Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO).

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

[ANMCO/AIGO Intersocietary consensus document: Gastroprotection in patients receiving antiplatelet and/or anticoagulant drugs]. / Documento di consenso intersocietario ANMCO/AIGO: Gastroprotezione nei pazienti in terapia antiaggregante e/o anticoagulante.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like traditional anticoagulants, novel oral anticoagulants may cause gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of gastrointestinal bleeding as compared with warfarin. However, the usefulness of PPIs in patients receiving these anticoagulants deserves to be further demonstrated. Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

ANMCO POSITION PAPER: The cardiological clinical activities in the transition phase of the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients' need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable ('not at risk') of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

Cardiac pacing in patients with neurally mediated syncope and documented asystole: effectiveness analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) Registry.

AIMS: The randomized, double-blind Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing was effective in reducing the recurrence of syncope in patients ≥ 40 years with severe asystolic, probably neurally mediated syncope (NMS), documented by implantable loop recorder (ILR). Analysis in ISSUE-3 was performed according to the intention-to-treat principle. In the present study, we performed an on-treatment analysis, which included additionally those non-randomized patients followed up in the ISSUE registry to evaluate in a better manner the effectiveness of cardiac pacing therapy. METHODS AND RESULTS: Initially, 504 patients received an ILR, 162 (32%) patients had a diagnosis consistent with NMS within a mean observation period of 15 ± 11 months: 99 (19%) patients had documentation of syncope with ≥ 3 s asystole or ≥ 6 s asystole without syncope. Sixty patients affected by asystolic NMS received cardiac pacing therapy and 86 (33 asystolic and 53 non-asystolic NMS) were untreated; 16 patients were lost to follow-up. Paced and unpaced groups had similar clinical characteristics. During subsequent follow-up, syncope recurred in 10 paced (17%) and in 40 non-paced (46%) patients. At 21 months, the estimated product-limit syncope recurrence rates were 27% [95% confidence interval (CI) 15-47] and 54% (95% CI 43-67), respectively (P = 0.01). With cardiac pacing, the risk of recurrence was reduced by 57% (hazard ratio = 0.43, 95% CI = 0.2-0.8). Complications of pacemaker therapy were haemothorax at implantation in one patient and lead dislodgement that required correction in two patients. CONCLUSION: Permanent cardiac pacing is effective in reducing recurrence of syncope in patients ≥ 40 years with severe asystolic possible NMS with a few complications. The study shows that 61% of patients with a diagnosis of NMS made by ILR received a pacemaker but 5.1 ILRs had to be implanted to find one patient who finally had a pacemaker implanted.

Is there room for containing healthcare costs? An analysis of regional spending differentials in Italy.

This work aims at identifying the determinants of health spending differentials among Italian regions and at highlighting potential margins for savings. The analysis exploits a data set for the 21 Italian regions and autonomous provinces starting in the early 1990s and ending in 2006. After controlling for standard healthcare demand indicators, remaining spending differentials are found to be significant, and they appear to be associated with differences in the degree of appropriateness of treatments, health sector supply structure and social capital indicators. In general, higher regional expenditure does not appear to be associated with better reported or perceived quality in health services. In the regions that display poorer performances, inefficiencies appear not to be uniformly distributed among expenditure items. Overall, results suggest that savings could be achieved without reducing the amount of services provided to citizens. This seems particularly important given the expected rise in spending associated with the forecasted demographic developments.

Discrepancy between clinical practice and standardized indications for an implantable loop recorder in patients with unexplained syncope.

AIM: An implantable loop recorder (ILR) is indicated in patients with unexplained syncope after complete conventional work-up. Data from the literature imply that, in clinical practice, the ILR is underused. The aim of the study was to verify if there is any discrepancy between the use of ILRs in clinical practice and the potential indications based on the most potentially appropriate guideline indications. METHOD AND RESULTS: We compared the prevalence of ILRs actually implanted in patients with unexplained syncope in the Syncope Unit Project (SUP) study and the potential one using the standard given by the guidelines. In the SUP study, 28 (18%) out of 159 patients with unexplained syncope received an ILR. Appropriate criteria for implantation of ILRs according to guidelines were present in 110 (69%) patients. Moreover, 7 (25%) of ILRs actually implanted did not satisfy the guideline standards. During the follow-up, 32% of patients who had received an ILR had a diagnosis compared with 5% of those who did not (P= 0.001). CONCLUSIONS: The estimated indications were four times higher than those observed. Moreover, in about one quarter of the cases, the use of ILRs proved to be potentially inappropriate according to guideline indications. Two-thirds of patients with unexplained syncope had indications potentially appropriate for ILRs.

Recurrent unexplained palpitations (RUP) study comparison of implantable loop recorder versus conventional diagnostic strategy.

OBJECTIVES: The aim of the study was to compare the diagnostic yield and the costs of implantable loop recorder (ILR) with those of the conventional strategy in patients with unexplained palpitations. BACKGROUND: In patients with unexplained palpitations, especially in those with infrequent symptoms, the conventional strategy, including short-term ambulatory electrocardiogram (ECG) monitoring and electrophysiological study, sometimes fails to establish a diagnosis. METHODS: We studied 50 patients with infrequent (< or =1 episode/month), sustained (>1 min) palpitations. Before enrollment, patients had a negative initial evaluation, including history, physical examination, and ECG. Patients were randomized either to conventional strategy (24-h Holter recording, a 4-week period of ambulatory ECG monitoring with an external recorder, and electrophysiological study) (n = 24) or to ILR implantation with 1-year monitoring (n = 26). Hospital costs of the 2 strategies were calculated. RESULTS: A diagnosis was obtained in 5 patients in the conventional strategy group, and in 19 subjects in the ILR group (21% vs. 73%, p < 0.001). Despite the higher initial cost, the cost per diagnosis in the ILR group was lower than in the conventional strategy group (euro 3,056 +/- euro 363 vs. euro 6,768 +/- euro 6,672, p = 0.012). CONCLUSIONS: In subjects without severe heart disease and with infrequent palpitations, ILR is a safe and more cost-effective diagnostic approach than conventional strategy.