Antianginal, hemodynamic and coronary vascular effects of captopril in stable angina pectoris

A pilot study was performed to assess the short-term effects of intravenous captopril on anginal threshold and systemic and coronary hemodynamics in patients with stable angina pectoris. Twelve patients with documented coronary artery disease, stable angina pectoris and normal left ventricular function were studied by an incremental atrial pacing stress test before and after intravenous captopril (n = 8) or placebo (n = 4). There were no significant differences in the extent of coronary disease or left ventricular function between the 2 groups and resting plasma-renin levels were normal. Captopril increased the time to angina (14 +/- 4 to 9 +/- 5 minutes, p less than 0.05), increased heart rate at development of angina (126 +/- 7 to 142 +/- 7 beats/min, p less than 0.05) and tended to increase coronary blood flow (229 +/- 154 to 296 +/- 259 ml/min, p = 0.11) and decrease coronary vascular resistance (53 +/- 10 to 47 +/- 3 dynes s cm-5/1,000, p = 0.11) at peak stress without alteration in systemic hemodynamics. No significant changes were seen after placebo administration. Therefore, intravenous captopril appears to cause a short-term increase of coronary vascular reserve, and anginal threshold in patients with chronic stable angina. This effect appears to be independent of inhibition of the systemic renin-angiotensin system or systemic hemodynamic changes.     

卡托普利治疗稳定劳力型心绞痛的临床效果

目的卡托普利在治疗稳定性劳力型心绞痛在临床治疗中的效果分析。方法选取2005年3月~2012年10月来我院进行治疗的稳定性劳力型心绞痛患者共200例,年龄为53~72岁,并随机分成两组观察组与对照组,每组各100例。对照组与观察组分别采用常规的治疗方法以及在常规治疗方法的基础上施以卡托普利治疗。其中,常规的治疗方法主要是采用β-受体阻滞剂,阿司匹林,硝酸酯类以及钙拮抗剂进行治疗。对两组的治疗情况进行观察与分析。结果在经过一段时间的临床应用治疗之后,观察组与对照组的稳定性劳力性心绞痛的治疗效果有着明显的改善,但是观察组的治疗效果明显优于对照组,观察组与对照组见的心率明显不一样,观察组慢于对照组。并且在运动过程中观察组的心绞痛病症诱发时间明显长于对照组。结论卡托普利在治疗稳定劳力型心绞痛病症的过程中有着显著的疗效,具有重要的临床意义。     

卡托普利治疗稳定劳力型心绞痛的临床效果

目的观察卡托普利在稳定劳力型心绞痛治疗中的作用。方法选择稳定劳力型心绞痛患者265例,将其随机分为常规治疗组（阿司匹林、β-受体阻滞剂、钙拮抗剂、硝酸酯类）129例,年龄（57±111）岁,卡托普利组（常规治疗基础上加卡托普利12.5 mg,3次/d）136例,年龄（58±10）岁。观察治疗24周时两组患者心绞痛分级,测量心率、血压,计算心率×收缩压值;并做运动心电图,观察运动中诱发心绞痛时间（s）、ST段下移≥0.1 mV时或心绞痛发作时的心率、ST段下移最大程度（mV）及ST段下移持续最长时间（s）。结果两组治疗24周后心绞痛分级均明显改善,卡托普利组较常规治疗组心率显著减慢,SBP、DBP及心率×收缩压值显著降低,运动中诱发心绞痛的时间延长,ST段下移≥0.1 mV或心绞痛发作时心率增加,ST段下移持续最长时间缩短。结论卡托普利治疗劳力型心绞痛患者能减轻心绞痛症状,增加运动耐量。     

The ability of captopril to enhance the anti-anginal effect of isosorbide dinitrate in patients with stable exercise-induced angina pectoris]

The interaction between isosorbide dinitrate (ISDN) and the angiotensin-converting enzyme inhibitor captopril was investigated in 14 patients with coronary heart disease concurrent with stable exercise-induced angina pectoris. The efficacy of placebo, ISDN, 10 mg, captopril, 50-100 mg, and ISDN + captopril was evaluated in each patient by pharmacodynamic treadmill studies. The single-blind, randomized technique was applied. Captopril alone produced a weak antianginal effect. The concomitant use of ISDN and captopril showed significantly more marked and prolonged effects than ISDN alone. The highest effect was exhibited by ISDN supplemented with captopril in 6 patients who had been refractory to ISDN alone. Thus, captopril may potentiate the antianginal effect of ISDN.     

