Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM).

The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended.

Influence of atrial fibrillation subtypes on anticoagulant therapy in a high-risk older population: the FAI project.

BACKGROUND AND AIM: Benefits of oral anticoagulants (OAC) in atrial fibrillation (AF) patients with moderate-to-high risk of stroke are independent of AF pattern. We evaluated whether AF clinical subtype influenced OAC use in a representative sample of the Italian older population. METHODS: A cross-sectional examination of all subjects aged 65 + years from three general practices in northern, central, and southern Italy started in 2016. A double-screening procedure was followed by clinical and ECG confirmation. Patients were categorized as having paroxysmal, persistent, or permanent AF. OAC use was evaluated in confirmed AF patients. RESULTS: The sample included 6016 subjects. Excluding 235 non-eligible, participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Overall, 319 AF cases were identified: 43.0% had paroxysmal, 21.3% persistent, and 35.7% permanent AF. Frequency of OAC therapy was 91.2% in permanent, 85.3% in persistent, and only 43.0% in paroxysmal AF (P < 0.001). In multivariate analysis, controlled for baseline variables and risk scales, persistent and permanent AF were associated with a significant increase in the likelihood of receiving OAC compared with paroxysmal AF (P < 0.001). This was confirmed for permanent AF also in multivariate analyses considering separately vitamin K antagonists or direct-acting oral anticoagulants (OR, 4.37, 95% CI, 2.43-7.85; and 1.92, 95% CI, 1.07-3.42, respectively) and for persistent AF and direct-acting oral anticoagulants (OR, 4.33, 95% CI, 2.30-8.15). CONCLUSIONS: In a population-based survey, AF pattern was an independent predictor of OAC treatment. Paroxysmal AF is still perceived as carrying a lower risk of vascular events.

Routine assessment of cognitive function in older patients with hypertension seen by primary care physicians: why and how-a decision-making support from the working group on 'hypertension and the brain' of the European Society of Hypertension and from the European Geriatric Medicine Society.

: The guidelines on hypertension recently published by the European Societies of Hypertension and Cardiology, have acknowledged cognitive function (and its decline) as a hypertension-mediated organ damage. In fact, brain damage can be the only hypertension-mediated organ damage in more than 30% of hypertensive patients, evolving undetected for several years if not appropriately screened; as long as undetected it cannot provide either corrective measures, nor adequate risk stratification of the hypertensive patient.The medical community dealing with older hypertensive patients should have a simple and pragmatic approach to early identify and precisely treat these patients. Both hypertension and cognitive decline are undeniably growing pandemics in developed or epidemiologically transitioning societies. Furthermore, there is a clear-cut connection between exposure to the increased blood pressure and development of cognitive decline.Therefore, a group of experts in the field from the European Society of Hypertension and from the European Geriatric Medicine Society gathered together to answer practical clinical questions that often face the physician when dealing with their hypertensive patients in a routine clinical practice. They elaborated a decision-making approach to help standardize such clinical evaluation.

Prevalence of Atrial Fibrillation Subtypes in Italy and Projections to 2060 for Italy and Europe.

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) subtypes may carry different cardiovascular risk profiles, but information on their frequency from population-based studies is lacking. We estimated prevalence of AF subtypes in a representative sample of the Italian older population, projecting figures for Italy and the European Union. DESIGN: Cross-sectional study. SETTING: Three primary care practices in northern, central, and southern Italy. PARTICIPANTS: All individuals aged 65 years or older, for a total sample of 6,016 subjects. Excluding 235 noneligible, participation was 78.3%, which left 4,528 participants. MEASUREMENTS: A double systematic and opportunistic screening procedure identified possible AF cases, followed by clinical and electrocardiogram confirmation. Patients were categorized with paroxysmal, persistent, or permanent AF. Prevalence was calculated by sex and 5-year age groups. Prevalence figures were applied to population projections for all 28 European Union states to estimate AF subtypes expected in future decades. RESULTS: In the 4,528 participants (mean age = 74.5 ± 6.8 years; 47.2% men), 331 AF cases were identified: 140 (42.3%) paroxysmal, 77 (23.3%) persistent, and 114 (34.4%) permanent. Prevalence was 3.1% (95% confidence interval (CI) = 2.6%-3.6%) for paroxysmal, 1.7% (95% CI = 1.4%-2.1%) for persistent, and 2.5% (95% CI = 2.1%-3.0%) for permanent AF. Italian older persons having AF in 2016 were estimated at approximately 449,000 for paroxysmal, approximately 240,000 for persistent, and approximately 391,000 for permanent AF, projected to increase in 2060 to approximately 785,000, approximately 358,000, and approximately 748,000, respectively. European Union older persons having AF in 2016 were estimated at approximately 3,185,000 for paroxysmal, approximately 1,722,000 for persistent, and approximately 2,710,000 for permanent AF, projected to increase in 2060 to approximately 5,989,000, approximately 2,833,000, and approximately 5,579,000, respectively. CONCLUSION: We provided first projections of AF subtypes for Italy and Europe. The worse cardiovascular risk profile of persistent and permanent forms indicates an increased burden in future decades.

Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project.

AIMS: To estimate prevalence of atrial fibrillation (AF) in a representative sample of the Italian elderly population, projecting figures for Italy and the European Union. METHODS AND RESULTS: A cross-sectional examination of all subjects aged 65+ years from three general practices in Northern, Central, and Southern Italy started in 2016. Participants were administered a systematic and an opportunistic screening, followed by clinical and electrocardiogram confirmation. The study sample included 6016 subjects. Excluding 235 non-eligible, among the remaining 5781 participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Prevalence of AF was 7.3% [95% confidence intervals (CI) 6.6-8.1], higher in men and with advancing age (6.6% from systematic plus 0.7% from opportunistic screening). Using prevalence figures, Italian elderly having AF in 2016 were estimated at ∼1 081 000 (95% CI 786 000-1 482 000). Considering stable prevalence, this number will increase by 75% to ∼1 892 000 in 2060 (95% CI 1 378 000-2 579 000). European Union elderly having AF in 2016 were estimated at ∼7 617 000 (95% CI 5 530 000-10 460 000), increasing by 89% to ∼14 401 000 in 2060 (95% CI 10 489 000-19 647 000). In 2016, subjects aged 80+ years represented 53.5% of cases in Italy and 51.2% in the European Union; in 2060, 69.6% and 65.2%, respectively. CONCLUSIONS: Our findings indicate a high burden of AF in coming decades, especially among the oldest-old, who carry the higher AF-related risk of stroke and medical complications.

Blood pressure in acute ischemic stroke: challenges in trial interpretation and clinical management: position of the ESH Working Group on Hypertension and the Brain.

: Altered blood pressure (BP) is a common phenomenon in acute ischemic stroke (AIS), with high BP being the most frequent scenario. The pathophysiology of BP changes in AIS is complex and only partially understood. The available evidence indicates that extremely high BP during AIS is associated with a poor outcome. Importantly, the observed relationship between BP and stroke outcome may or may not be causally related. Higher baseline BPs in focal cerebral ischemia may indicate preexisting hypertension, but may also be an effect of both nonspecific and stroke-related factors. Although antihypertensive therapy effectively reduces BP in AIS, studies on early BP lowering in AIS produce conflicting results in terms of functional outcome and mortality. Systematic reviews on BP management in AIS did not result in clinically applicable conclusions in general. However, the investigation on the effect of BP and its alterations in AIS are hampered by various important methodological issues. This position statement was prepared by a group of experts from the European Society of Hypertension and invited neurologists to discuss the main reasons for the discrepancies in the current evidence on the prognosis and treatment of altered BP in AIS which should be taken into account in future studies.

How to Improve Effectiveness and Adherence to Antihypertensive Drug Therapy: Central Role of Dihydropyridinic Calcium Channel Blockers in Hypertension.

Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.

An update of the Italian Stroke Organization-Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: A personalized medicine approach.

Although proof-based medicine has generated much valid evidence for the drawing up of guidelines and recommendations for best clinical practice in symptomatic and asymptomatic carotid stenosis, whether and when it is better to employ endarterectomy or stenting as the intervention of choice still remain matters of debate. Moreover, guidelines have been targeted up to now to the 'representative' patient, as resulting from the statistical analyses of the studies conducted on the safety and efficacy of both interventions as well as on medical therapy alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness Diffusion (SPREAD) group has thus decided to update its statements for an 8th edition. To this end, a multidisciplinary team of authors representing Italian scientific societies in the neurology, neuroradiology, vascular and endovascular surgery, interventional cardiology, and general medicine fields re-examined the literature available on stroke. Analyses and considerations on patient subgroups have allowed to model the risks/benefits of endarterectomy and stenting in the individual. Accordingly, the guideline's original methodology has been revised to follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like approach, integrating it with new considerations on Precision, or Personalized Medicine. Therefore, this guideline offers recommendations on precision medicine for the single patient, and can be followed in addition to the more standard guidelines.

Carotid artery stenting: second consensus document of the ICCS/ISO-SPREAD joint committee.

