Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5 years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.

Coronary Stents Underexpansion Successfully Treated With Shockwave Lithoplasty.

Calcified coronary plaque represents a challenging scenario for interventional cardiology. It is often associated with stent under-expansion during percutaneous coronary intervention. We report two cases of unexpected coronary stent under-expansion due to heavily calcified plaque, successfully treated with shockwave coronary lithoplasty.

Referral from vascular surgery to cardiovascular rehabilitation and related outcomes in patients with peripheral arterial disease: the THINKPAD-RELOADED survey.

The utilization of cardiovascular rehabilitation (CR) programmes in patients with Lower Extremity Peripheral Artery Disease (LEPAD) is generally poor, with limited evidence of current policies for referral. The aim of the study was to evaluate, within a cohesive network of CR and vascular surgery facilities with facilitated referral process, the clinical characteristic of LEPAD patients referred to CR and related outcomes, as compared to patients not referred. The present is an observational prospective study of consecutive patients recruited at vascular surgery facilities. Out of 329 patients observed, the average referral rate to CR was 34% (28% and 39% in patients with and without recent peripheral revascularization, p<0.05). LEPAD patients entering the CR programme were similar to those who did not according to sex, age, the vascular surgery setting of evaluation, and localization of arterial lesions. Patients with moderate intermittent claudication and patients with acute limb ischemia as index event were more represented among those who attended CR (41% vs 21% and 9% vs 2% respectively, p<0.05). Patients referred to CR had five times more episodes of acute coronary syndrome and heart failure as complication of the index event. The cardiovascular risk profile (obesity 29.5% vs 11%, p<0.05; hypercholesterolemia 80% vs 61%, p<0.05) was much worse in LEPAD patients referred to CR, but conversely, they better achieved secondary prevention targets, particularly for blood pressure control (97% vs 57%, p<0.05). All-cause 2-year mortality in the whole patients' population was 6%. Patients entering the CR programme displayed less events (13.5% vs 37.7%, p<0.05), mainly death (3.1% vs 11.3%, p<0.05) and limb-related events (4.2% vs 15.2%, p<0.05). The results of our study suggest that when a cohesive network of vascular surgery and CR facilities becomes available, the referral rate to rehabilitation may increase up to one third of eligible patients. Patients with higher comorbidity and cardiovascular risk seem to have priority in the referral process, nevertheless those with peripheral revascularization are still underestimated. Entering CR may ensure better cardiovascular risk profile and cardiovascular prognosis in LEPAD patients, and consequently the systematic adoption of this care model needs to be strongly recommended and facilitated.

High thrombotic risk increases adverse clinical events up to 5 years after acute myocardial infarction. A nationwide retrospective cohort study.

The risk of recurrent events among survivors of acute myocardial infarction (AMI) is understudied. The aim of this analysis was to investigate the role of residual high thrombotic risk (HTR) as a predictor of recurrent in-hospital events after AMI. This retrospective cohort study included 186,646 patients admitted with AMI from 2009 to 2010 in all Italian hospitals who were alive 30 days after the index event. HTR was defined as at least one of the following in the 5 years preceding AMI: previous myocardial infarction, ischemic stroke/other vascular disease, type 2 diabetes mellitus, renal failure. Risk adjustment was performed in all multivariate survival analyses. Rates of major cardiac and cerebrovascular events (MACCE) within the following 5 years were calculated in both patients without fatal readmissions at 30 days and in those free from in-hospital MACCE at 1 year from the index hospitalization. The overall 5-year risk of MACCE was higher in patients with HTR than in those without HTR, in both survivors at 30 days [hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.45-1.52; p<0.0001] and in those free from MACCE at 1 year (HR, 1.46; 95% CI, 1.41-1.51; p<0.0001). The risk of recurrent MACCE increased in the first 18 months after AMI (HR, 1.49) and then remained stable over 5 years. The risk of MACCE after an AMI endures over 5 years in patients with HTR. This is also true for patients who did not have any new cardiovascular event in the first year after an AMI. All patients with HTR should be identified and addressed to intensive preventive care strategies.

[Cardiac rehabilitation "3.0": from the acute to the chronic stage. A position paper from the Italian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR)]. / La Cardiologia Preventiva e Riabilitativa "3.0": dalle acuzie alla cronicità. Position paper del Gruppo Italiano di Cardiologia Riabilitativa e Preventiva (GICR-IACPR).

