The prognostic value of plasma fibrinogen concentrations of patients with ST-elevation myocardial infarction and treated by primary percutaneous coronary intervention: a cautionary message.

BACKGROUND: Fibrinogen elevation is associated with a worse prognosis in patients with acute coronary syndrome (ACS). The aim of the present study was to assess the prognostic value of increased fibrinogen concentrations in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: A total of 428 STEMI patients treated with primary PCI were retrospectively selected (median age: 62 years; 82.5% males) from a continuous case series of 832 ACS patients. Plasma fibrinogen concentrations were measured before PCI and after 24, 48, and 72 hours. In the 4-year follow-up, one major adverse cardiovascular event (MACE) occurred in 111 patients (40%): 17 re-STEMI (7%), 64 re-PCI (22%), 22 cardiac deaths (7%), and eight non ST-elevated acute coronary syndromes (NSTEACS, 4%). RESULTS: According to the reference change value, fibrinogen concentrations increased in 25% of patients at 24 h, 64% at 48 h and 19% at 72 h. Only fibrinogen concentrations at 48 h showed a mild association with overall MACEs (p = 0.036): the risk increased, starting from a concentration of 4 g/L. However a further multivariate model did not confirm any prognostic value. No association with specific MACEs emerged. CONCLUSIONS: In contrast to NSTEACS patients, fibrinogen concentrations increased slightly in STEMI patients after primary PCI, however, they were not as prognostic as for MACEs.

Prognostic value of cystatin C in acute coronary syndromes: enhancer of atherosclerosis and promising therapeutic target.

BACKGROUND: Cystatin C (CC) has been proposed to play a role in atherosclerosis. We aimed to review the prognostic value of CC serum/plasma levels in patients with acute coronary syndromes (ACS). METHODS: Fifteen observational longitudinal studies were selected by Medline. RESULTS: Increased CC over threshold values ranging from 0.93 to 1.3 mg/L were prognostic for death (hazard ratio; HR: 2.04-3.6) and for the occurrence of any fatal and non-fatal cardiovascular events (HR: 1.7-9.6) for patients with either ACS only or coronary heart disease and prevalent ACS. Only one study showed an increased risk for future myocardial infarction (MI) in patients with marker levels higher than 1.0 mg/L. Three studies reported the risk associated with a change of one unit of CC for long-term death (HR ranging from 1.9 to 6.3) and for the composite end point of 1 year MI and death (HR 2.15). Some studies showed the additional prognostic value contributed from CC measurements to other markers and to conventional risk scores. CONCLUSION: Despite low to moderate evidence, there is a general agreement on the significant prognostic value of CC in ACS that might encourage further research focused on risk assessment for patients with MI.

Ultra-sensitive troponin I levels to exclude acute myocardial infarction from myocardial injury.

BACKGROUND: Third generation troponin assays should aid in the rule-out of acute myocardial infarction (AMI). The study aim was to assess the capability of admission measurement of ultra-sensitive troponin I (TnI-Ultra) to exclude AMI from other myocardial injury. METHODS: The first TnI-Ultra sample from 856 patients at presentation to the Emergency Department and subsequent admission to the Cardiac Care Unit were considered in this case series. Myoglobin was simultaneously detected in 684 patients. RESULTS: The sensitivity of the first single TnI-Ultra level was 82.5% in overall AMI, and similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), admitted, respectively at 3 and 8 h from symptoms. The diagnostic capability of a first single TnI-Ultra level was poor for both STEMI and NSTEMI to discriminate and rule-out overall AMI from myocardial injury, with an area under the receiver-operating curve of 0.65 and a negative likelihood ratio of 0.55. Adopting an optimal test threshold or adding myoglobin detection did not improve TnI-Ultra performances. CONCLUSIONS: The capability of a first single TnI-Ultra level to exclude AMI from other myocardial injury in early and late presenters is poor. Addition of myoglobin assay offered no further improvement and was not considered useful.

Impact of calibration fitting models on the clinical value of chromogranin A.

