Maurizio Lazzero

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).

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).

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).

Pharmacological Adjuvant Therapies in Primary Coronary Interventions: Bivalirudin

The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular medicine over the past decade because, in comparison with unfractionated heparin, it guarantees a predictable dose-related degree of anticoagulation with a low immunogenic profile and, possibly, with reduced rates of major bleeding complications. In the past bivalirudin has been frequently employed in the management of patients with heparin-induced thrombocytopenia. The REPLACE-2, ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in comparison with unfractionated heparin in terms of ischemic end-points with a reduction of the bleeding rate also in patients acute coronary syndrome without ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug as a first choice anticoagulant during percutaneous coronary interventions in patients with ST-elevation myocardial infarction. In fact the bivalirudin alone regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased in-hospital bleeding rates and short and long term mortality. Given the body of clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the leading place among the proposed anticoagulation strategies in the setting of acute coronary syndromes. The duration of the bivalirudin infusion after PCI and the optimal oral antiplatelet regimen associated to bivalirudin are important issues to be solved in future randomized controlled studies.

Intracoronary bivalirudin: a new way to appease the hostile thrombus?

Intracoronary thrombi are a common finding in the setting of acute coronary syndromes and correlate with intraprocedural complications, adverse prognosis and unpredictable response to standard pharmacological and interventional treatment. Interventional cardiologists have learned to fear the so-called hostile thrombus, with its aggressive and unstable behavior often leading to abrupt and refractory vessel closure. Here we report a case series of intracoronary bivalirudin administration to treat massive intracoronary thrombi, leading to rapid clot disappearance and coronary blood flow restoration. Interventional cardiologists might consider intracoronary bivalirudin administration as a bailout strategy during unusual critical situations.

Below normal pre-procedural cardiac troponin I levels are associated with an adverse prognosis after percutaneous coronary interventions.

AIMS To evaluate the prognostic implications of baseline cardiac troponin (cTn) values in the normal range in stable coronary artery disease (CAD) patients successfully treated with percutaneous coronary intervention (PCI). METHODS AND RESULTS We investigated the correlation between pre-procedural cTnI levels and major clinical adverse events at three years of follow-up in 1,063 consecutive stable CAD patients with normal baseline cTnI levels, successfully treated with PCI. Patients with pre-procedural cTnI levels in the upper tertile showed an increased long-term risk of overall death (HR 3.17, 95% CI: 1.62 to 6.21; p=0.0001), cardiac death (HR 5.09, 95% CI: 2.30 to 11.25; p=0.002), myocardial infarction (MI) (HR 2.34, 95% CI: 1.45 to 3.76; p=0.003) and target vessel failure (TVF) (HR 1.91, 95% CI: 1.28 to 2.84; p=0.006). Pre-procedural cTnI levels remained significantly correlated after adjustment for clinical and angiographic findings. Analysis of pre-PCI values eliminated any association of post-PCI values with prognosis. CONCLUSIONS In stable CAD patients successfully treated with PCI, pre-procedural cTnI levels, in the upper limits of the normal range, are associated with hard cardiac endpoints.

Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility

BACKGROUND Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion. METHODS We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint. RESULTS The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88±1.14 vs 0.53±0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups. CONCLUSIONS In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI.

Similar anti-inflammatory effects of intracoronary and intravenous abciximab during primary percutaneous coronary intervention: a randomized study.

Background Intracoronary Abciximab administration during primary percutaneous coronary intervention (pPCI) could offer theoretical advantages over the intravenous route. Besides antiplatelet effects, Abciximab can modulate inflammation via cross-reactivity with GPIIb/IIIa, avb3, and aMb2 receptors. The aim of our study was to assess whether the Abciximab administration route could influence its anti-inflammatory effects. Methods Eighty-nine consecutive ST elevation myocardial infarction patient candidates for pPCI were randomized to intracoronary (Group A-47 patients) or intravenous (Group B-42 patients) Abciximab bolus administration. The primary endpoint was the extent of inflammation, measured by C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1) and inter-cellular adhesion molecule 1 (ICAM-1) levels. This study is registered with ClinicalTrials.gov, NCT01757457. Results Data are expressed in medians (interquartiles). In both groups, troponin levels were similar [baseline: 0.12 (0.03–0.94) vs. 0.27 (0.07–1.24) ng/ml, P = 0.73; postprocedural: 22.00 (14.75–69.43) vs. 31.96 (8.23–7.20) ng/ml, P = 0.83]. Both groups also showed similar baseline [0.31 (0.14–0.69) vs. 0.22 (0.09–0.59) mg/ml, P = 0.80] and postprocedural CRP levels [2.28 (1.37–4.23) vs. 2.16 (1.15–3.22) mg/dl, P = 0.69], similar baseline [272.5 (224.7–340.8) vs. 262.2 (221.2–306.4) ng/ml, P = 0.33] and postprocedural soluble ICAM-1 levels [281.5 (244.6–337.4) vs. 287.2 (226.9–359.2) ng/ml P = 0.71], and similar baseline [771.6 (620.9–971.0) vs. 748.6 (592.2–838.8) ng/ml, P = 0.30] and postprocedural soluble VCAM-1 levels [785.2 (671.6–947.1) vs. 745.9 (641.1–841.9) ng/ml, P = 0.17]. In-hospital and 6-month event rates were similar in the two groups. Conclusions Our study suggests that Abciximab has similar anti-inflammatory effects irrespective of the administration route. It is unlikely that the potential clinical benefits of intracoronary Abciximab can be related to modulation of integrin receptors.

Ranolazine : Effects on Ischemic Heart

Coronary artery disease is the major cause of mortality and morbidity in the industrialized countries; in the United States of America and in Europe, it is responsible for one of every six deaths per year. In the setting of ischemic heart disease, angina pectoris and chest pain, in particular, are the major causes of emergency department accesses. Angina pectoris is a clinical syndrome characterized by discomfort typically in the chest, neck, chin and left arm induced by physical exertion, emotional stress and cold and is relieved by rest or by taking of nitrates. The main targets of treatment of angina pectoris are to improve quality of life by reducing the frequency and the severity of symptoms, to increase functional capacity and to improve prognosis. Ranolazine is a recent antianginal drug with unique methods of action. It was approved by the US Food and Drug Administration in 2006 as add-on therapy in patients symptomatic for stable angina. With the inhibition of the late sodium current, Ranolazine protects against ion deregulation, prevents cellular calcium overload and the subsequent increase in diastolic tension without impacting heart rate and blood pressure. Short term clinical trials and patent research show that add on therapy with Ranolazine in patients with chronic stable angina significantly improves exercise duration, exercise time to angina and reduces the use of nitro glycerine. Long term clinical trials showed no significant differences in the rate of cardiovascular death and myocardial infarction in patients with non-ST segment elevation acute coronary syndromes but a reduction in terms of recurrent ischemia. Ranolazine is generally well tolerated and even if it increases the duration of QTc interval it is not associated with atrial and ventricular arrhythmias. Therefore Ranolazine represents a good therapeutic approach in patients with chronic stable angina still symptomatic, while on optimal anti-ischemic therapy, or intolerant to traditional anti-ischemic drugs.