Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial

Poole‐Wilson, Philip A.; Lubsen, Jacobus; Kirwan, Bridget‐Anne; Dalen, Fred J. van; Wagener, Gilbert; Danchin, Nicolás; Just, H.; Fox, Keith A.A.; Pocock, Stuart J.; Clayton, Tim; Motro, Michael; Parker, John D.; Bourassa, Martial G.; Dart, Anthony M.; Hildebrandt, Per; Hjalmarson, Åke; Kragten, Johannes A.; Molhoek, G. P.; Otterstad, Jan-Erik; Seabra-Gomes, R; Soler‐Soler, Jordi; Weber, Simon

doi:10.1016/s0140-6736(04)16980-8

Cited by 468 publications

(297 citation statements)

References 19 publications

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“…• Calcium-channel blockers do not improve survival of patients with chronic stable angina with or without myocardial infarction or left ventricular dysfunction and, when used in patients with heart failure, they might have deleterious effects on outcome 37,38 .…”

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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“…The CCB nifedipine was recently reported to upregulate endothelial superoxide dismutase expression by stimulating vascular endothelial growth factor (VEGF) production from adjacent vascular smooth muscle cells and reducing oxidative stress (8,9). In the recent clinical trial, nifedipine reduced the new onset of overt heart failure and the need for coronary angioplasty in patients with stable angina (10).…”

Section: Introductionmentioning

confidence: 99%

Nifedipine Enhances the Cardioprotective Effect of an Angiotensin-II Receptor Blocker in an Experimental Animal Model of Heart Failure

et al. 2005

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This study was designed to examine the hypothesis that a calcium channel blocker nifedipine (CCB) could enhance the cardioprotective effect of an angiotensin-II receptor blocker candesartan (ARB) in the treatment for heart failure. Isoproterenol (ISP) was injected into male rats at 300 mg/kg to produce progressive heart failure. Three months later, the rats were divided into 4 groups and treated for 4 weeks with 1) vehicle (n =20), 2) ARB at 0.2 mg/kg/day (n =6), 3) CCB at 10 mg/kg/day (n =6), or 4) both drugs (n =8). Rats injected with saline served as controls (n =13). ISP caused severe myocardial degeneration and decreased the capillary density (D cap) of the left ventricular (LV) myocardium (mean ± SD: 2,197 ± 627 vs. 2,847 ± 298 N/mm 2 for normal controls), while increasing plasma thiobarbituric acid-reactive substances (TBARS; 3.6 ± 1.1 vs. 1.9±0.5 nmol/ml

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“…Nifedipine GITS did have a positive effect on two out of three prespecified secondary combined end points: the combined rate of death, major CV events, revascularisation and coronary angiography was reduced by 11%, although this was due almost entirely to fewer coronary angiograms; and any vascular event was reduced by 9%, due mainly to fewer coronary angioplasties and revascularisation procedures. 18 On the other hand, the recent FEVER study, also using a dihydropyridine CCB, did show a major reduction in cardiac events in association with a small difference in BP with felodipine. 24 The level of CV risk among patients in the ACTION trial was very similar to that in EUROPA (mortality rate in the placebo group was 1.53 per 100 patient-years of follow-up), and the difference in BP between active and placebo groups was also similar in the two trials: 6/3 mmHg (ACTION) vs. 5/2 mmHg (EUROPA).…”

Section: O P Y R I G H T J R a A S L I M I T E D R E P R O D U C T mentioning

confidence: 93%

Review: Angiotensin-converting enzyme inhibitors and coronary heart disease prevention

Donnelly

Manning

2007

J Renin Angiotensin Aldosterone Syst

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A number of large randomised controlled trials have shown that angiotensin-converting enzyme (ACE) inhibitors, compared with placebo or other blood pressure-lowering drugs, improve coronary heart disease outcomes (fatal and nonfatal myocardial infarction, and coronary revascularisation) in diverse patient groups, e.g. in primary and secondary prevention, those with and without left ventricular dysfunction, and among hypertensive and non-hypertensive

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Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial

Cited by 468 publications

References 19 publications

A 'diamond' approach to personalized treatment of angina

A 'diamond' approach to personalized treatment of angina

Nifedipine Enhances the Cardioprotective Effect of an Angiotensin-II Receptor Blocker in an Experimental Animal Model of Heart Failure

Review: Angiotensin-converting enzyme inhibitors and coronary heart disease prevention

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