Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 ± 5 to 107 ± 3 mm Hg: mean ± SEM; P < 0.002) and diastolic blood pressure (from 85 ± 3 to 75 ± 2 mm Hg; P < 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 ± 2 to 27 ± 2 mm Hg (P < 0.005). The left ventricular filling pressure decreased from 24 ± 1 to 19 ± 1 mm Hg (P < 0.0001). A significant increase in cardiac index (from 2.33 ± 0.13 to 2.69 ± 0.15 l/min per m²; P < 0.001) and in stroke volume index (from 24 ± 2 to 28 ± 2 ml/beats per m²; P < 0.005) was registered. Systemic vascular resistance fell from 1742 ± 145 to 1308 ± 85 dynes/sec per cm⁻⁵ (P < 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 ± 1.6 to 5.1 ± 1.2 mm Hg; P < 0.0001), in mean pulmonary arterial pressure (from 32 ± 1 to 23 ± 1 mm Hg; P < 0.00001) and in left ventricular filling pressure (from 23 ± 1 to 16 ± 1 mm Hg; P < 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.     

The efficacy and safety of high-dose verapamil and diltiazem in the long-term treatment of stable exertional angina

The efficacy and safety of high-dose verapamil (480 mg/day) and diltiazem therapy (360 mg/day) were compared in separate cohorts of 26 and 20 patients, respectively. All patients had stable exertional angina and underwent an initial 6-week double-blind, placebo-controlled, randomized phase followed by a 12-month open-label period. Angina attacks were reduced by verapamil (6.3 +/- 7.5 to 2.5 +/- 4.1 attacks per week, p less than 0.001) and by diltiazem (9.2 +/- 7.5 to 3.0 +/- 3.1 attacks per week, p less than 0.001), while treadmill time increased with both verapamil (372 +/- 132 to 444 +/- 108 s, p less than 0.001) and diltiazem (412 +/- 175 to 536 +/- 164 s, p less than 0.001) during the short-term study. Both agents continued to show similar salutory effects at the end of one year. The beneficial effects of both drugs appeared to be related in part to a reduction of the rate-pressure product during submaximal exercise (12% by verapamil, 7% by diltiazem, both p less than 0.05). Adverse effects were few and consisted primarily of mild constipation in six patients taking verapamil, and pedal edema and transient flushing in 2 patients each using diltiazem. Thus, high-dose verapamil and diltiazem have similar beneficial effects and are safe for the long-term treatment of effort-related angina pectoris.     

Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial

OBJECTIVE: To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout. METHODS: A randomized, double-blind, active-comparator study was conducted at 42 sites. A total of 189 men and women (> or =18 years of age) who were experiencing an acute attack (< or =48 hours) of clinically diagnosed gout were treated for 8 days with etoricoxib, 120 mg/day (n = 103), or indomethacin, 50 mg 3 times a day (n = 86). The primary efficacy end point was the patient's assessment of pain in the study joint (0-4-point Likert scale) over days 2-5. Safety was assessed by adverse experiences (AEs) occurring during the trial. RESULTS: Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient's assessment of pain in the study joint. The difference in the mean change from baseline over days 2-5 was -0.08 (95% confidence interval -0.29, 0.13) (P = 0.46), which fell within the prespecified comparability bounds of -0.5 to 0.5. Secondary end points over the 8-day study, including the onset of efficacy, reduction in signs of inflammation, and patient's and investigator's global assessments of response to therapy, confirmed the comparable efficacy of the two treatments. The etoricoxib-treated patients had a numerically lower incidence of AEs (43.7%) than did the indomethacin-treated patients (57.0%) and a significantly lower incidence of drug-related AEs (16.5% versus 37.2%; P < 0.05). CONCLUSION: Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout. Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily, and it was generally safe and well tolerated.     

The significance of myocardial ischaemia and verapamil treatment on the prevalence of supraventricular tachyarrhythmias in patients recovering from acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.

Twenty-four hour Holter monitoring and symptom-limited exercise testing were carried out prior to discharge in 157 patients recovering from acute myocardial infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were recorded in 15%, and ST segment depression during exercise in 27%. No association between exercise-provoked ischaemia and SVT was found in the late hospital phase of myocardial infarction. After the tests, patients were double-blindly randomized to treatment with verapamil 120 mg t.i.d. or placebo. One month after randomization 24 h Holter monitoring was repeated in 125 patients (verapamil = 63, placebo = 62). At one month a significantly increased incidence of SVT was found in the placebo group (25%) compared to the verapamil-treated patients (9%) (P = 0.04). The increased prevalence in the placebo group was mainly due to an increased incidence of SVT in patients with exercise-induced ischaemia (P = 0.03). This increment was blurred in the verapamil group. In conclusion, the prevalence of SVT increases during the first month after myocardial infarction. The increase is most pronounced in patients with residual myocardial ischaemia and seemed to be prevented by treatment with verapamil.     