BACKGROUND: The clinical relevance of chromogranin A (CgA) concentrations depends on the analytical performance of the assay. The goal of the present study was to define the clinical involvements in CgA calibration models by evaluating the confidence intervals (CIs) for values from patients who were undergoing monitoring for disease. METHODS: Thirty calibration curves for the CgA assay [immunoradiometric assay (IRMA), (CIS-BIO)] were built using linear regression (LR), and four-parameter logistic models were used to estimate CIs for patient concentrations. RESULTS: We reported the inadequacy of the LR curve estimation procedure. We showed: 1) no evidence that the straight calibration line could fit the average responses, 2) non-constant and non-uniform variance of the replicated calibration responses. All tests performed in the analysis of variance and CI calculation for the calibration curve should be invalidated. The four-parameter logistic function yielded results for 16 curves only; this result could be due to the low number and inappropriate concentration of calibrators. This suggests that some aspects of the assay design should be reviewed. However, using the variance function estimated in this model, we could assess the CI for calibration curves and patient samples. CONCLUSIONS: We showed that the four-parameter logistic calibration model with estimated variance function should better support clinical interpretation of marker concentration changes in patients serially tested.

Early P2Y12 Inhibitors Escalation in Primary PCI Patients: Insights from the RENOVAMI Registry.

BACKGROUND: Early escalation from clopidogrel to new generation P2Y12 inhibitors is common practice in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Real-world data about this strategy, however, are limited. METHODS: From 2012 to 2015, 1,057 consecutive STEMI patients treated with pPCI in an Italian hub-and-spoke network were prospectively included in an observational registry (RENOVAMI, ClinicalTrials.gov Identifier: NCT01760382). We compared the prevalence, predictive factors and in-hospital outcomes of patients escalated to a new generation P2Y12 inhibitor within the first 24 hours from pPCI with those continuing on admission antiplatelet therapy. RESULTS: In the first 24 hours after pPCI, 165 patients (15.6%) were escalated from clopidogrel to a new generation P2Y12 inhibitor, while de-escalation to clopidogrel was occasional (19 patients, 1.8%) and switch between new generation P2Y12 inhibitors was rare (8 patients, 0.8%, all from ticagrelor to prasugrel). Drug eluting stent use (adjusted odds ratio [OR], 2.19, 95% confidence interval [CI], 1.55-3.08, p = 0.0002) and impaired renal function (adjusted OR, 0.19, 95% CI, 0.05-0.77, p = 0.02) were the only independent predictive factors for the decision to escalate. After adjustment for potential confounders, escalation did not predict in-hospital outcomes, whereas the overall use of new generation P2Y12 inhibitors was correlated with a better in-hospital survival (adjusted hazard ratio, 0.47, 95% CI, 0.25-0.91, p = 0.03). Moreover, escalation did not influence bleeding rates. CONCLUSIONS: In this prospective registry of STEMI patients treated with pPCI and contemporary antiplatelet therapy, early escalation to a new generation P2Y12 inhibitor appeared safe and did not significantly affect in-hospital bleeding rates.

Intracoronary Bivalirudin Bolus in ST-Elevation Myocardial Infarction Patients Treated with Primary Angioplasty: Theoretical Bases, Clinical Experience, and Future Applications.

Intracoronary thrombus is a common finding in acute coronary syndromes and often correlates with adverse prognosis and complications during percutaneous coronary interventions (PCIs). Bivalirudin, a direct thrombin inhibitor, is one of the recommended antithrombotic treatments for PCI in ST-elevation myocardial infarction (STEMI). The intracoronary administration of a bivalirudin loading dose, even if off-label, offers theoretical advantages over the standard intravenous route, providing a very high drug concentration in the infarct-related artery without increasing the total dose of the drug administered. After the description in case reports of such an approach, a larger scale experience was recently reported in a large cohort of patients with STEMI treated during primary PCI with a bivalirudin intracoronary loading dose followed by the standard intravenous maintenance infusion. As a control group, a propensity score-matched cohort of patients undergoing primary PCI treated with intravenous bivalirudin in the same institution was selected. Compared with the intravenous bolus, the intracoronary administration of bivalirudin was associated with improved ST-segment resolution, lower post-procedural peak CK-MB levels, and better Thrombolysis in Myocardial Infarction (TIMI) frame count values, without difference in bleeding rates. Thus, this new promising antithrombotic strategy, based on the intracoronary administration of a bivalirudin loading dose during primary PCI, appeared safe, improved myocardial reperfusion, and mitigated enzymatic myocardial infarct size compared with the standard intravenous protocol. Randomized trials are warranted to confirm these results and evaluate the possible long-term clinical benefits.