Hemodynamic effects of intravenous prostacyclin in stable angina pectoris

Prostacyclin (PGI2) is a naturally occurring vasodilator and inhibitor of platelet aggregation that produces vasodilatation of the systemic, pulmonary and coronary vascular beds in animal models. Because the endogenous production of PGI2 is reduced in those with coronary arterial disease (CAD), it may have a therapeutic role in patients with ischemic heart disease. To assess its safety and efficacy in this clinical setting, 17 patients with stable angina and CAD received an incremental intravenous infusion of either PGI2 (n = 10) to a maximum dose of 10 ng/kg/min (average 9.8 +/- 0.8 [mean +/- standard deviation]), or diluent buffer solution (placebo) (n = 7). All patients who received PGI2 became flushed, but experienced no other adverse effects PGI2 caused an increase in heart rate (66 +/- 11 to 80 +/- 11 beats/min, p less than 0.001) and cardiac index (2.88 +/- 0.65 to 3.97 +/- 1.17 liters/min/m2, p less than 0.001) and a decrease in mean femoral arterial pressure (96 +/- 18 to 86 +/- 11 mm Hg, p less than 0.001), but no change in mean pulmonary arterial or capillary wedge pressure. Total systemic and pulmonary vascular resistance decreased significantly (p less than 0.001). In response to PGI2, mean coronary sinus blood flow did not change significantly (100 +/- 40 to 121 +/- 52 ml/min), but coronary vascular resistance decreased (1.07 +/- 0.40 to 0.83 +/- 0.36 U, p less than 0.001). No variable was altered by placebo infusion. PGI2 caused a marked increase in 6-keto PGF1 alpha (the stable metabolite of PGI2) concentrations in both arterial (42 +/- 29 to 567 +/- 216 pg/ml, p less than 0.001) and venous (46 +/- 31 to 604 +/- 229 pg/ml, p less than 0.001) blood but no demonstrable change in plasma renin activity. Thus, intravenous PGI2 to a dosage of 10 ng/kg/min is a safe and effective systemic, pulmonary and coronary arterial vasodilator in patients with CAD and stable angina pectoris.     

Enhancement of the efficacy of isosorbide dinitrate by captopril in stable angina pectoris.

This study was designed to assess whether the angiotensin-converting enzyme inhibitor captopril could potentiate the efficacy of a single dose of oral isosorbide dinitrate (ISDN) in patients with coronary artery disease. Fourteen men (mean age 53 years) with stable angina pectoris were studied. In each patient the efficacy of placebo, captopril (50 to 100 mg), ISDN (10 mg), and a combination of captopril (50 to 100 mg) and ISDN (10 mg) was assessed by repeated exercise treadmill tests performed before and 1, 2, 3 and 6 hours after administration of a single dose. A single-blind, randomized technique was applied. According to the mean data in the whole group of 14 patients, captopril alone produced no improvement in exercise duration to the onset of angina and to angina of moderate severity compared with placebo. The magnitude of ST-segment depression did not significantly change after captopril administration. ISDN alone significantly increased exercise duration to onset of angina and to angina of moderate severity (antianginal effect) and decreased the magnitude of ST-segment depression (antiischemic effect) 1 to 3 hours after administration. Combined administration of ISDN and captopril resulted in more expressed antianginal and antiischemic effects; at 2, 3 and 6 hours these effects with ISDN plus captopril were significantly more pronounced than those with ISDN alone. According to individual data, the most marked potentiation of ISDN efficacy was observed in patients who had poor response to ISDN alone. In all 6 patients in whom ISDN alone was ineffective, after the addition of captopril the desired antianginal effect was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does captopril produce an antianginal effect in patients with stable exercise-induced angina pectoris?

Captopril (C), isosorbide dinitrate (ID), and nifedipine (N) were evaluated for antianginal effects (AAE) in 12 patients with ischemic heart disease. The effects were assessed by treadmill exercise tests performed before and repeatedly 1, 2, 3, and 6 hours after the single dose of a drug or placebo. C, ID, and N were given in doses of 50, 10, and 20 mg, respectively. The drugs were equally effective in lowering systolic blood pressure at rest. Unlike ID and N, C failed to affect the duration of exercise testing until an anginal episode occurred and the magnitude of ST-segment depression at the same exercise intensity. ID and N caused a significant increase in the duration of exercise and a decrease in ST-segment depression during exercise 1-3 h later. An individual analysis has shown that C, ID, and N produced an antianginal effect only in 2, 9, and 10 patients, respectively. Thus, C is unable to show a substantial antianginal effect.     