Comparative effects of prolonged therapy with four calcium ion antagonists (diltiazem,nicardipine, tiapamil and verapamil) in patients with chronic stable angina pectoris

Summary The comparative effects of prolonged chronic therapy with diltiazem, nicardipine, tiapamil and verapamil on exercise tolerance, ST-segment changes and heart rate were examined in 63 patients with established chronic stable angina pectoris. Multistage computer-assisted symptom-limited tread-mill exercise tests were performed after 2 weeks of placebo (baseline) and then after 4 months of open-label chronic drug therapy. Diltiazem improved the exercise duration by 95% (p<0.001), nicardipine by 45% (p<0.001), tiapamil by 69% and verapamil by 79% (p<0.001). Maximal ST-segment depression was not altered by any of the drugs, but time to the development of 1 mm ST-segment depression was significantly improved in all cases. Diltiazem and verapamil reduced the heart rate at rest significantly by 6 and 8 beats/minute, respectively, whereas nicardipine increased it by 10 beats/minute (p<0.02), and tiapamil did not produce any significant change. Maximal heart rate at the peak of exercise was increased by 14% with nicardipine (p<0.001) and 6% with verapamil (p<0.05), whereas diltiazem and tiapamil did not produce any appreciable effect. The rate-pressure product at the peak of exercise remained unaltered with diltiazem, tiapamil and verapamil, but with nicardipine it increased significantly to 222±10 units from a baseline of 175±6 units with placebo. During diltiazem treatment, 1 patient died of myocardial infarction after 8 weeks of therapy. During tiapamil, 2 patients were withdrawn after 10 weeks because they developed unstable angina. During verapamil therapy, 4 patients were withdrawn; 1 developed myocardial infarction after 4 weeks, 2 patients developed worsening angina and 1 patient showed prolongation of the PR interval after 8 weeks of treatment. Constipation was reported by 7 patients during verapamil therapy. During nicardipine treatment one patient reported pedaloedema and dyspnoea after 16 weeks and was withdrawn. At the dosages used, all 4 calcium ion antagonists studied have been shown to be effective antianginal agents during long-term therapy, but differing effects on heart rate and rate-pressure product suggest that they do not have a similar mechanism of action.     

Interrelationship between coagulant activity and tissue-type plasminogen activator (t-PA) system in acute ischaemic heart disease. Possible role of the endothelium.

Patients with unstable angina pectoris (UAP; n = 20) and acute myocardial infarction (AMI; n = 34) were studied in the acute phase of ischaemic heart disease. We found significantly higher levels of thrombin-antithrombin-III (TAT) complexes, lower levels of systemic tissue plasminogen activator (t-PA) activity, and higher levels of plasminogen activator inhibitor (PAI) activity in the AMI patients compared to the UAP patients. In contrast to these specific changes, general acute phase reactants such as C-reactive protein, fibrinogen and von Willebrand factor did not differ significantly between the two groups. Studies of the relationship between coagulation (TAT-complexes) and fibrinolysis data revealed a significant positive correlation between plasma antigen concentrations of TAT-complexes and t-PA (P less than 0.02), and between TAT-complexes and PAI-I (P less than 0.002). These observations indicate a common pathophysiological mechanism underlying the changes in coagulation and fibrinolysis, suggesting that coagulation activity and t-PA-related fibrinolysis are interrelated processes in vivo, and probably take place at the level of the endothelial cell.     

替罗非班强化抗栓治疗高龄非ST段抬高型急性冠脉综合征的有效性及安全性评价

目的 评价强化抗栓治疗（阿司匹林、氯吡格雷联合替罗非班）高龄（≥75岁）非ST段抬高急性冠脉综合征（NSTEACS）患者的有效性和安全性.方法 入选高龄非ST段抬高型急性冠脉综合征患者126例,随机分为观察组（60例）和对照组（66例）.对照组给予阿司匹林、低分子肝素、氯吡格雷等常规治疗;观察组在常规治疗基础上加用替罗非班（静脉负荷量0.4 μg·kg1·min-1,30 min后以0.1 μg ·kg-1·min-1维持,持续48～72 h）.观察两组患者30 d主要不良心血管事件（MACE）、7d心绞痛控制率及出血等不良反应的发生情况.结果 观察组30 d的MACE发生率为5.00％,对照组为13.64％,两组患者30 d MACE发生率差异有统计学意义（P＜0.05）.观察组与对照组7d心绞痛控制率分别为93.33％和77.27％,差异有统计学意义（P＜0.05）.观察组与对照组出血发生率分别为10.00％和7.58％,差异无统计学意义（P＞0.05）.两组均无严重的出血并发症,观察组发生1例血小板减少,但与对照组比较无统计学意义.结论 替罗非班强化抗栓治疗高龄非ST段抬高急性冠脉综合征患者,能有效缓解心绞痛症状,降低30 d的MACE发生率,不增加出血风险.     