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.

Intracoronary vs intravenous bivalirudin bolus in ST-elevation myocardial infarction patients treated with primary angioplasty.

BACKGROUND: Intracoronary bolus administration may provide high local bivalirudin concentration without changing the global dose, potentially offering a more favorable antithrombotic effect in the infarct related artery (IRA). OBJECTIVES: The purpose of this study was to investigate the feasibility and safety of intracoronary bolus administration of bivalirudin followed by the standard intravenous infusion in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: In 245 consecutive patients treated with primary PCI, bivalirudin bolus was given directly in the IRA, followed by a standard intravenous infusion. Clinical reperfusion markers, postprocedural coronary flow indexes, and bleeding events of the intracoronary group were compared with a propensity score-matched cohort of primary PCI patients (n=245) treated with the standard bivalirudin protocol of intravenous bolus and infusion. RESULTS: Higher rates of ⩾70% ST-segment resolution (72.7% vs 60.0%, p=0.004), lower postprocedural peak CK-MB levels (188.3±148.7 vs 242.1±208.1 IU/dl, p=0.025) and better Thrombolysis in Myocardial Infarction (TIMI) frame count values (14.7 vs 17.9, p=0.001) were observed in the IC bolus group compared with the standard intravenous bolus group. Rates of bleeding were similar between groups. Only three cases of acute stent thrombosis were observed, all in the intravenous bolus group (p=0.25). CONCLUSIONS: Intracoronary bivalirudin bolus administration during primary PCI is safe and improves ST-segment resolution, postprocedural coronary flow and enzymatic infarct size compared with the standard intravenous route.

Complex Coronary Interventions with the Novel Mozec™ CTO Balloon: The MOZART Registry.

BACKGROUND: Mozec™ CTO is a novel semicompliant rapid-exchange PTCA balloon catheter with specific features dedicated to treat complex coronary lesions like chronic total occlusions (CTOs). However, no data have been reported about the performance of this device in an all-comers population with complex coronary lesions. METHODS: We evaluated the safety and success rate of Mozec™ CTO balloon in 41 consecutive patients with chronic stable angina and complex coronary lesions (15 severe calcified coronary stenoses, 15 bifurcation lesions with planned two-stent intervention, and 11 CTOs). Safety was assessed reporting the balloon burst rate after inflation exceeding the rated burst pressure (RBP) according to the manufacturer's reference table. Success was defined as the possibility to advance the device further the target lesion. RESULTS: The Mozec™ CTO balloon showed an excellent performance with a 93.3% success in crossing tight and severely calcified lesions (14/15 pts), a 93.3% success in engaging jailed side branches after stent deployment across bifurcations (14/15 pts), and a 90.9% success in crossing CTO lesions (10/11 pts). The burst rate at RBP of the Mozec™ CTO balloon was 6.7% (1/15 balloons) in the tight and severely calcified lesions, 6.7% (1/15 balloons) when dilating jailed vessels, and 9.1% (1/11 balloons) in CTOs. CONCLUSIONS: The novel Mozec™ CTO balloon dilatation catheter showed promising results when employed to treat complex lesions in an all-comers population. Further studies should clarify if this kind of balloon might reduce the need of more costly devices like over-the-wire balloons and microcatheters for complex lesions treatment.

Beta-Blockers and Nitrates: Pharmacotherapy and Indications.

Many clinically important differences exist between beta blockers. B1-selectivity is of clinical interest because at clinically used doses, b1- selective agents block cardiac b-receptors while having minor effects on bronchial and vascular b-receptors. Beta-adrenergic blocking agents significantly decrease the frequency and duration of angina pectoris, instead the prognostic benefit of beta-blockers in stable angina has been extrapolated from studies of post myocardial infarction but has not yet been documented without left ventricular disfunction or previous myocardial infarction. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. B-blockers are the firstline anti-anginal therapy in stable stable angina patients without contraindications, while nitrates are the secondline anti-anginal therapy. Despite 150 years of clinical practice, they remain fascinating drugs, which in a chronic setting still deserve investigation. This review evaluated pharmacotherapy and indications of Beta-blockers and nitrates in stable angina.