Cardiac rehabilitation (CR) represents a cardiology subspecialty that is devoted to the care of cardiac patients, early and long term after an acute event. CR aims at improving both quality of life and prognosis through risk and prognostic stratification, clinical stabilization and optimization of therapy, management of comorbidities, treatment of disability, and the provision of sustained long-term preventive and rehabilitative services.The mission of CR has changed over time. From being centred on the acute phase, health care of cardiac patients is increasingly involving the long-term chronic phase. The aim of the present position paper is to provide the state of the art of CR in Italy, discussing strengths and weaknesses as well as future perspectives.

[Treatment adherence in cardiovascular prevention]. / L'aderenza globale al trattamento nel continuum della prevenzione cardiovascolare.

Treatment adherence is a key element for (i) improving prognosis in cardiovascular and/or high-risk patients, (ii) reducing the burden of morbidity and mortality associated with cardiovascular disease at a population level, and (iii) decreasing costs due to rehospitalizations.Promotion of adherence should embrace all pharmacological and non-pharmacological interventions in cardiovascular prevention, including lifestyle and behavioral changes. In this perspective, cardiac prevention and rehabilitation programs are the most appropriate and cost-effective setting for delivering structured and multi-component interventions on patient's adherence. In this expert opinion document authored by the Italian Association for Cardiovascular Prevention and Rehabilitation, a modern reappraisal of the adherence issue is provided, together with simple, practical, and feasible suggestions to achieve this goal in the real life as well.

Cardiac Prevention and Rehabilitation "3.0": From acute to chronic phase. Position Paper of the ltalian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR).

Cardiac rehabilitation (CR) is the subspecialty of clinical cardiology dedicated to the treatment of cardiac patients, early and in the long term after an acute event. The aim of CR is to improve both quality of life and prognosis through prognostic stratification, clinical stabilization and optimization of therapy (pharmacological and non), management of comorbidities, treatment of disability, as well as through the provision and reinforcement of secondary prevention interventions and maintenaince of adherence to treatment. The mission of CR has changed over time. Once centered on the acute phase, aimed primarily at short-term survival, the healthcare of cardiac patients now increasingly involves the chronic phase where the challenge is to guarantee continuity and quality of care in the medium and long-term. The aim of the present position paper is to provide the state-of-the-art of CR in Italy, discussing its trengths and weaknesses as well as future perspectives.

[Heart rate as a therapeutic target after acute coronary syndrome and in chronic coronary heart disease]. / La frequenza cardiaca come target terapeutico dopo sindrome coronarica acuta e nella cardiopatia ischemica cronica.

For patients with stable coronary artery disease (SCAD), either after hospitalization for acute cardiac events or in the chronic phase, comprehensive treatment programs should be devoted to: (i) reducing mortality and major adverse cardiovascular events, (ii) reducing the ischemic burden and related symptoms, and (iii) increasing exercise capacity and quality of life.Heart rate (HR) has demonstrated to have prognostic value and patients beyond the limit of 70 bpm display increased risk of all the above adverse outcomes, even after adjustment for parameters such as the extension of myocardial infarction and the presence of heart failure. It is well known that a sustained HR elevation may contribute to the pathogenesis of SCAD, being the likelihood of developing ischemia, plaque instability, trigger for arrhythmias, increased vascular oxidative stress, and endothelial dysfunction the mechanisms resulting in this effect. Moreover, high HR could promote chronotropic incompetence, leading to functional disability and reduced quality of life.Despite the strong relationship between HR and prognosis, there is heterogeneity among current guidelines in considering HR as a formal therapeutic target for secondary prevention in SCAD, as far as the cut-off limit. This expert opinion document considered major trials and observational registries in the modern treatment era with beta-blockers and ivabradine, suggesting that an adequate HR control could represent a target for (i), (ii), and (iii) therapeutic goals in SCAD patients with systolic dysfunction (with major evidence for reduced left ventricular ejection fraction <40%), and a target for (ii) and (iii) goals in SCAD patients with preserved left ventricular ejection fraction. The defined cut-off limit is 70 bpm. To date, there is room for improvement of HR control, since in contemporary SCAD patients HR values <70 bpm are present in less than half of cases, even in the vulnerable phase after an acute coronary syndrome.

Early invasive versus early conservative strategy in non-ST-elevation acute coronary syndrome: An outcome research study.

