Augusto Zaninelli

Carotid Artery Stenting First Consensus Document of the ICCS-SPREAD Joint Committee

Background and Purpose— The prevention of stroke and the correct treatment of carotid artery stenosis represent today a major debate in cardiovascular medicine. Beside carotid endarterectomy, carotid angioplasty and stenting is becoming more widely performed for the treatment of severe carotid obstructive disease, and is now accepted as a less invasive technique that may provide an alternative for selected patients, particularly those with significant comorbidities. An Italian multidisciplinary task force, in which converged the most representative scientific societies involved in carotid treatment, was created to provide neurologists, radiologist, cardiologists, vascular surgeons, and all those involved in prevention and treatment of carotid disease with a simple, clear and updated evidence-based consensus document. Summary of Review— This First Consensus Document of the ICCS (Italian Consensus Carotid Stenting)/SPREAD group addressed the main issues related to methodology, definition of symptomatic and asymptomatic carotid stenosis, indication and procedures for carotid artery stenting, including the use of devices for preventing procedural embolic complications. Special attention was paid to credentials and competency for physicians qualifications to perform vascular angioplasty and stent placement, including training, acceptable complication rates and certification. Conclusions— As any guideline or consensus statement, also this document is valid as long as the evidence on which it is based remains up-to-date. In such a fast-evolving field of medicine as the management of carotid stenosis, it is mandatory to stimulate a continuous and fruitful discussion among all the professionals involved in this very evolutionary field.

The Prevalence of Diarrhea and Its Association With Drug Use in Elderly Outpatients: A Multicenter Study

OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients.METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS).RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 ± 6.2 yr, range 65–100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P= 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P= 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95–10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03–4.35), allopurinol (OR 2.19, 95% CI 1.26–3.81), psycholeptics (OR 1.82, 95% CI 1.26–2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01–2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08–1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders.CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

Upper gastrointestinal symptoms and therapies in elderly out-patients, users of non-selective NSAIDs or coxibs.

Background:  The association between coxib or non‐steroidal anti‐inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined.

Drug use by the elderly in general practice: effects on upper gastrointestinal symptoms

ObjectiveTo evaluate the prevalence of drug use by elderly outpatients in Italy and to identify the association between drug use and gastrointestinal symptoms.Study design and settingThe study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. All consenting elderly patients seen at the GPs’ offices were evaluated for gender, age, disability, current medications, and upper gastrointestinal symptoms.ResultsThe study included 5,515 elderly subjects. The prevalence of drug use was 91.6%, and the mean number of drugs taken was 2.86 per person. Both the prevalence and the mean number of drugs significantly increased with advancing age. Regarding gastrointestinal symptoms, 32.7% of patients reported at least one upper gastrointestinal symptom: 25% with indigestion syndrome, 16.2% with abdominal pain, and 14.2% with reflux symptoms. A significantly higher prevalence of symptoms was observed in females, patients who were taking a higher number of drugs, and those who had higher disability. Adjusted multivariate analysis demonstrated that the use of nonsteroidal antiinflammatory drugs, steroids, psycholeptics, diuretics, selective β2 adrenoreceptor agonists or adrenergics, and antiplatelet drugs was significantly associated with upper gastrointestinal symptoms.ConclusionThe prevalence of drug use is very high in this elderly outpatient population. The number of drugs and the use of some specific drug classes are significantly associated with the presence of upper gastrointestinal symptoms.

Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination.

The renin–angiotensin–aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

Metabolic syndrome: Diagnosis and clinical management, an official document of the Working Group of the Italian Society of Cardiovascular Prevention (SIPREC)

Metabolic syndrome (MS) is a complex clinical condition, characterised by a constellation of different metabolic and cardiovascular traits, typically high blood pressure, abdominal obesity, lipid profile abnormalities, insulin resistance and glucose intolerance. More recently, other features have been proposed; in particular, chronic proinflammatory and prothrombotic states seem to further characterise MS. Because of its multifactorial pathogenesis, a singular definition of this clinical condition is still debated, and physicians tend to make individual choices, e.g. the threshold for treatment initiation is heterogeneous. The lack of specific international guidelines, consisting of a diagnostic and therapeutic algorithm with an accurate cardiovascular risk stratification, makes the clinical management of patients with MS by primary physicians difficult and non-uniform. In particular, while there is convincing evidence that the progressive addition of components of MS increase cardiovascular risk, there are no consistent indications regarding treatment priorities and strategies.The Italian Society for Cardiovascular Prevention (Società Italiana di Prevenzione Cardiovascolare) [SIPREC], in the form of a panel of expert scientists operating in different areas of medicine, has compiled this consensus document in order to create a balanced and qualified document on the diagnosis and clinical management of MS. This document is focused on global risk-based stratification, aimed at identifying ‘low-risk’ and ‘high-risk’ patients within those presenting with MS. This approach may be particularly effective in clinical practice in identifying patients with MS with different degrees of cardiovascular disease risk profile. This approach may also be helpful to develop therapeutic strategies based on the global cardiovascular risk profile.

