Eccentric Dosing of Nitrates Does Not Increase Cardiac Events in Patients with Healed Myocardial Infarction

Kanamasa, Ken; Naito, Norikatsu; Morii, H.; Nakano, Kayoko; Tanaka, Yasushi; Kitayama, Kenji; Haku, R.; Kai, Tatsuya; Yonekawa, Osamu; Nagatani, Yusuke; Ishikawa, Kinji

doi:10.1291/hypres.27.563

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…Thus, the functional status of the ALDH-2 might be important not only for the metabolism and bioactivation of organic nitrates, but also for tissue recovery in the setting of ischemia. This evidence should be seen in light of preliminary studies reporting an increased incidence of cardiovascular events in patients undergoing nitrate therapy [36], and emphasizes the need of a prospective, randomized trial on the clinical long-term impact of these drugs. Importantly, preconditioning might have clinical implications [37], but our data emphasize the complexity of this phenomenon and support the concept that the protection observed in response to a single exposure to a preconditioning stimulus should not be assumed to imply that the same degree of protection would be observed in the chronic setting.…”

Section: Discussionmentioning

confidence: 99%

Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates

Lisi

Oelze²,

Dragoni

et al. 2012

Clin Res Cardiol

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We previously showed that upon repeated administration, the preconditioning-like effects of GTN are attenuated. The present data demonstrate a gradient in the extent of protection afforded by the two nitrates, suggesting that PETN-induced preconditioning is maintained after prolonged administration in a human in vivo model of endothelial dysfunction induced by ischemia. Using isolated human endothelial cells, we propose a mechanistic explanation for this observation based on differential effects of GTN versus PETN on the activity of mitochondrial aldehyde dehydrogenase.

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Section: Discussionmentioning

confidence: 99%

Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates

Lisi

Oelze²,

Dragoni

et al. 2012

Clin Res Cardiol

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“…However, we have also more recently understood that an excess accumulation of oxygen free radicals over time may mediate deleterious clinical effects of the chronic administration of these drugs [17]. Indeed, a recent meta-analysis has shown that long-term treatment with isosorbide mono-and dinitrate in postinfarction patients may be associated with a worse prognosis [11], and two randomized trials considering a treatment period >12 months have demonstrated that both the chronic and the intermittent administration of nitrates in the long term may increase the incidence of cardiac events [77,78]. Furthermore, chronic exposure to nitroglycerin induces a cardiac autonomic dysfunction, with a prevalence of the sympathetic nervous system activity over the vagal activity, which is related to an increased incidence of arrhythmias and a worsening of prognosis in patients with coronary heart disease and/or heart failure [79,80].…”

Section: A Summary Of Most Recent Acquisitions and Conclusionmentioning

confidence: 99%

Nitrates and Other Nitric Oxide Donors in Cardiology - Current Positioning and Perspectives

Bellisarii

Radico

Muscente

et al. 2011

Cardiovasc Drugs Ther

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Nitric oxide donors have been commonly used in the therapy of cardiovascular disease for more than 150 years. In spite of this longevity and the popularity of their use, it appears somewhat paradoxical that there is no current consistent use among cardiologists, as to both their indications and their optimal mode of administration. In part this results from their contradictory pharmacodynamics: when given acutely, their effectiveness is undisputable; however, their long-term efficacy is potentially limited by the development of tolerance and the induction of endothelial dysfunction, which may have negative prognostic implications. This review reports recent biochemical and pathophysiological acquisitions, re-examines the role of nitrates and other nitric oxide donors in cardiovascular medicine, comparing and commenting on international guidelines; and highlights areas of uncertainty, where more clinical research with these drugs would still be warranted.

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“…Since continuous dosing of nitrates facilitates the maintenance of a constant high blood concentration, this procedure is routinely used to treat unstable angina or heart failure; however, it is known that nitrate tolerance appears within 24 h with respect to improvement in pulmonary wedge pressure or exercise tolerance (3,5). As a strategy to overcome such tolerance, eccentric dosing has been recommended (9,14). Concerning the coronary vessel area, there was no significant difference in the pretreatment values between the continuous dosing group and the eccentric dosing group; however, in the eccentric dosing group and the untreated group, the coronary vessel area was significantly dilated compared to that in the continuous dosing group, suggesting that tolerance appeared in the continuous dosing group.…”

Section: Tolerance To Nitratesmentioning

confidence: 99%

Inhibition of Nitrate Tolerance without Reducing Vascular Response during Eccentric Dosing of Nitrates

et al. 2006

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It has been reported that the nitrate tolerance related to continuous dosing of nitrates reduces drug efficacy, and therefore eccentric dosing of nitrates is recommended. In this study, we investigated the appearance of nitrate tolerance related to continuous dosing of nitrates and prevention of nitrate tolerance during eccentric dosing by comparing the grade of coronary dilatation after sublingual nitroglycerin. Of 26 patients with ischemic heart disease who underwent elective cardiac catheterization, 8 patients were continuously administered nitrates, 8 patients were eccentrically administered nitrates, and 10 patients were not treated. We compared the coronary response to sublingual nitroglycerin among the 3 groups. In a coronary vessel without significant stenosis, the coronary vessel area, coronary lumen area, and mean coronary blood flow velocity after sublingual nitroglycerin were measured using intravascular ultrasound (IVUS). In the continuous dosing group, the maximal rate of change in the vessel area after sublingual nitroglycerin was 105 ± 1

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Eccentric Dosing of Nitrates Does Not Increase Cardiac Events in Patients with Healed Myocardial Infarction

Cited by 5 publications

References 58 publications

Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates

Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates

Nitrates and Other Nitric Oxide Donors in Cardiology - Current Positioning and Perspectives

Inhibition of Nitrate Tolerance without Reducing Vascular Response during Eccentric Dosing of Nitrates

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