全反式维甲酸联合三氧化二砷治疗初发急性早幼粒细胞白血病的疗效观察

目的观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗急性早幼粒细胞白血病(APL)的完全缓解(CR)率和不良反应。方法ATRA25mg.m-2.d-1,As2O3(0.1%溶液)10mL/d联合治疗初发APL直至CR。根据外周血白细胞计数、维甲酸综合征,以及肝功能变化调整ATRA和As2O3的剂量。结果29例初发APL患者,早期死亡2例,27例获得CR,CR率93.1%。获得CR的平均时间为(25.2±3.5)d。没有发现严重不良反应。结论ATRA联合As2O3治疗初发APL疗效好,不良反应患者能耐受。     

Calcium channel antagonists part II: Use and comparative properties of the three prototypical calcium antagonists in ischemic heart disease,including recommendations based on an analysis of 41 trials

Summary An analysis of 41 trials of angina of all varieties confirms that calcium antagonists are an important advance and are now established therapy for these syndromes. In effort angina, verapamil in a dose of 360–480 mg daily is better than propranolol in standard doses. Although nifedipine is highly effective against vasospastic angina, its use in threatened myocardial infarction is not supported by recent studies, unless combined with a beta-blocker. Diltiazem has recently been tested with apparent benefit in non-Q-wave myocardial infarction. Otherwise, these calcium antagonist agents will all seem to have approximate equipotency in clinical ischemic syndromes including effort and vasospastic angina. Subjective side effects seem most troublesome in the case of nifedipine. All three calcium antagonists, especially nifedipine, have been successfully combined with beta-blocker therapy, yet occasional additive negative inotropic or chronotropic or dromotropic interactions may occur when verapamil or diltiazem is added to beta-blockade, and occasionally the direct negative inotropic potential of nifedipine may may become evident. The choice between the calcium antagonists is determined not only by the clinical picture but also by the anticipated side effects in a given patient and by the overall cardiovascular status. In patients with supraventricular tachycardias or sinus tachycardia, verapamil or diltiazem is preferred, whereas in patients with a resting bradycardia or borderline heart failure nifedipine is likely to be chosen.[This article appeared in Cardiovascular Drugs & Therapy, 1: 461–491, 1988]     

Calcium channel antagonists part II: Use and comparative properties of the three prototypical calcium antagonists in ischemic heart disease,including recommendations based on an analysis of 41 trials

Summary An analysis of 41 trials of angina of all varieties confirms that calcium antagonists are an important advance and are now established therapy for these syndromes. In effort angina, verapamil in a dose of 360–480 mg daily is better than propranolol in standard doses. Although nifedipine is highly effective against vasospastic angina, its use in threatened myocardial infarction or severe unstable angina is not supported by recent studies, unless combined with a betablocker. Diltiazem has recently been tested with apparent benefit in non-Q-wave myocardial infarction. Otherwise, these calcium antagonist agents all seem to have approximate equipotency in clinical ischemic syndromes including effort and vasospastic angina. Subjective side effects seem most troublesome in the case of nifedipine. All three calcium antagonists, especially nifedipine, have been successfully combined with beta-blocker therapy, yet occasional additive negative inotropic or chronotropic or dromotropic interactions may occur when verapamil or diltiazem is added to beta-blockade, and occasionally the direct negative inotropic potential of nifedipine may become evident. The choice between the calcium antagonists is determined not only by the clinical picture but also by the anticipated side effects in a given patient and by the overall cardiovascular status. In patients with supraventricular tachycardias or sinus tachycardia, verapamil or diltiazem is preferred, whereas in patients with a resting bradycardia or borderline heart failure nifedipine is likely to be chosen.This report was refereed by four external reviewers whose opinions were transmitted to the San Francisco office of this journal for editorial decision.     

Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial

The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML patients aged <60 years. Patients who had reached a complete remission (CR) after two courses of induction chemotherapy and who were not eligible for a human leucocyte antigen-matched sibling SCT (n = 130), were randomized after a third consolidation cycle of chemotherapy between high-dose cytotoxic treatment and autologous bone marrow transplantation or no further treatment. No significant differences in disease-free survival and overall survival were observed between the two treatment arms. A slightly better overall survival in the no further treatment arm was because of fewer deaths in the first CR and a significantly better overall survival after the first relapse. The results are discussed in relation to the generic problems of applying autologous transplantation and in the perspective of the limited statistical power of this and other previously published studies.