Alice Vitagliano

Effects of ranolazine in symptomatic patients with stable coronary artery disease. A systematic review and meta-analysis.

BACKGROUND Ranolazine (R), as add-on therapy in symptomatic patients with chronic stable coronary artery disease (CAD), has been tested in randomized clinical studies. Aim of the study was to assess in a meta-analysis the effects of R on angina, nitroglycerin consumption, functional capacity, electrocardiographic signs of ischemia and hemodynamic parameters in patients with chronic CAD. METHODS Randomized trials assessing the effects of R compared to control on exercise duration, time to onset of angina, time to 1mm ST-segment depression, weekly nitroglycerin consumption and weekly angina frequency were included in the analysis. The effects of R compared to control on heart rate and blood pressure were also analyzed. RESULTS Six trials enrolling 9223 patients were included in the analysis. At trough and peak levels, R compared to control significantly improved exercise duration, time to onset of angina and time to 1mm ST-segment depression. Additionally, R compared to control significantly reduced weekly angina frequency and weekly nitroglycerin consumption. Finally, R compared to control did not significantly reduce supine systolic and diastolic blood pressure as well as heart rate, standing heart rate and diastolic blood pressure, whereas it modestly reduced standing systolic blood pressure. At sensitivity analysis, results were not influenced by concomitant background therapy. CONCLUSIONS In symptomatic patients with chronic CAD, R, added to conventional therapy, effectively reduces angina frequency and sublingual nitroglycerin consumption while prolonging exercise duration as well as time to onset of ischemia and to onset of angina with no substantial effects on blood pressure and heart rate.

EFFECTS OF SLEEP APNEA ON CARDIAC SYMPATHETIC ACTIVITY IN PATIENTS WITH SEVERE SYSTOLIC HEART FAILURE: A 123MIBG SCINTIGRAPHIC STUDY

Sleep apnea (SA) has been reported to worsen prognosis in patients with heart failure, likely through enhanced sympathetic drive arising from nocturnal arousals. However, very few studies have evaluated the association between SA and cardiac sympathetic innervation in heart failure patients. We

Dalla ricerca di base alla pratica clinica: nuove prospettive terapeutiche nello scompenso cardiaco

Despite significant advances in pharmacological and clinical treatment, heart failure remains a leading cause of morbidity and mortality worldwide. G-protein coupled receptors are a wide superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Since heart failure is characterized by the overactivity of different neurohormones, such as catecholamines and angiotensin II, responsible for several detrimental effects on the cardiovascular system, over the last decade therapeutic strategies targeting beta-adrenergic and angiotensin receptors have been developed. Despite the introduction of successful drug classes, such as beta-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors and sartans, heart failure still poses an enormous challenge, thus indicating the urgent need to develop innovative treatments that might counteract mechanisms involved in heart failure onset and progression. It is now established that a single receptor, activated by the same agonist, can elicit several different signaling pathways often resulting in opposite cellular responses, some beneficial and some detrimental. However, drugs currently used in heart failure target receptors on their extracellular domain by competing with the endogenous agonists. Thus, they can inhibit non-specifically all the receptor-related signaling pathways including those with beneficial activity whose blockade would not be desirable in heart failure. These observations stress the need for the generation of new therapeutic molecules able to target specific signaling pathways which might result in innovative therapies for cardiovascular disease.

Dalla ricerca di base alla pratica clinica

Despite significant advances in pharmacological and clinical treatment, heart failure remains a leading cause of morbidity and mortality worldwide. G-protein coupled receptors are a wide superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Since heart failure is characterized by the overactivity of different neurohormones, such as catecholamines and angiotensin II, responsible for several detrimental effects on the cardiovascular system, over the last decade therapeutic strategies targeting beta-adrenergic and angiotensin receptors have been developed. Despite the introduction of successful drug classes, such as beta-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors and sartans, heart failure still poses an enormous challenge, thus indicating the urgent need to develop innovative treatments that might counteract mechanisms involved in heart failure onset and progression. It is now established that a single receptor, activated by the same agonist, can elicit several different signaling pathways often resulting in opposite cellular responses, some beneficial and some detrimental. However, drugs currently used in heart failure target receptors on their extracellular domain by competing with the endogenous agonists. Thus, they can inhibit non-specifically all the receptor-related signaling pathways including those with beneficial activity whose blockade would not be desirable in heart failure. These observations stress the need for the generation of new therapeutic molecules able to target specific signaling pathways which might result in innovative therapies for cardiovascular disease.