BACKGROUND: An early invasive strategy (EIS) has been shown to yield a better clinical outcome than an early conservative strategy (ECS) in patients with non-ST-elevation acute coronary syndromes (NSTEACSs), particularly in those at higher risk according to the GRACE risk score. However, findings of the clinical trials have not been confirmed in registries. OBJECTIVE: To investigate the outcome of patients with NSTEACS treated according to an EIS or a ECS in a real-world all-comers outcome research study. METHODS: The primary hypothesis of the study was the non-inferiority of an ECS in comparison with an EIS as to a combined primary end-point of death, non-fatal myocardial infarction and hospital readmission for acute coronary syndromes at one year. Participating centres were divided into two groups: those with a pre-specified routine EIS and those with a pre-specified routine ECS. Two statistical analyses were performed: a) an 'intention to treat' analysis: all patients were considered to be treated according to the pre-specified routine strategy of that centre; b) a 'per protocol' analysis: patients were analysed according to the actual treatment applied. Cox model including propensity score correction was applied for all analyses. RESULTS: The intention to treat analysis showed an equivalence between EIS and ECS (11.4% vs. 11.1%) with regard to the primary end-point incidence at one year. In the three subgroups of patients according to the GRACE risk score (⩽ 108, 109-140, > 140), EIS and ECS confirmed their equivalence (5.3% vs. 3.9%, 8.4% vs. 7.6%, and 20.3% vs. 20.9%, respectively). When the per protocol analysis was applied, a reduction of the primary end-point at one year with EIS vs. ECS was demonstrated (6.2% vs. 15.3%, p=0.021); analysis of the subgroups according to the GRACE risk score numerically confirmed these data (3.1% vs. 6.5%, 5.1% vs. 10.0%, and 10.8% vs. 24.5%, respectively). CONCLUSIONS: In a real-life registry of all-comers NSTEACS patients, ECS was non-inferior to EIS; however, when EIS was applied according to clinical judgement, a reduction of clinical events at one year was demonstrated.

New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.

The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.

Efficacy and safety of novel anticoagulants versus vitamin K antagonists in patients with mild and moderate to severe renal insufficiency: Focus on apixaban.

The high risk of both stroke and major bleeding in atrial fibrillation (AF) patients with chronic kidney disease (CKD) defines an important population for whom the assessment of the balance between the risk of ischemic stroke and of bleeding is essential. The use of novel oral anticoagulants (NOACs) may be a viable option in this population due to their greater net clinical benefit than warfarin, as demonstrated by the results of the clinical phase III trials. NOACs have been found to have a greater net clinical benefit than warfarin in patients at high risk of either stroke (CHADS2≥1 or CHA2DS2-VASc score≥2) or bleeding (HAS-BLED≥3). Noteworthy, it has been found also a positive net clinical benefit with apixaban and dabigatran 110mg BID in patients with CHADS2 score=0 and HAS-BLED score≥3. At CHA2DS2-VASc score=1, apixaban and both doses of dabigatran were superior to warfarin in terms of the net clinical benefit. Available scientific evidence might help in clinical decision-making regarding the use of NOACs in patients with CKD who are at high risk for both stroke and bleeding. Overall, current findings provide a rationale for the choice of apixaban or rivaroxaban over dabigatran in patients with AF and stage III CKD. Out of the NOACs, only apixaban has been recently approved for the use in patients with end-stage renal dysfunction on hemodialysis (the recommended dose of 5mg twice daily should be halved in patients with body weight of ≤60kg and or age≥80years).

[The Italian Survey on Cardiac Rehabilitation - 2013 (ISYDE.13-Directory): national availability and organization of cardiac rehabilitation facilities]. / Italian Survey on Cardiac Rehabilitation (ISYDE.13-Directory): report su strutture, organizzazione e programmi di cardiologia riabilitativa in Italia.

BACKGROUND: The Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) and the Italian Society of Cardiologists of Accredited Hospitals (SICOA) developed the ISYDE.13 survey with the purpose to take a detailed snapshot of number, distribution, facilities, staffing levels, organization, and program details of cardiac rehabilitation (CR) units in Italy. METHODS: The study was carried out using a web-based questionnaire running on the GICR-IACPR website for 4 weeks from September 2 to 29, 2013. RESULTS: Out of 221 CR centers existing in Italy (+14% vs 2008), 191 (86%) participated in the survey. On a national basis, there is a CR unit every 268 852 inhabitants. The majority of CR units are located in public hospitals (57.1%), the remaining 42.9% in private hospitals; 130 CR centers (68%) provide inpatients care and account for 3527 beds (5.9 per 100 000 inhabitants): of these 374 are day-hospital beds and 408 are sub-intensive beds. Forty-one of the Italian in-hospital CR centers offer also outpatient programs and 61 centers (32%) offer only outpatient CR programs; 131 of the CR units (68.6%) are linked to dedicated cardiology divisions and in 77% of cases the head is a cardiologist. Home-based programs are offered by 9 centers (4.7%) and CR programs with telecare supervision by 16 (8.4%). Long-term secondary prevention follow-up programs are provided by 94 of CR services (49.2%). During one week of activity, the 191 centers completed 1335 inpatient CR programs and 971 outpatient CR programs. According to these data, it may be assumed that in Italy approximately 100 000 patients are referred annually to CR programs. CONCLUSIONS: ISYDE.13 showed an incremental trend of CR provision in Italy, particularly in outpatient programs. However, at present, the national network of CR units covers only one third of the potential requirements defined by current secondary prevention recommendations.

