A proposal for the idea of a flexible-combination polypill in arterial hypertension

Objective: Modern pharmaceutical strategies in arterial hypertension, as well as in other fields, are directed toward two major apparently contrasting objectives: 1) sim- plification of treatment by grouping multiple drugs into single fixed-combination pharmaceutical units (including “polypill”) to improve patient adherence, and 2: personalization of therapy to tailor treatments according to specific individual aspects including pharmacogenomics. The combined fulfillment of these objectives would conceivably entail the unre- alistic development of a very great variety of fixed-combination polypills, each different for drug composition and dosage. An alternative view that could combine the need for both therapy simplification and personalization may be the concept of a flexible-combination polypill. Design and Methods: In order to test this approach, we are devising a preliminary study aimed to assess the feasibility and efficacy of shifting individual patients’ treatment from multiple daily administration (multi-administration) to a single once-a-day administration (mono-administration) of the same drugs. After approval of Ethical Committee, a cross-over randomized study will be carried out for 24 weeks in 52 well controlled non complicated hypertensive outpatients under multiple therapy with at least one hypotensive drug and/or a statin and/or aspirin. Each subject will remain for an 8 weeks period on multi-administration and for another 8 weeks period on mono-administration of the same therapy; the two peri- ods will be separated by 8 weeks to avoid a carry-over effect and their sequence will be randomized

Zofenopril: Blood pressure control and cardio-protection

Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardioprotective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes

Pitfalls in the Measurement of the Nocturnal Blood Pressure Dip in Adolescents with Type 1 Diabetes

OBJECTIVE—The purpose of this study was to screen adolescents with type 1 diabetes using ambulatory blood pressure monitoring (ABPM) to 1) test the hypothesis that using a preset sleep time results in an overdiagnosis of abnormal nocturnal dipping in systolic blood pressure and 2) assess the reproducibility of an abnormal nocturnal systolic blood pressure dip

Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH)

No abstract available

Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes

AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] 200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] 200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925

Gender differences in the association between education and the incidence of cardiovascular events in Northern Italy.

Background: The educational differences in the incidence of major cardiovascular events are under-studied in Southern Europe and among women. Methods: The study sample includes n\u2009=\u20095084 participants to 4 population-based Northern Italian cohorts, aged 35-74 at baseline and with no previous cardiovascular events. The follow-up to ascertain the first onset of coronary heart disease (CHD) or ischaemic stroke ended in 2002. At baseline, major cardiovascular risk factors were investigated adopting the standardized MONICA procedures. Two educational classes were obtained from years of schooling. Age- and risk factors-adjusted hazard ratios of first CHD or ischaemic stroke were estimated through sex-specific separate Cox models (high education as reference). RESULTS: Median follow-up time was 12 years. Event rates were 6.38 (CHD) and 2.12 (ischaemic stroke) per 1000 person-years in men; and 1.59 and 0.94 in women. In men, low education was associated with higher mean Body Mass Index and prevalence of diabetes and cigarette smokers; but also with higher HDL cholesterol and a more favourable alcohol intake pattern. Less-educated women had higher mean systolic blood pressure, Body Mass Index and HDL cholesterol and were more likely to have diabetes. Men and women in the low educational class had a 2-fold increase in ischaemic stroke and CHD incidence, respectively, after controlling for major risk factors. Education was not associated with CHD incidence in men. Higher ischaemic stroke rates were observed among more educated women. Conclusion: In this northern Italian population, the association between education and cardiovascular risk seems to vary by gender

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alon

Uric acid and xantine-oxidase inhibitors in patients with gout: A re-assessment and an update

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Influence of the gender on the relationship between heart rate and blood pressure

Blood Pressure (BP) and Heart Rate (HR) provide information on clin-ical condition along 24h. Both signals present circadian changes due to sympa-thetic/parasympathetic control system that influence the relationship between them. Moreover, also the gender could modify this relation, acting on both con-trol systems. Some studies, using office measurements examined the BP/HR re-lation, highlighting a direct association between the two variables, linked to sus-pected coronary heart disease. Nevertheless, till now such relation has not been studied yet using ambulatory technique that is known to lead to additional prog-nostic information about cardiovascular risks. In order to examine in a more ac-curate way this relation, in this work we evaluate the influence of gender on the BP/HR relationship by using hour-to-hour 24h ambulatory measurements. Data coming from 122 female and 50 male normotensive subjects were recorded using a Holter Blood Pressure Monitor and the parameters of the linear regression fit-ting BP/HR were calculated. Results confirmed those obtained in previous stud-ies using punctual office measures in males and underlined a significant relation between Diastolic BP and HR during each hour of the day in females; a different trend in the BP/HR relation between genders was found only during night-time. Moreover, the circadian rhythm of BP/HR is similar in both genders but with different values of HR and BP at different times of the day