A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris

Maltz, M. B.

doi:10.1016/0002-9149(89)90207-5

Cited by 44 publications

(15 citation statements)

References 19 publications

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“…Additionally, as a consequence of its capacity to open ATP-sensitive potassium channels, nicorandil exerts some metabolic effects and a form of preconditioning on the myocardium 41 . The antianginal action has been assessed in small and dated randomized trials with mixed results [41][42][43] .…”

Section: Key Points For Calcium-channel Blockersmentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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Chronic stable angina pectoris is the most prevalent symptomatic manifestation of ischaemic heart disease, and its management is a priority (BOX 1). Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revasculariza tion [1][2][3][4] . However, revascularization by either percutaneous coronary angioplasty or CABG surgery is indicated in patients who have significant artery steno sis (50% left main narrowing or proximal three-vessel disease) to reduce myocardial ischaemia and its adverse clinical manifestation. Antianginal agents are approved by documenting that they improve total exercise duration, together with a reduction in daily frequency of chronic stable angina compared with placebo and/or equivalence to an active comparator. Cardiovascular outcomes, although highly advocated, are not a pre requisite for regulatory approval. None of the antianginal drugs has been proved to reduce cardiovascular mortality or the rate of myocardial infarction. When patients are optimally treated, mortality for chronic stable angina is low, which might explain why all trials designed to improve prognosis have been negative. Guidelines recom mend a first-choice and a second-choice approach, based more on tradition and expert opinion, rather than evidence. This categorical approach has been questioned in the past couple of years 5-8 . Newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than is available for the traditional first-choice drugs. Equally, the often-needed combin ation of double or triple therapy is based on expert opinion and not related to the underlying pathophysio logy. What constitutes optimal antianginal treatment, therefore, varies considerably between countries, and the majority of doctors treat their patients according to their own preconceptions.A group of experts with experience and interest in chronic stable angina met at the University of Ferrara, Italy, to discuss an individualized approach to medical treatment of chronic stable angina, on the basis E X P E RT C O N S E N S U S D O C U M E N TA 'diamond' approach to personalized treatment of angina Abstract | In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for tr...

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Section: Key Points For Calcium-channel Blockersmentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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“…As a consequence of its capacity to open the ATP-sensitive potassium channels, it also exerts a sort of preconditioning on the myocardium [102]. In a large, multicentric, controlled, outcome study (IONA; the impact of nicorandil in angina) nicorandil reduced the composite of CV death, non-fatal myocardial infarction, or unplanned hospital admission for cardiac pain at a median of 1.6 years compared with placebo, despite 39% of patients withdrawing in the treated group because of headache [103].…”

Section: Drugs That Induce Vascular Smooth Muscle Relaxationmentioning

confidence: 99%

Treatment of Angina: Where Are We?

Balla

Pavasini

Ferrari³

2018

Cardiology

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Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the “classical” obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.

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“…Treadmill exercise.duration showed persistent increases, indicating the prolonged beneficial effects of nicorandil. Recently Camm and Maltz [121] reported that significant improvement in exercise capacity with the effect of placebo was maintained at 6 hours after single oral doses of 20, 40, and 60 mg of nicorandil and of placebo. Meany et al [122] administered twice-daily doses of nicorandil for 2 weeks, increasing from 5 mg to 20 mg, in chronic stable angina pectoris and showed a statistically significant improvement in exercise duration.…”

Section: Studies In Angina Pectarismentioning

confidence: 99%

“…Generally, nicorandil is administered at a dose of 5 to 10 mg given three times after meals or four times daily after meals and at bedtime. Administration four times daily may be more effective than less frequent dosing, particularly in cases of nocturnal or early morning angina, but more than one study in patients with stable exertional angina has shown a prolonged improvement in exercise tolerance for up to 6 hours after a single oral administration of 20 mg of nicorandil [120][121][122], although the plasma level declined so rapidly that there was no correlation between the plasma level and the duration of the antianginal effect. Sublingual nitroglycerin may be coadministered with nicorandil as needed to stop acute anginal attacks.…”

Section: Dosage and Administrationmentioning

confidence: 99%

Pharmacology and therapeutic effects of nicorandil

Kinoshita

Sakai²

1990

Cardiovasc Drug Ther

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Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.

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A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris

Cited by 44 publications

References 19 publications

A 'diamond' approach to personalized treatment of angina

A 'diamond' approach to personalized treatment of angina

Treatment of Angina: Where Are We?

Pharmacology and therapeutic effects of nicorandil

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