Ivabradine for Treatment of Coronary Artery Disease: From Last Chance Resort to Mainstem of a Reasoned Therapy.

Heart rate is a fundamental determinant of cardiac oxygen consumption and plays a pivotal role in the pathophysiology of chronic stable angina (CSA). Ivabradine selectively and specifically inhibits the sino-atrial If current, slowing selectively heart rate without other significant haemodynamic effects. The consequent clinical effects are a sinus rate reduction similar to that obtained with beta-blockers, but without the related haemodynamic side effects. Ivabradine clinical benefits have been demonstrated both in patients with stable coronary artery disease (CAD) with associated systolic left ventricular dysfunction or in patients with congestive heart failure (HF). In this review we focused on the pharmacology and clinical research about ivabradine in the context of anti-ischemic therapy for CAD patients. Actually most guidelines suggest ivabradine therapy as last resort antianginal drugs in patients with uncontrolled symptoms or excessive heart rate despite maximum tolerated beta-blockade. However, the peculiar pharmacologic effects of the drug suggest that most patients with CAD might benefit from adding ivabradine to their therapeutic schemata. In fact, even if the recently released main analysis of the SIGNIFY study seems not to support an employ of ivabradine in primary prevention, it is easy to imagine a future wider use of this drug in elderly patients with incomplete myocardial revascularization and in patients with total chronic coronary occlusions and failure or unacceptable risk for percutaneous or surgical coronary revascularization.

New Anti-Anginal Drugs: Ranolazine.

Chronic angina represents a condition that impairs quality of life and is associated with decreased life expectancy in the industrialized countries. Current therapies that reduce angina frequency include old drugs such as nitrates, ß -blockers and calcium antagonists. Several new investigational drugs are being tested for the treatment of chronic angina. This review will focus on ranolazine, a drug approved by the US Food and Drug Administration (FDA) in 2006 for patients with chronic angina who continue to be symptomatic despite optimized therapies. The main molecular mechanism underlying ranolazine-mediated beneficial effects has been identified as inhibition of the late Na+ current during the action potential, which potentially improves oxygen consumption, diastolic dysfunction and coronary blood flow. The aim of this review is to update the evidence for ranolazine treatment in chronic angina and discuss its therapeutic perspectives based on the most recent clinical and experimental studies.

Pathophysiology of Atherosclerotic Plaque Development.

Cardiovascular diseases and in particular coronary atherosclerotic disease are the leading cause of mortality and morbidity in the industrialized countries. Coronary atherosclerosis has been recognized for over a century and it was the subject of various studies. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis; during the last decades the basic research has focused on the study of the instability of atherosclerotic plaque. Plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes including ST - segment elevation myocardial infarction and non ST - segment elevation myocardial infarction. This is a brief review of the pathophysiology of atherosclerotic plaque development.

Ticagrelor: a novel drug for an old problem.

Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST - segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.

New insights in the pathophysiology of acute myocardial infarction detectable by a contemporary troponin assay.

OBJECTIVES: ST-elevation and non-ST-elevation myocardial infarction (STEMI, NSTEMI) are considered two distinct pathophysiologic entities. We evaluated cardiac troponin I (cTnI) release in STEMI and NSTEMI using a "contemporary" (CV>10 to 20% at the 99th percentile concentration) cTnI assay for patients undergoing early percutaneous coronary intervention (PCI). DESIGN AND METHODS: 856 patients with suspected acute coronary syndrome consecutively admitted to the Emergency Department of the Maggiore Hospital of Novara (225 STEMI and 135 NSTEMI) were selected according to: 1) early (≤ 4 h from admission) and successful PCI; and 2) cTnI measurements at ED presentation and within 24h. The influence of the MI type on cTnI concentrations at baseline and after PCI as well as the velocity of cTnI [cTnI V=absolute increase (after log conversion of cTnI measurements)/delay between the two measurements] was studied by multiple regression analysis, adjusting for patient parameters. RESULTS: A statistically significant interaction between MI type and time from symptoms was reported on cTnI concentrations (p<0.0001): STEMI and NSTEMI differed for cTnI releases at admission and after revascularization. Higher cTnI V in STEMI was detectable in patients admitted within 6h from symptoms. Baseline cTnI concentrations were lower in patients with a history of coronary artery disease (CAD) and increased with aging (p<0.0001). In the elderly (>75 years), the cTnI V was significantly increased. CONCLUSION: STEMI and NSTEMI patients have different patterns and dynamics of cTnI release influenced by the interaction with time from symptoms, by aging and history of CAD.