Long-term treatment of stable angina pectoris with gallopamil]

BACKGROUND. The effects of long-term treatment with gallopamil 50 mg t.i.d were assessed in 8 patients, 7 males and 1 female, aged 47-69 years, with stable angina pectoris, positive exercise tests, coronary artery disease and no previous myocardial infarction. METHODS. Clinical and ECG parameters as well as exercise testing, 24-hour Holter and echocardiography were assessed before treatment, after 3 months, after 1 and 2 years of treatment, and following final wash-out. RESULTS. Comparing each treatment period to baseline, a significant decrease in resting heart rate (from 66 +/- 9 beats/min at baseline to 56 +/- 7 beats/min after 3 months [p < 0.01], 59 +/- 8 beats/min after 1 year [p < 0.05] and 58 +/- 9 beats/min after 2 years [p < 0.05]), systolic (from 162 +/- 19 mmHg at baseline to 147 +/- 12 mmHg after 3 months [p < 0.05], 146 +/- 20 mmHg after 1 year [p < 0.01] and 146 +/- 27 mmHg after 2 years [p < 0.05]), and diastolic (from 89 +/- 6 mmHg to 82 +/- 7 after 3 months [p < 0.05], 82 +/- 4 after 1 year [p < 0.05] and 83 +/- 4 after 2 years [p < 0.05]) blood pressure was observed. Exercise time significantly improved (from 596 +/- 209 seconds to 802 +/- 66 seconds after 3 months [p < 0.01], 710 +/- 167 seconds after 1 year [p < 0.05] and 723 +/- 125 seconds after 2 year [p < 0.05]), while heart rate and rate-pressure product at peak exercise did not change. The number of ischemic episodes and the total ischemic time per 24 hours significantly decreased (from 35 +/- 15 min to 12 +/- 10 min after 3 months [p < 0.05], 10 +/- 8 min after 1 year [p < 0.05] and 11 +/- 9 min after 2 years [p < 0.05]). Ejection fraction increased (from 66 +/- 10% to 77 +/- 7% after 3 months [p < 0.01], 80 +/- 5% after 1 year [p < 0.01] and 80 +/- 3% after 2 years [p < 0.01]), while contractility, as expressed by the end-systolic stress/end systolic volume ratio remained unchanged. No serious side-effects or biochemical abnormalities developed. CONCLUSIONS. Gallopamil appears to be safe, well tolerated and effective in the long term control of angina pectoris; its effects are fully developed at 3 months and persist unchanged after 2 years. For its hypotensive action and the lack of significant effects on myocardial contractility, gallopamil appears to be potentially useful in patients with associated angina and hypertension and in patients with impaired left ventricular function.     

The effects of sublingual administration of captopril on parameters of exercise test and neurohormonal activation in patients with stable angina pectoris

A prospective randomized, double-blind, and placebo-controlled study was designed to investigate the effects of sublingual administration of captopril on the parameters of exercise test and neurohormonal activation in patients with stable angina pectoris. A total of 31 patients (28 male, 3 female; mean age 55.4±9.4 years) took part in the study. Coronary angiography and left ventriculography were performed in all cases and the patients were classified according to the ejection fraction (EF). Following sublingual placebo or 25 mg captopril, plasma levels of renin, angiotensin II, norepinephrine, and serum aldosterone levels were measured at rest and maximal exercise. test was performed. Hormone levels were remeasured immediately after the exercise. The same procedure was repeated the next day using captopril or placebo. Sublingual captopril administration increased the time to angina, the time to 1 mm ST depression, maximal exercise capacity, maximal exercise duration and decreased maximal ST depression, maximal systolic blood pressure, and maximal double product (p<0.001–0.01). After the maximal exercise test following captopril, the % difference of angiotensin II, aldosterone, and norepinephrine levels was found to be significant lower and the % difference of the renin level was found to be significantly higher than those of placebo (p<0.001). The effects of sublingual captopril on exercise parameters were additionally assessed in different left ventricular systolic function subgroups. The favorable effects were more prominent in cases with left ventricular systolic dysfunction. There were no adverse effects related to sublingual captopril use. As a result, sublingual administration of captopril improved the parameters of maximal exercise test and suppressed the neurohormonal activation during exercise. We suggest that sublingual captopril may be used effectively before planned daily activities in patients with stable angina pectoris.     

