Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial

Boden, William E.; Gilst, Wiek H. van; Scheldewaert, Rudy; Starkey, Ian R.; Carlier, Marc; Julian, Desmond G.; Whitehead, Anne; Bertrand, Michel E.; Col, Jacques; Pedersen, Ole Lederballe; Lie, Kong I.; Santoni, J. P.; Fox, Kim

doi:10.1016/s0140-6736(00)02262-5

Cited by 81 publications

(16 citation statements)

References 32 publications

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“…The use of calcium channel blockers in the presence of LVD has been challenged in clinical practice in the past decade [25]. However, among the calcium antagonists, diltiazem was demonstrated to exhibit the best profile without a significant negative inotropic effect and an improvement in cardiac function following coronary ischaemia [26].…”

Section: Discussionmentioning

confidence: 99%

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

Peták

Albu

Lele

et al. 2012

Respiratory Research

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BackgroundThe effectiveness of strategies for treatment of the altered static lung volume and against the development of bronchial hyperreactivity (BHR) following a left ventricular dysfunction (LVD) induced by myocardial ischaemia was investigated in a rat model of sustained postcapillary pulmonary hypertension.MethodsAirway resistance (Raw) was identified from the respiratory system input impedance (Zrs) in four groups of rats. End-expiratory lung volume (EELV) was determined plethysmographically, and Zrs was measured under baseline conditions and following iv infusions of 2, 6 or 18 μg/kg/min methacholine. Sham surgery was performed in the rats in Group C, while the left interventricular coronary artery was ligated and Zrs and its changes following identical methacholine challenges were reassessed in the same rats 8 weeks later, during which no treatment was applied (Group I), or the animals were treated daily with a combination of an angiotensin enzyme converter inhibitor and a diuretic (enalapril and furosemide, Group IE), or a calcium channel blocker (diltiazem, Group ID). The equivalent dose of methacholine causing a 100% increase in Raw (ED50) was determined in each group. Diastolic pulmonary arterial pressure (PapD) was assessed by introducing a catheter into the pulmonary artery.ResultsThe sustained presence of a LVD increased PapD in all groups of rats, with variable but significant elevations in Groups I (p = 0.004), ID (p = 0.013) and IE (p = 0.006). A LVD for 8 weeks induced no changes in baseline Raw but elevated the EELV independently of the treatments. In Group I, BHR consistently developed following the LVD, with a significant decrease in ED50 from 10.0 ± 2.5 to 6.9 ± 2.5 μg/kg/min (p = 0.006). The BHR was completely abolished in both Groups ID and IE, with no changes in ED50 (9.5 ± 3.6 vs. 10.7 ± 4.7, p = 0.33 and 10.6 ± 2.1 vs. 9.8 ± 3.5 μg/kg/min p = 0.56, respectively).ConclusionsThese findings suggest that a LVD following coronary ischaemia consistently induces BHR. The more consistent efficacy of both treatment strategies in preventing BHR than in treating the adverse pulmonary vascular consequences suggests the benefit of both calcium channel blockade and ACE inhibition to counteract the airway susceptibility following a LVD.

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Section: Discussionmentioning

confidence: 99%

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

Peták

Albu

Lele

et al. 2012

Respiratory Research

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“…Similarly, the earliest detection of a lack of efficacy of the experimental treatment in the EMIAT trial was provided by the triangular test. While several trials have been stopped early for harm from experimental therapy [5, 18], early stopping for lack of difference between the experimental and the control treatments remain s rare [12]. In contrast with the triangular test, the Lan & DeMets method does not provide rules to stop a trial early when there is a lack of difference between treatments.…”

Section: Discussionmentioning

confidence: 99%

Planning and monitoring of placebo‐controlled survival trials: comparison of the triangular test with usual interim analyses methods

Hulot

Cucherat²,

Charlesworth³

et al. 2003

Brit J Clinical Pharma

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Aims For ethical and economic reasons, interim analysis of phase III clinical trials is essential. This study was conducted to compare the efficiency of two interim analysis procedures, which could be used to allow early termination of a clinical trial. Methods We made a post hoc application of two interim analysis methods (Lan & DeMets with O’Brien–Flemming modification, and the triangular test according to Whitehead) by using individual patient data from four published placebo‐controlled survival trials. We determined the date the trial would have been stopped had each method been used, and we estimated consequent results in terms of events and patient numbers included in the trial, the duration of the trial, and on treatment effect. Results The triangular test provided the lowest number of events required to reach a conclusion of the trials while providing an accurate estimate of experimental treatment effects. The triangular test thus indicated the smallest number of patients that would have been enrolled, and the shortest trial duration. The difference between the methods was most important with a detrimental effect of experimental treatment: the number of required events was reduced by 75% and the trial duration was shortened by 48% with the triangular test compared to the Lan & DeMets method. Conclusions Stopping a trial early must depend on the clinical context. It is most important to stop a placebo‐controlled trial as soon as possible when the experimental treatment can be shown deleterious. In such a situation the triangular test is more appropriate than the Lan & DeMets method. When a treatment effect is no different from, or better than, placebo the triangular test is also superior but the importance of premature termination of the trial in such cases has to be balanced against the inevitable reduction of information that the trial can provide.

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“…85 However, a moderate-sized randomized trial of diltiazem vs placebo after thrombolysis found no significant advantage to active therapy even when the combined primary end point included refractory ischemia. 86 Thus, the reported differences by CCB class (non-DHP vs DHP) are without prospective confirmatory evidence of non-DHP benefits for major cardiovascular outcomes.…”

Section: Coronary Artery Disease-acute Coronary Syndromesmentioning

confidence: 98%

Epidemiologic Review of the Calcium Channel Blocker Drugs

Kizer¹,

Kimmel²

2001

Arch Intern Med

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In the setting of soaring popularity, postmarketing studies of calcium channel blockers came to suggest an increase in a variety of major adverse end points. The evidence, however, was largely observational, and large-scale trials capable of addressing the concerns were wanting. Clinical trials now support the safety and efficacy of the long-acting dihydropyridines for patients with both uncomplicated and diabetic hypertension, although conventional therapies and, in the latter case, angiotensin-converting enzyme inhibitors have superior proof of benefit. By contrast, short-acting dihydropyridines should be avoided. In the acute coronary syndromes, beta-blockers remain the treatment of choice; the evidence for nondihydropyridines remains inconclusive. Stable angina calls for beta-blockers as first-line therapy and nondihydropyridines as second-line therapy, whereas in ventricular dysfunction, safety data for nondihydropyridines are lacking. Initial reports of cancer, bleeding, and suicide have been contradicted by subsequent data, making the associations uncertain or unlikely. Remaining questions await completion of ongoing trials to better define the indications for these agents.

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Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial

Cited by 81 publications

References 32 publications

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

Prevention of airway hyperresponsiveness induced by left ventricular dysfunction in rats

Planning and monitoring of placebo‐controlled survival trials: comparison of the triangular test with usual interim analyses methods

Epidemiologic Review of the Calcium Channel Blocker Drugs

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