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.

Multi-marker network in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: when and what to measure.

BACKGROUND: Data on the correlations between biomarkers to suggest cost-effective multi-marker (MM) panels predictive for ST-elevation myocardial infarction (STEMI) patients are lacking. We sought to explore the relationship between cardiac troponin I (cTnI), C-reactive protein (CRP), B-type natriuretic peptide (BNP), and chromogranin A (CgA) accounting for biomarkers' profiles detected within 48h from successful primary percutaneous coronary intervention (PPCI). METHODS: In 73 STEMI patients cTnI, CRP, BNP, and CgA were measured before PPCI and 6, 24, and 48h later. STATIS methods generalizing Principal Component Analysis on three-way data sets were employed to extract information about: 1) similarities between patients, 2) contribution of each time of sampling and 3) correlations between biomarkers' profiles. RESULTS: STEMI patients who underwent successful PPCI emerged to have a homogeneous profile tailored on biomarkers' evaluation within 48h. Their measurements at 24h contributed the most variability and information both to patients' and to biomarkers' profiles. BNP and cTnI were highly correlated and explained the 40.1% of the total variance, whereas CgA resulted independent and explained the 26.3% of the total variance. CONCLUSIONS: Markers' measurements at 24h after PPCI contributed most information to the definition of patients' profile. BNP and cTnI resulted interchangeable in a MM panel for reporting about the extent of necrosis.

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.

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.

[ANMCO statement on prevention of thromboembolism in atrial fibrillation and role of the new oral anticoagulants]. / Documento ANMCO su prevenzione del tromboembolismo nella fibrillazione atriale e ruolo dei nuovi anticoagulanti orali.

The introduction in the therapeutic armamentarium of three new oral anticoagulants for the prevention of thromboembolism in atrial fibrillation (AF) has stimulated the development of this position paper from the Italian Association of Hospital Cardiologists (ANMCO). First, the pathophysiology of arterial thromboembolism in AF is reviewed, describing the mechanisms of action of the new oral anticoagulants, their pharmacology and pharmacokinetics, and highlighting differences and similarities observed in preclinical studies and trials. Stratification of thromboembolic and bleeding risk is made using different risk scores; a comprehensive analysis of the various international guidelines should emphasize convergences or divergences. An in-depth examination of the limitations of current therapeutic strategies for the prevention of stroke in non-valvular AF provides insight into the difficulty in maintaining adequate adherence to therapy with warfarin and a constant and effective anticoagulation, without wide fluctuations in prothrombin time international normalized ratio (INR) values. Clinical trials of new oral anticoagulants for AF are discussed in detail in the present document, with a focus on similarities and differences, efficacy and safety data, and the net clinical benefit of each new oral anticoagulant. Results obtained in elderly patients, or in patients with renal, liver and ischemic heart disease or previous stroke are reported separately, as well as those regarding combination therapy with antiplatelet agents. Finally, this document provides indications, practical applications and cost-effectiveness analysis of each new oral anticoagulant. It is of utmost importance to know how treatment should be started, how you should switch from warfarin, which patients should be maintained on warfarin, how and when cardioversion, catheter ablation or appendage closure should be performed, what drug and food interactions may affect these medications, and how treatment adherence may be improved to avoid therapy discontinuation. An accurate examination of the risk of bleeding is also provided, with special reference to laboratory monitoring of renal and hepatic function, timing for discontinuing these medications prior to surgery, and treatment of patients with major and minor bleeding.