BACKGROUND: A major debate in cerebrovascular medicine today is over the choice of the best treatment to implement for stenosis of the carotid artery. Carotid artery stenting is a less invasive technique than endarterectomy for the treatment of carotid stenosis, and is becoming more widely performed, particularly on patients with carotid artery stenosis who present also with comorbidities. To address the aspects related to the use of carotid artery stenting, an Italian multidisciplinary task force comprising the most representative scientific societies concerned with carotid artery disease was set up to provide neurologists, radiologists, cardiologists, vascular surgeons, and all those involved in stroke prevention and treatment with an updated, evidence-based consensus document. SUMMARY: The task force followed a structured methodology to assess the literature on carotid stenosis in order to provide a summary of the main issues related to carotid artery stenting, including the definition of the grade of symptomatic carotid artery stenosis, indications for intervening on the carotid artery stenosis, establishing whether to perform either a surgical or an endovascular procedure, the training, credentialization, and competency needed by physicians to perform carotid artery stenting, acceptable complication rates and risk certification for carotid artery stenting, management of stented patients, durability of carotid artery stenting, and future tasks. Here, we outline the main findings of this effort. KEY MESSAGES: As for any guideline or consensus statement, each point is valid as long as the evidence on which it is based remains up to date. In a fast-evolving field of medicine such as that of carotid artery stenosis management, and in particular carotid artery stenting, the stimulation of continuous and fruitful discussion among all professionals involved is mandatory. We hope that this document may provide a standardized basis for the application of carotid artery stenting as implemented today.

An update on Italian Stroke Organization guidelines on carotid endarterectomy and stenting.

One hundred and fifty-three authors, 45 Italian scientific societies, and two Italian patients' associations participated in drafting the Italian Stroke Organization document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of the Italian Stroke Organization document, the main trials on carotid endoarterectomy and stenting were critically reviewed in order to formulate recommendations for these procedures. Recommendations are presented here for the referral of patients to either carotid endarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic.

Body mass and osteoarthritic pain: results from a study in general practice.

OBJECTIVES: To define the relationship between BMI and pain due to osteoarthritis (OA) of the hand, hip, and knee in patients seen in general practice; to evaluate if overweight is related to co-morbidity and education, and influences the prescription patterns of GPs. METHODS: 2,764 Italian GPs recruited 10 consecutive patients with symptomatic OA, diagnosed according to the ACR criteria. Pain intensity on a visual analogue scale, BMI, years of formal education, comorbidities, pharmacological and non-pharmacological interventions, and referral to specialists were recorded. RESULTS: The most painful joints were the knee in 12,827 patients (53.6%), the hip in 5,645 (23.6%), and the hand in 5,467 (22.8%). A BMI indicative of overweight or obesity was found in 74.8% of men and in 68.3% of women. Mean BMI was higher in knee OA (27.9±3.9), in generalised OA (27.5±4.2), and hip OA (27±3.7) than in hand OA (25.5±3.4). The prevalence of obesity for hip and knee OA was higher than that reported for the general Italian population. Obesity was an important risk factor for pain in all OA localisations. Co-morbidities and lower education were associated with obesity and more intense pain (p<0.0001). Obesity and overweight were less frequent in institutionalised patients. CONCLUSIONS: Our study confirms that more than two thirds of Italian patients with symptomatic OA seen by GPs are overweight or obese. Obesity is clearly associated with OA pain, a finding which is probably underestimated by GPs who are not used to modulate treatment and specialist referral according to patients' BMI.

Stroke-Unit and emergency medical service: a 48-month experience in northern Italy.

Since the therapeutic window for acute ischaemic stroke is very short, early arrival at emergency care rooms is mandatory. Emergency medical service (EMS), assuring fast patients transportations, plays a fundamental role in the management of stroke. We have prospectively analysed the utilisation of EMS in the management of stroke patients in a countryside area of northern Italy. Among patients presenting with an acute stroke during the period January 2007-December 2010, those with an ascertained time of onset and documented ongoing brain ischaemia at neuroimaging were included in the study. For all of those patients, the personal data, means of arrival, nature of stroke, whether first stroke or recurrence, severity of stroke and the in-hospital outcome were recorded. Of 1,188 patients hospitalised with a definite diagnosis of stroke, 757 patients were included in the study. Of those, 285 patients (37.6 %) were transported by EMS. EMS allowed earlier admissions (75 % within 3 h of stroke onset), but also transportation of patients of an older age (75 vs. 71 years, p < 0.001), and with more severe strokes (62 % of total anterior circulation infarctions). Our study confirms that EMS is essential in delivering the earliest therapy to patients with acute cerebral infarction living in an extra-urban area of northern Italy. However, work is needed in optimising EMS, since transported patients are often not prone to therapy.

Atherothrombotic burden and medium-term prognosis in patients with acute ischemic stroke: findings of the SIRIO study.

