent visualization systems were significantly more employed in the BRS group (p=0.0001 for both). Procedure length, fluoroscopy time and contrast dye amount were significantly higher in the BRS group (p=0.001, p=0.001 and p=0.01, respectively). CONCLUSIONS Overlapping BRS utilization in long coronary lesions showed a comparable DOCE rate at 1year if compared to second generation DES. Further and larger studies are on demand to confirm our findings.

Meta‐analysis of bioabsorbable versus durable polymer drug‐eluting stents in 20,005 patients with coronary artery disease: An update

To perform an updated meta‐analysis comparing biodegradable polymer drug eluting stents (BP‐DES) and durable polymer drug eluting stents (DP‐DES).

Long-term clinical follow-up of the multicentre, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: Cortisone plus BMS or DES veRsus BMS alone to EliminAte Restenosis (CEREA-DES)

AIMS To analyse the clinical outcome at 4 years in patients with coronary artery disease treated with bare metal stents (BMS) vs. BMS and oral prednisone, or drug-eluting stents (DES), all assuming similar adjunctive medical treatment. METHODS AND RESULTS Five Italian hospitals enrolled 375 non-diabetic, ischaemic patients without contraindications to dual anti-platelet treatment or corticosteroid therapy in a randomized controlled study. The primary endpoint was the event-free survival of cardiovascular death, myocardial infarction, and recurrence of ischaemia needing repeated target vessel revascularization at 1 year, and this was significantly lower in the BMS group (80.8%) compared with the prednisone (88.0%) and DES group (88.8%, P = 0.04 and 0.006, respectively). The long-term analysis of the primary endpoint was a pre-specified aim of the trial, and was performed at 1447 days (median, IQ range = 1210-1641). Patients receiving BMS alone had significantly lower event-free survival (75.3%) compared with 84.1% in the prednisone group (HR: 0.447; 95% CI: 0.25-0.80, P = 0.007) and 80.6% in DES patients (HR: 0.519; 95% CI: 0.29-0.93, P = 0.03). Prednisone-treated patients did not develop new treatment-related clinical problems. Drug-eluting stents patients suffered more very late stent thrombosis as a cause of spontaneous myocardial infarction. The need for target vessel revascularization remained lower in the prednisone and DES groups (13.6 and 15.2%, respectively), compared with BMS (23.2%). CONCLUSIONS The clinical benefits of prednisone compared with BMS only persisted almost unchanged at 4 years. Drug-eluting stents performed better than BMS at long-term, although the advantages observed at 1 year were in part attenuated because of the occurrence of very late stent thrombosis and late revascularizations. Clinical Trial NCT 00369356.

Drug eluting balloon versus drug eluting stent in percutaneous coronary interventions: Insights from a meta-analysis of 1462 patients

BACKGROUND Drug eluting balloons (DEB) have been developed to overcome the limitations of drug eluting stents (DES), but clinic results of various DEB studies are still not consistent. Thus, we performed a meta-analysis to compare outcomes of DEB and DES for the treatment of coronary artery disease (CAD). METHODS Medline/Web databases were searched for studies comparing DEB and DES for obstructive CAD, reporting late lumen loss (LLL) and rates for overall mortality, myocardial infarction (MI), stent thrombosis (ST) and target lesion revascularization (TLR). RESULTS 8 studies (1462 patients) were included in the meta-analysis. Compared with DES, DEB treated patients showed non-significantly higher LLL (weighted mean difference [WMD] 0.32, 95% confidence interval [CI] -0.15 to 0.78, P=0.18) and non-significantly higher rate of binary restenosis (odds ratio [OR] 1.40 [0.68-2.48], P=0.36). Mortality (OR 1.13[0.54-2.37], P=0.74), MI (OR 0.95, [0.50-1.80], P=0.87), ST (OR 1.12, [0.34-4.19], P=0.77) and TLR rates (OR 1.19[0.60-2.38], P=0.61) were similar between the 2 treatments. A pre-specified meta-regression analysis showed that LLL WMD and TLR OR were inversely correlated to the prevalence of diabetes (P<0.0001) and directly correlated to reference coronary diameters (P<0.001). CONCLUSIONS The present meta-analysis showed that compared to DES, DEB use resulted in similar clinical efficacy and safety. Thus DEB could be considered a reasonable alternative to DES for the treatment of CAD in selected clinical settings (Clinicaltrials.gov identifier: NCT01760200).

