Continuous long‐term dosing with oral slow‐release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction

Kanamasa, Ken; Hayashi, Tetsuo; Takenaka, Toshihiko; Kimura, Akio; Ikeda, Akiko; Ishikawa, Kinji

doi:10.1002/clc.4960240908

Cited by 2 publications

(1 citation statement)

References 36 publications

(6 reference statements)

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“…Long-term post-MI treatment with nitrates reportedly could increase cardiac events, including nonfatal and fatal recurrent MI, death from CHF, and sudden death. [62][63][64][65] In these studies there were no measurements of platelet function made, so one cannot determine whether the presence or absence of an antiplatelet effect had any impact.…”

Section: Is the Antiplatelet Effect Of Nitrates/nitrovasodilators Of mentioning

confidence: 97%

The Antiplatelet Effects of Nitrates

Zhou¹,

Frishman²

2010

Cardiology in Review

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Organic nitrates have been used for over a century in cardiovascular therapy and are still widely used in the treatment of acute coronary syndromes, chronic angina pectoris, and congestive heart failure. Nitrates, together with sodium nitroprusside, generally referred to as nitrovasodilators, exert their biologic effects via the release of nitric oxide. They are also known as nitric oxide donors. The mechanism of action of these drugs is traditionally believed to lie in their arterial vasodilation and venodilation effects, resulting in an improvement of coronary artery blood supply and/or reduction of cardiac workload in the treatment of coronary artery disease and congestive heart failure. Recently it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which would add further rationale for the use of these drugs in atherothrombotic diseases. Research has shown that nitrovasodilators can nonselectively inhibit platelet aggregation induced by multiple stimuli. However, clinical trials have yielded conflicting results regarding clinical outcome, especially with long-term nitrate use. The potentially beneficial effects of nitrates could be negated by the development of tolerance and the generation of deleterious oxidative stress causing endothelial dysfunction during continuous nitrate administration. Much progress has been made in the development of new nitric oxide donors devoid of oxidant-generating properties. Novel combination therapies with nitrovasodilators plus antioxidants or agents with antioxidant properties have shown promise in reducing or reversing tolerance, potentiating antiplatelet effects, and improving clinical outcome. It is expected that clinical introduction of novel nitrovasodilator regimens will provide a new approach to the prevention and treatment of atherothrombotic diseases. Large-scale clinical trials will ultimately provide the evidence-based answers.

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Section: Is the Antiplatelet Effect Of Nitrates/nitrovasodilators Of mentioning

confidence: 97%

The Antiplatelet Effects of Nitrates

Zhou¹,

Frishman²

2010

Cardiology in Review

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Lack of Bioequivalence between Different Formulations of Isosorbide??Dinitrate and Hydralazine and??the??Fixed-Dose Combination of??Isosorbide Dinitrate/Hydralazine

Tam¹,

Sabolinski²,

Worcel³

et al. 2007

Clinical Pharmacokinetics

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The blood concentrations of hydralazine obtained with the tablet formulation tested in V-HeFT II were markedly lower than those obtained with the capsule formulation tested in V-HeFT I or the FDC ISDN/HYD single tablet used in A-HeFT. The apparently modest effect on survival observed in V-HeFT II could be explained in part by the poor hydralazine bioavailability of the tablet preparation used in this trial. ISDN exposures were similar in the two trials. The ISDN-hydralazine formulation used in V-HeFT II was not bioequivalent to the formulation used in V-HeFT I or to the FDC ISDN/HYD that had demonstrated a significant survival benefit in A-HeFT.

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Continuous long‐term dosing with oral slow‐release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction

Cited by 2 publications

References 36 publications

The Antiplatelet Effects of Nitrates

The Antiplatelet Effects of Nitrates

Lack of Bioequivalence between Different Formulations of Isosorbide??Dinitrate and Hydralazine and??the??Fixed-Dose Combination of??Isosorbide Dinitrate/Hydralazine

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