Assisi Foundation of Memphis

BACKGROUND In the increasing progress of scientific knowledge, every new discovery is a basis for new problems. In fact, after the success of Angiotensin-Converting Enzyme (ACE)-inhibitors in different cardiovascular diseases, the evidence of the “escape” of ACE and the discovery of Angiotensin- Receptor Blockers (ARBs) became the basis for a new question: is a dual blockade of the Renin-Angiotensin System (RAS) correct? DISCUSSION The different trials carried out (also the latest ONTARGET) didn’t give reliable answers, because differences were found both in the various diseases (hypertension, heart failure, coronary disease, nephropathy, diabetic or not), and between the single drugs of the class. We can say that this combination treatment didn’t show reliable clinical efficacy yet, except in heart failure and in some subgroups of hypertensive patients, checking carefully serum electrolytes and renal function. But even though we haven’t got certain outcomes, the research goes on quickly and some other sites of modulation of RAS were identified, from its first phases (aliskiren as prototype of direct renin inhibitors).

Introduction: Azilsartan medoxomil is a newly approved angiotensin-receptor blocker for the management of hypertension. It is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective angiotensin-receptor blocker with estimated bioavailability of ∼ 60%. This new agent induces a potent and long-lasting antihypertensive effect. The effective therapeutic antihypertensive dosages of azilsartan medoxomil in humans vary from 40 to 80 mg/day.Areas covered: The authors review the results of clinical trials published in journals indexed in Medline, Scopus and Google Scholar. Primarily the authors discuss articles that analyze the safety and efficacy of azilsartan in lowering blood pressure.Expert opinion: Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.

An inappropriately high left ventricular mass (iLVM) may be detected in patients with diabetes mellitus. Several hemodynamic and nonhemodynamic factors stimulating LVM growth may actively operate in these patients. In this study, we assessed prevalence and factors associated with iLVM in patients with diabetes mellitus. We analyzed baseline data from 708 patients (61 ± 7 years, 57% treated for hypertension) with type 2 diabetes mellitus without evidence of cardiac disease enrolled in the left ventricular dysfunction in diabetes study. iLVM was diagnosed by Doppler echocardiography as LVM more than 28% of the expected LVM predicted from height, sex and stroke work. iLVM was detected in 166 patients (23%), irrespective of concomitant hypertension. Patients with iLVM were more frequently women, had higher BMI and prevalence of metabolic syndrome, higher serum triglyceride levels and were treated more frequently with metformin and diuretics. In a multivariate model, female sex [odds ratio (OR) 1.502 (95% confidence interval (CI) 1.010-2.231), P = 0.04], higher serum triglyceride levels [OR 1.007 (95% CI 1.003-1.012), P < 0.001] and BMI [OR 1.220 (95% CI 1.116-1.335), P < 0.001] emerged independently related to iLVM. iLVM is detectable in about a quarter of patients with type 2 diabetes mellitus without evidence of cardiac disease and is unrelated to blood pressure levels. The association between LVM and some components of metabolic syndrome in these patients may have important practical implications.

Myocardial ischemia is a relatively frequent complication in patients undergoing non-cardiac surgery and β-blockers may have a protective effect. β-Blockers reduce the oxygen supply:demand ratio, and exert anti-inflammatory and anti-arrhythmic effects. However, randomized trials, specifically conducted to test this hypothesis, yielded conflicting results. The absolute risk for cardiac mortality and morbidity during and after non-cardiac surgery varies between patient groups defined by surgical risk categories, making it difficult to establish a risk:benefit ratio. We discuss the hypothesis that the protective effect of β-blockers on cardiovascular outcome differs across the different risk classes of surgical procedures, thereby explaining the conflicting evidence across studies. In particular, we examine the results of a recent meta-analysis that suggests that β-blockers may reduce mortality in patients undergoing high-risk non-cardiac surgery.