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San Raffaele Cimena, Italy

Savarese G.,University of Naples Federico II | Rosano G.,Clinical and Experimental Research Center | D'Amore C.,University of Naples Federico II | Musella F.,University of Naples Federico II | And 10 more authors.
International Journal of Cardiology | Year: 2013

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 1 mm 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 1 mm 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. © 2013 Elsevier Ireland Ltd.


Savarese G.,University of Naples Federico II | Costanzo P.,University of Naples Federico II | Costanzo P.,University of Hull | Cleland J.G.F.,University of Hull | And 4 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives: The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. Background: ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. Methods: Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. Results: ACE-Is significantly reduced the risk of the composite outcome (odds ratio [OR]: 0.830 [95% confidence interval (CI): 0.744 to 0.927]; p = 0.001), MI (OR: 0.811 [95% CI: 0.748 to 0.879]; p < 0.001), stroke (OR: 0.796 [95% CI: 0.682 to 0.928]; p < 0.004), all-cause death (OR: 0.908 [95% CI: 0.845 to 0.975]; p = 0.008), new-onset HF (OR: 0.789 [95% CI: 0.686 to 0.908]; p = 0.001), and new-onset DM (OR: 0.851 [95% CI: 0.749 to 0.965]; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 [95% CI: 0.869 to 0.975], p = 0.005), stroke (OR: 0.900 [95% CI: 0.830 to 0.977], p = 0.011), and new-onset DM (OR: 0.855 [95% CI: 0.798 to 0.915]; p < 0.001). Conclusions: In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used. © 2013 American College of Cardiology Foundation.

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