SPREAD‐STACI study: A protocol for a randomized multicenter clinical trial comparing urgent with delayed endarterectomy in symptomatic carotid artery stenosis

Rationale In patients with >50% carotid artery stenosis (as measured by North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria) suffering a transient ischemic attack or a minor ipsilateral stroke, carotid endarterectomy exerts maximum benefits, when performed within the first 15 days from the initial ischemic symptom. It is also known that the probability of a major stroke spikes within the first few days after a transient ischemic attack/minor stroke and then flattens out in the following days and weeks. It could be hypothesized that urgent carotid endarterectomy has greater benefit than delayed procedure. Aims Demonstrate that urgent carotid endarterectomy is more effective than delayed interventions. Design Centers employing neurolgist/stroke physicians and vascular surgeons will enroll TIA or minor stroke patients with >50 % carotid artery stenosis (Nascet criteria), randomized in two groups: urgent carotid endarterectomy (within 48 hours) and delayed carotid endarterectomy (operated between 48 hours and 15 days after onset of symptoms) Risk factors will be evaluated at enrollment. TIA will be classified by ABCD2 scoring system, and minor stroke by National Institutes of Health Stroke Scale (NIHSS) scores. The study will last 90 days per patient, starting from their initial symptom, and the follow-up will be performed by an indipendent neurologist. A total of 456 patients (228 / group) is needed to observe an absolute difference of 10% between groups. Outcomes Primary end-point is reduction in all types of stroke, AMI or death in urgent endarterectomy groupo compared to delayed ones. Secondary end-points are: Reduction of ipsilateral ischemic stroke in group 1 with respect to Group 2 Identification of predictive risk factors and Confirmation of no different rate for hemorragic/ischemiccomplications between groups.

Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes

BackgroundTreatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant.MethodsData were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (≥65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable).ResultsEZ/Simva treatment (N = 93) resulted in significantly greater reductions in LDL-C, TC, and TC/HDL-C ratio and higher attainment of LDL-C < 2.6 mmol/L vs doubling the simvastatin dose to 40 mg (N = 106). Study [including diabetic patients (OR = 2.9, p = 0.003)], EZ/Simva treatment (OR = 6.1, p < 0.001), and lower baseline LDL-C (OR = 0.9, p = 0.001) were significant positive predictors of LDL-C target achievement. When baseline LDL-C was expressed as a discrete variable, the odds of achieving LDL-C < 2.6 mmol/L was 4.8 in favor of EZ/Simva compared with Simva 40 mg (p < 0.001), regardless of baseline LDL-C level.ConclusionEZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy.Trial RegistrationClinical trial registration numbers: NCT00423488 and NCT00423579

The Stroke in Italy and Related Impact on Outcome (SIRIO) study: design and baseline data.

The SIRIO study collected detailed information on the stroke care of patients treated in neurological departments in Italy. This report refers to the baseline profile of patients. Each centre recorded the incident cases of ischaemic and haemorrhagic stroke, excluding SAH, for 1–4 months. Baseline data include demographics, risk factors, comorbidities, pre-event medications, social conditions, NIHSS and Rankin scale on entry, Barthel Index preevent, diagnostic tests and treatments applied on entry. Overall, 3018 patients (56.7% men; mean age 72.1±12.2 years) with ischaemic (85.3%) or haemorrhagic stroke were hospitalised in 103 centres; 51% arrived by ambulance. Median time to hospital was 140 min (RIQ: 60–615). TOAST classification of the 2573 ischaemic strokes was: 29.4% large-artery atherosclerosis, 24.6% cardioembolic, 26.2% small vessels occlusion, 6.5% other determined causes and 13.3% undetermined. CT and/or MR were performed in all patients. Total Greenfield’s comorbidity score was 5.4±3.5. Mean Barthel Index preevent was 93±17; Rankin score on entry was 4–5 in 48% of the patients and 0–1 in 25%. Mean NIHSS on entry was 7.1±5.4; 52% of the patients had a NHISS <6 and 1% >22. SIRIO began giving the expected insights on the in-hospital management of stroke in Italy. Further information will be provided by the longitudinal phase of the study, which is in progress. Pre-event patient management and mode of reporting call for additional educational actions.

Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update

The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.