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Angeli F.,Struttura Complessa di Cardiologia | Mazzotta G.,University of Perugia | Reboldi G.,University of Perugia
Current Vascular Pharmacology

The combined use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) poses a dilemma to clinicians. On the one hand, indirect evidence from compelling, but still surrogate outcome measures such as blood pressure and proteinuria suggest some merits of this combination. On the other hand, the outcome benefits of the ACEIs+ARBs combination in morbidity/mortality trials remain confined to patients with severe congestive heart failure (CHF) and reduced ejection fraction. Incidentally, most of the benefit offered by the ACEIs+ARBs combination in these patients was not driven by mortality, but by fewer rehospitalizations for CHF. Even in patients with renal disease and proteinuria, the combined use of ACEIs and ARBs, although highly effective in reducing urinary protein excretion, has not yet been proven to significantly delay end-stage renal disease and the need for dialysis. In the Ongoing Telmisartan Alone and In Combination With Ramipril Global Endpoint Trial (ONTARGET), the dual blockade of the renin angiotensin system did not produce additional outcome benefit over that afforded by ACE inhibition alone. Notably, however, patients with BP >160/100 mmHg at entry were excluded from ONTARGET, thus limiting the applicability of these results to the treatment of hypertension. The European Society of Hypertension guidelines do not suggest large-scale use of the ACEIs+ARBs combination in patients with hypertension. However, patients with resistant hypertension, particularly if proteinuria coexists, could benefit from this combination, which however requires close monitoring for adverse events, including hyperkalemia and worsening renal function. © 2010 Bentham Science Publishers Ltd. Source

Zaca V.,U.O.C. Cardiologia Ospedaliera | Marcucci R.,University of Florence | Parodi G.,Cardiologia Invasiva | Limbruno U.,U.O. Cardiologia | And 3 more authors.

The aim of this review is to formulate practical recommendations for the management of antithrombotic therapy in patients undergoing cardiac implantable electronic device (CIED) surgery by providing indications for a systematic approach to the problem integrating general technical considerations with patient-specific elements based on a careful evaluation of the balance between haemorrhagic and thromboembolic risk. Hundreds of thousands patients undergo implantation or replacement of CIEDs annually in Europe, and up to 50% of these subjects receive antiplatelet agents or oral anticoagulants. The rate of CIED-related complications, mainly infective, has also significantly increased so that transvenous lead extraction procedures are, consequently, often required. Cardiac implantable electronic device surgery is peculiar and portends specific intrinsic risks of developing potentially fatal haemorrhagic complications; on the other hand, the periprocedural suspension of antithrombotic therapy in patients with high thromboembolic risk cardiac conditions may have catastrophic consequences. Accordingly, the management of the candidate to CIED surgery receiving concomitant antithrombotic therapy is a topic of great clinical relevance yet controversial and only partially, if at all, adequately addressed in evidence-based current guidelines. In spite of the fact that in many procedures it seems reasonably safe to proceed with aspirin only or without interruption of anticoagulants, restricting to selected cases the use of bridging therapy with parenteral heparins, there are lots of variables that may make the therapeutic choices challenging. The decision-making process applied in this document relies on the development of a stratification of the procedural haemorrhagic risk and of the risk deriving from the suspension of antiplatelet or anticoagulant therapy combined to generate different clinical scenarios with specific indications for optimal management of periprocedural antithrombotic therapy. © The Author 2015. All rights reserved. Source

De Maria R.,CNR Institute of Clinical Physiology | Bohm M.,Kardiologie Angiologie und Internistische Intensivmedizin Universitatsklinikum Es Saarlandes | Ponikowski P.,Klinika Kardiologii | Filippatos G.,National and Kapodistrian University of Athens | And 6 more authors.
International Journal of Cardiology

Background: Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients. Methods: We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome. Results: Median age was 69 years, 35.8% were female, 20.6% had a normal ejection fraction, and 65% had at least one comorbidity. During 5861 person-years follow-up, 12.1% of the patients met the study end-point of all-cause death (n = 750) or urgent transplantation (n = 9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction < 20%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort. Conclusions: The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice. © 2011 Elsevier Ireland Ltd. Source

Verdecchia P.,Clinical Research Unit Preventive Cardiology | Angeli F.,Struttura Complessa di Cardiologia | Mazzotta G.,Struttura Complessa di Cardiologia | Martire P.,Struttura Complessa di Cardiologia | And 3 more authors.
Therapeutic Advances in Cardiovascular Disease

Aliskiren is an orally active direct renin inhibitor which inhibits the synthesis of angiotensin I by linking to active renin on a deep cleft of its molecular structure, the site of hydrolysis of the Leu10-Val11 bond of angiotensinogen. At variance with angiotensin-converting enzyme (ACE) inhibitors, aliskiren eliminates the main substrate for the 'escapeg' phenomenon (synthesis of angiotensin II from angiotensin I through alternative enzymatic pathways). The possibility that the antihypertensive effect of aliskiren differs from that of ACE inhibitors needs to be proved in specifically designed clinical trials. Over the past 2 years, three studies have been published which directly compared aliskiren with ramipril, in patients with hypertension. We made a pooled analysis of these studies. In order to avoid interference with additional drugs, analysis was restricted to trial periods when the two drugs were given as monotherapy. In each individual study, systolic blood pressure (BP) was slightly lower with aliskiren. Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mmHg; fixed effect model; p < 0.0001; and 1.87 mmHg; random effect model; p = 0.0055). The standardized mean difference between the treatments was 2.58 (fixed effect model; p < 0.0001) and 2.92 (random effect model; p = 0.0017) in favor of aliskiren. Compared with ramipril, aliskiren may have induced a more complete 'upstreamg' inhibition of the rening-angiotensing- aldosterone system, with consequent greater suppression of angiotensin II. Another potential explanation may be the longer terminal elimination halflife of aliskiren (about 40 hours) compared with ramiprilat (13g-17 hours). These data provide further evidence that aliskiren monotherapy provides a sustained BP reduction over the 24 hours. © 2010 The Author(s). Source

Verdecchia P.,Struttura Complessa di Cardiologia | Angeli F.,Struttura Complessa di Cardiologia | Mazzotta G.,Struttura Complessa di Cardiologia | Ambrosio G.,University of Perugia | Reboldi G.,University of Perugia
Hypertension Research

Angiotensin II receptor blockers (ARBs) are widely used in the treatment of patients with hypertension, heart failure, diabetic nephropathy and other clinical conditions. Several intervention trials and systematic overviews showed that both angiotensin-converting enzyme inhibitors and ARBs effectively reduce the risk of stroke, myocardial infarction and congestive heart failure in hypertensive patients. Two recent intervention trials conducted in Japan (JIKEI and Kyoto studies) suggested that the protective effect of ARBs on major cardiovascular events might be partly independent from the degree of blood pressure (BP) reduction. Both studies used a prospective randomized open blinded end point (PROBE) design. No significant differences emerged in both studies between the ARB group (valsartan) and the control group in the achieved BP. We made a pooled analysis of the JIKEI and Kyoto studies. Overall, valsartan significantly reduced the risk of the primary composite outcome (by 42%; P<0.0001), angina pectoris (by 38%; P<0.0001), heart failure requiring hospitalization (by 43%; P=0.013) and cerebrovascular events (by 42%; P=0.002). The protective effect on the dissecting aneurysm of aorta bordered statistical significance. These data reinforce the notion that the protective effect of angiotensin II inhibition is partly independent of BP reduction. © 2010 The Japanese Society of Hypertension All rights reserved. Source

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