Levosimendan: From Basic Science to Clinical Trials

Levosimendan is one of the documented pharmacological agents used in the management and treatment of acute and chronic heart failure; it is a novel inodilator agent which enhanced myocardial performance without changes in oxygen consumption. The combination of positive inotropic and vasodilator effects of levosimendan relates to its Ca(2+) - sensitizing and K(+) channels opening effects. Levosimendan has been proposed, in the recent past, to be non-inferior and may have some advantages to standard inotropes; further possible indications for levosimendan have been described, in some observational studies, such as a perioperative use, cardioprotection, cardiogenic shock, sepsis and right ventricular dysfunction. The ability of levosimendan to improve myocardial function without substantially increasing oxygen consumption may appear paradoxical but is possible via improved efficacy not only with regard to the effects on the contractile apparatus of the cardiomyocytes. The aim of this review is to describe the pharmacological characteristics of levosimendan and its clinical applications. The patent review data regarding the use of levosimendan are also discussed in this review article.

Novel biomarkers in the diagnosis of acute coronary syndromes: the role of circulating miRNAs

Cardiovascular disease, in particular acute coronary syndromes (ACS), is still one of the leading causes of death in industrialized countries. ACS including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UA) are associated with lower mortality if diagnosed early. The diagnosis is based on clinical symptoms, ECG and circulating biomarker-level changes. Recent studies have shown that there are alternatives to the known biomarkers such as ultrasensitive troponin I or T and creatine kinase Mb; there are, in fact, novel biomarkers such as miRNAs. These are 22-nucleotide-long non-coding RNAs that regulate gene expression at post-transcriptional level. Several recent studies have shown that miRNAs play a physiological role in cardiovascular homeostasis and in the pathogenesis of cardiovascular disease. Expression-pattern studies of myocardial tissue reveal that several miRNAs are up- or down-regulated during myocardial infarction. The purpose of the present review is to highlight the state of the art and future views on this topic.

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.

Randomized evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: rationale and design of the REDUCE trial

BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with drug eluting stents (DES) is still under debate. Recent meta-analyses on ≤6months versus 12months DAPT suggest that bleeding rates can be reduced, without a higher rate of thrombotic complications. In particular, the COMBO dual therapy stent, being associated with early re-endothelialization, may allow for a reduction of the duration of DAPT without increasing the thrombotic risk, while reducing the risk of bleeding complications. AIM The aim of the REDUCE trial is to demonstrate the non-inferiority of a combined efficacy and safety endpoint of a short-term 3months DAPT strategy as compared to standard 12-month DAPT strategy in ACS patients treated with the COMBO stent. DESIGN A prospective, multicenter, randomized study designed to enroll 1500 patients with ACS treated with the COMBO stent. Patients will be randomized before discharge in a 1:1 fashion to either 3 or 12months of DAPT. A clinical follow-up is scheduled at 3, 6, 12, and 24months. The primary endpoint is the time to event as defined by the occurrence of one of the following: all cause mortality, myocardial infarction, stent thrombosis, stroke, target vessel revascularization or bleeding (Bleeding Academic Research Council type II, III and V) within 12months. The study has recruited patients since July 2014, and the results are expected in 2017. SUMMARY A reduction of the DAPT duration in ACS patients after PCI without affecting the thrombotic risk is an attractive option with regard to the associated bleeding risk. The REDUCE trial will be the first to investigate the efficacy and safety of a 3-month DAPT strategy compared to a 12-month DAPT strategy in an ACS only population treated with the COMBO stent.

Aortic counterpulsation in cardiogenic shock during acute myocardial infarction

Intra-aortic balloon counterpulsation is the most widely used form of mechanical hemodynamic support in the setting of cardiogenic shock due to ST-segment elevation myocardial infarction (STEMI). Intra-aortic balloon pump (IABP) is also strongly recommended (class 1b) in the current European guidelines for treatment of STEMI. The evidence of a possible benefit of IABP in this setting is based mainly on registry data and a few randomized trials. Cardiogenic shock and subsequent death due to STEMI result from three factors: hemodynamic deterioration, occurrence of multiorgan dysfunction and systemic inflammatory response. IABP does not cause an immediate improvement in blood pressure, but the recent SHOCK II trial shows positive effects on multiorgan dysfunction. Some experimental and clinical studies have indicated that IABP results in hemodynamic benefits as a result of afterload reduction and diastolic augmentation with improvement of coronary perfusion. However, the effect on cardiac output is modest and may not be sufficient to reduce mortality. Furthermore we can say that the use of IABP before coronary revascularization in the setting of STEMI complicated with cardiogenic shock may make the interventional procedure safer by improving left ventricular unloading. The purpose of the present review is to clarify the state of the art on this topic.