Effects of cigarette smoking on platelet reactivity during P2Y12 inhibition in patients with myocardial infarction undergoing drug-eluting stent implantation: results from the prospective cigarette smoking on platelet reactivity (COPTER) study.

Interaction between cigarette smoking and efficacy of oral antiplatelet drugs is not definitely elucidated. We evaluated the effects of cigarette smoking on platelet reactivity in patients receiving different oral P2Y12 antagonists after myocardial infarction (MI) and drug-eluting stent (DES) implantation. Two-hundred-five consecutive current smokers receiving DES implantation after ST-segment elevation MI were enrolled. All patients were aspirin-treated and were on chronic therapy with clopidogrel (N = 59), prasugrel (N = 71) or ticagrelor (N = 75); by protocol, all patients at baseline had no high on-treatment platelet reactivity by the VerifyNow P2Y12 assay. Platelet reactivity, expressed by P2Y12 reaction units (PRU), was measured in all patients at baseline (T0), after a 15-day period of smoking cessation (T1) and after further 15 days of smoking resumption (T2). In the overall population there was a modest, albeit significant, reduction of PRU values from T0 to T1 (from 173 ± 14 to 165 ± 17, P < 0.0001); resumption of cigarette smoking was associated with re-increase of platelet reactivity (from 165 ± 17 at T1 to 170 ± 17 at T2, P = 0.0002). These variations were consistent in the subgroups receiving clopidogrel, prasugrel or ticagrelor and were irrespective of the number of cigarettes smoked. In conclusion, cigarette smoking weakly influences antiplatelet effects of oral P2Y12 inhibition and this was irrespective of the type of antiplatelet agent; thus, interaction between cigarette smoking and efficacy of oral antiplatelet drugs is modest and unlikely translates into clinical effects (ClinicalTrials.gov Identifier: NCT02026713).

[Real-world data on novel oral anticoagulants: the added value of registries and observational studies. Focus on apixaban]. / I nuovi anticoagulanti orali nel mondo reale: il valore aggiunto dei dati dei registri e degli studi osservazionali. Focus su apixaban.

Anticoagulant therapy has been used with great effect for decades for the prevention of stroke among patients with atrial fibrillation. In recent years, the therapeutic armamentarium has been strengthened considerably, with the addition of anticoagulants acting through novel pathways. The currently available novel agents are apixaban, rivaroxaban and dabigatran. These novel oral anticoagulants (NOACs) were approved for use on the basis of major clinical trials clearly demonstrating improved risk reductions compared to warfarin for stroke and/or major bleeding events. In these studies, apixaban and dabigatran 150 mg each significantly reduced the risk of stroke, while apixaban and dabigatran 110 mg reduced the risk of major bleeding compared to warfarin. Extrapolating the results of the randomized clinical trials on NOACs to all patients is not possible, as the strict design of clinical trials yields information that is directly applicable to a relatively narrow spectrum of patients. To control for confounding variables, randomized studies restrict enrolment to a prespecified set of criteria that do not necessarily reflect the profiles of all those who could potentially benefit from these agents. Research continues using the trial databases, in an attempt to better identify patient subgroups who do or do not benefit from each of the agents. At the European Society of Cardiology (ESC) annual meetings in London in 2015 and in Rome in 2016, there were several presentations and posters providing this type of evidence. Perhaps more important, as real-world experience with these agents grows, we are beginning to obtain meaningful new information about the NOACs in everyday use. This has involved the study of large databases including patients receiving these medications in clinical situations less stringently defined than in the randomized clinical trials. These include purpose-built registries, observational studies, and analyses of healthcare administrative databases. At both ESC meetings in 2015 and 2016, a wealth of information was presented using these types of sources. In many cases, these new data reinforce the key learnings from the randomized clinical trials. The following report provides highlights of registry and other post-marketing data presented at both ESC meetings in 2015 and 2016.

Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine.

Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone.

Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more mineralocorticoid receptor-specific. From a marginal role as a potassium-sparing diuretic, spironolactone has been shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure. Also, spironolactone is safe and protective in arterial hypertension, particularly in patients with so-called resistant hypertension. Eplerenone is the second oral aldosterone antagonist available for the treatment of arterial hypertension and heart failure. Treatment with eplerenone has been associated with decreased blood pressure and improved survival for patients with heart failure and reduced left ventricular ejection fraction. Due to the selectivity of eplerenone for the aldosterone receptor, severe adverse effects such as gynecomastia and vaginal bleeding seem to be less likely in patients who take eplerenone than in those who take spironolactone. The most common and potentially dangerous side effect of spironolactone--hyperkalemia--is also observed with eplerenone but the findings from clinical trials do not indicate more hyperkalemia induced drug withdrawals. Treatment with eplerenone should be initiated at a dosage of 25mg once daily and titrated to a target dosage of 50mg once daily preferably within 4 weeks. Serum potassium levels and renal function should be assessed prior to initiating eplerenone therapy, and periodic monitoring is recommended, especially in patients at high risk of developing hyperkalemia.

A retrospective multicenter study on long-term prevalence of chronic pain after cardiac surgery.

BACKGROUND: There are limited data on sternotomy as a cause of chronic postsurgical pain, mainly restricted to 1 year after surgery. AIMS: To assess the prevalence of chronic post-sternotomy pain and its interference on daily living. METHODS: In three groups of patients, a standardized telephone interview was obtained at 3 months (n = 313), 1 year (n = 313), and 3 years (n = 319) following the rehabilitation program after cardiac surgery, in 11 rehabilitation centers. Presence, site, and the severity and interference of pain on selected daily living items were assessed. RESULTS: The prevalence of pain after cardiac surgery was 35.3% in the 3-month group, 26.8% in the 1-year group, and 19.8% in the 3-year group (P < 0.0001). Pain in the 3-year group was rated as moderate to severe in one-third of the patients. In patients aged above 75 years, the prevalence of pain in the 3-month and the 3-year group was nonsignificantly different [34.2 and 29.3%, respectively (NS)]. In the 3-month group, pain was more frequent in the female (51.4%) than in the male patients (31.3%; P < 0.01); in the remaining groups, a comparable prevalence was documented. CONCLUSION: Results form this large, retrospective, multicenter survey indicated that one out of five patients still complain pain at 3 years after cardiac surgery; persistence of pain was more common in the older patients. The approach to management of chronic pain by cardiologists and cardiac surgeons should be improved.

Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in stable patients with coronary artery disease treated with dual antiplatelet therapy : The ROMAN (RanOlazine vs. aMlodipine on platelet reactivity in stable patients with CAD treated with dual ANtiplatelet therapy) study.

Amlodipine, commonly used for relief of ischemic symptoms in coronary artery disease (CAD), may affect clopidogrel-induced antiplatelet effects. It remains unknown if ranolazine, an antianginal drug that constitutes a pharmacologic alternative to calcium channel blockade, interferes with clopidogrel-induced antiplatelet effects. The aim of the ROMAN study was to compare the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in clopidogrel treated patients with CAD. A prospective, randomized, cross-over, open-label study conducted in a total of 210 CAD patients on aspirin (100 mg/q.d.) and clopidogrel (75 mg/q.d.) 1 month following percutaneous coronary intervention. Patients were randomly assigned to amlodipine (10 mg p.d., n = 105) or ranolazine (750 mg b.i.d., n = 105) for 15 days, and after a 1-week wash-out period, crossed-over treatment for 15 days. P2Y12 reaction units (PRU) were assessed at baseline and after each treatment sequence. High on-treatment platelet reactivity (HPR) was defined as a PRU > 208. Amlodipine was associated with higher PRU than ranolazine (182 ± 75 vs. 167 ± 64, p = 0.028). As compared with baseline, PRU increased significantly after treatment with amlodipine (p = 0.018), but was not different after ranolazine therapy (p = 0.871). Changes in platelet reactivity following amlodipine therapy appeared to depend on baseline HPR status, as PRU levels significantly increased only among HPR subjects. In stable CAD patients treated with dual antiplatelet therapy after PCI, concomitant treatment with amlodipine, but not ranolazine, interferes with clopidogrel-induced antiplatelet effects.