BACKGROUND: Short- and medium-term mortality after acute stroke is related to the severity of the index event and the patient's age. However, recent studies have reassessed the prognostic value of the systemic atherothrombotic burden in these patients, not only in the long term. This post hoc analysis of the findings of the SIRIO trial (Stroke in Italy and Related Impact on Outcome) examined the prognostic impact of systemic atherothrombosis. METHODS: SIRIO was a multicenter observational study enrolling patients during the acute phase of stroke of both ischemic and hemorrhagic origin. The present analysis, however, only covered patients with ischemic stroke. At baseline, the main personal and clinical details were recorded and patients were classified as having either polyvascular disease or single arterial disease on the basis of whether they had symptomatic atherothrombotic disease in other sites besides the cerebrovascular location. For all patients we calculated the Essen Stroke Risk Score (ESRS), dividing them into groups with scores of less than 3 or 3 and more. We recorded total mortality and nonfatal vascular events 12 months after enrolment. Multivariate logistic regression analysis was used to select predictors of medium-term mortality and nonfatal cardiovascular events. There were 2,561 patients with ischemic stroke, 823 of them classified as having polyvascular disease; 940 (out of 2,485) had an ESRS of less than 3 and 1,545 had a score of 3 or more. RESULTS: The combined endpoint 'death (all causes) and nonfatal cardiovascular events within 12 months of hospital discharge' was significantly dependent on the following factors: ESRS, Rankin scale and National Institutes of Health Stroke Scale scores, and polyvascular disease. Polyvascular disease status significantly affected mortality and nonfatal cardio- and cerebrovascular events after discharge (OR = 1.44, 95% CI = 1.10-1.88). Age was also confirmed as a significant predictor of the combined endpoint. CONCLUSIONS: Besides age and the clinical severity of the index event, symptomatic involvement of several vascular districts was also an important predictor of mortality and nonfatal cardiovascular events in the medium term in patients with ischemic stroke.

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.

Effect of prior medical treatments on ischemic stroke severity and outcome.

Antiplatelets, antihypertensives, and statins might reduce the severity of the event or improve outcome in patients who, despite prior medical treatment, have a stroke. We evaluated, in patients who had an ischemic stroke, the effect, on stroke severity and outcome, of prior treatment with antiplatelets, antihypertensives, and statins, used either alone or in a three-drug combination. Stroke in Italy and Related Impact on Outcome (SIRIO) was a prospective, nationwide, multicenter, hospital-based, observational study that included patients aged.18 years with acute ischemic stroke. We studied 2,529 acute ischemic stroke patients from the SIRIO population: 887 were antiplatelet users, 1,497 antihypertensive users, 231 statin users, and 138 three-drug combination users prior to the index event. The adjusted logistic regression analysis showed an association between prior treatment with statins and good functional outcome at discharge, while prior treatment with antiplatelets, antihypertensives or the three-drug combination did not influence severity or outcome. The absolute probability of a good functional outcome was 46.3% (95% CI: 40.3%-53.2%) in statin users and 36.7% (95% CI: 34.7%-38.7%) in non-users of statins; the absolute risk difference was 9.6% (95% CI: 2.9%-16.4%; p=0.004). Prior treatment with antiplatelets, antihypertensives, or the three-drug combination did not influence stroke severity or outcome, while prior treatment with statins did not influence stroke severity but was associated with a better functional outcome.

Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients.

BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD). METHODS: This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and established CHD who were taking a stable daily dose of simvastatin 20 mg. Patients were randomized to ezetimibe/simvastatin 10/20 mg (eze/simva; n = 56) or simvastatin 40 mg (simva; n = 56) for 6 weeks. Percent change from baseline in LDL-C, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were assessed by use of the Student t test. The percent of patients achieving LDL-C less than 100 mg/dL (<2.6 mmol/L) or less than 80 mg/dL (<2.0 mmol/L) was analyzed via logistic regression with terms for treatment, baseline LDL-C, age, and gender. RESULTS: Baseline characteristics were similar between groups. Treatment with eze/simva combination resulted in significantly greater reductions in LDL-C, total cholesterol, and triglycerides versus doubling the dose of simva to 40 mg (all P < .01). Significantly more patients achieved LDL-C less than 100 mg/dL (<2.6 mmol/L) and less than 80 mg/dL (<2.0 mmol/L) with ezetimibe/simvastatin versus doubling the dose of simva to 40 mg (73.2% vs 25.0%; P < .001) for simvastatin. Changes in HDL-C were similar between treatments. Both treatments were generally well tolerated. CONCLUSION: In high-risk CHD patients with hypercholesterolemia, treatment with eze/simva combination resulted in significantly greater reductions in LDL-C, total cholesterol and triglycerides, as well as greater achievement of recommended LDL-C targets, compared with doubling the simvastatin dose to 40 mg over the 6-week period. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00423579).

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.

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

BACKGROUND: Treatment 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. METHODS: Data 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 (> or = 65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable). RESULTS: EZ/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. CONCLUSION: EZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy. TRIAL REGISTRATION: Clinical trial registration numbers: NCT00423488 and NCT00423579.