Pathophysiology of stable angina pectoris

The pathophysiology of stable angina is discussed with respect to anatomic substrate, coronary and systemic hemodynamic mechanisms, the dynamic nature of coronary artery stenoses, and determinants of myocardial oxygen consumption. Cellular mechanisms involved in ischemia and the transduction of these changes into angina are also reviewed.     

Nitroglycerin in chronic stable angina pectoris

Recent evidence suggests that traditional approaches to the use of nitroglycerin (NTG) in patients with chronic stable angina should be reconsidered. Studies of the time to onset of hemodynamic effects of sublingual NTG suggest that the first detectable effect, on left ventricular end-diastolic pressure, occurs at a mean of 90 seconds after administration. By timing the duration of exertional angina after formal exercise testing, one can show that, on average, chest pain is gone within 2 minutes. Thus, in many patients, it is unlikely that sublingual NTG can further shorten episodes of exertional angina. The value of sublingual NTG is greater when patients exercise beyond the onset of pain, when patients have more protracted episodes of exertional pain and when there is a need to resume immediately the activity that brought on the angina. With respect to angina prophylaxis, the pioneering studies of Parker and co-workers have now been amply confirmed. Continuous nitrate administration by oral, transdermal or intravenous routes results in substantial, albeit incomplete, tolerance. Tolerance occurs even when high plasma concentrations are achieved and persist over time. Tolerance can eliminate responsiveness to sublingual NTG. Preliminary evidence suggests that tolerance to the antianginal effects of NTG at maximal exercise may be more marked than tolerance to the effects of NTG on silent ischemia at submaximal activity levels. The significance of this dissociation in time course and its implications are unclear at this time. Three potential strategies exist for avoiding NTG tolerance in patients with chronic stable angina. Administration of a thiol donor has been shown to reverse some hemodynamic manifestations of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The anti-ischemic effect of gallopamil-retard in comparison with nifedipine-retard in stable angina pectoris]

To assess the antiischemic efficacy of slow-release (SR) gallopamil, 100 mg b.i.d., versus slow-release (SR) nifedipine, 20 mg b.i.d., 24 patients with chronic stable angina underwent symptom-limited bicycle ergometer exercise stress tests in a randomized, placebo-controlled, double-blind, cross-over protocol. Both medications caused a significant reduction in anginal attack frequency and nitroglycerin consumption as compared to placebo; similarly, exercise tolerance was augmented in association with a considerable reduction in ischemia-induced ST-segment depression. The antiischemic effect of gallopamil (SR) was marginally superior to that of nifedipine (SR). Since the incidence of adverse effects was also less with gallopamil (SR) this drug exhibited a more favorable risk-benefit ratio relative to nifedipine (SR).     

Acute and sustained effects of isosorbide 5-mononitrate in stable angina pectoris

Isosorbide 5-mononitrate (IS 5-MN) is an active metabolite of isosorbide dinitrate and is widely used as an antianginal agent. The acute and subacute (2 weeks) effects of IS 5-MN, 40 mg twice daily, were evaluated in 18 patients with stable angina pectoris using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were 2 phases of 2 weeks each in which patients received placebo or active IS 5-MN. Acute testing (8 patients) was performed 2 hours after the first dose and subacute testing 2 hours after the morning dose on day 14. Acute testing showed an increase in exercise time from a mean (+/- standard error of mean) of 8.2 +/- 0.6 minutes to 11.1 +/- 0.5 minutes (p less than 0.001) after a single dose of IS 5-MN. Time to 1 mm of ST depression increased significantly and peak exercise ST-segment depression decreased significantly. Rest and peak exercise heart rate increased significantly during acute testing with IS 5-MN; blood pressure did not change significantly. After 2 weeks of therapy, exercise time had not changed (9.9 +/- 0.6 with placebo to 9.7 +/- 0.6 minutes). The beneficial effects on ST-segment variables were sustained at 2 weeks. The data suggest that there is an attenuation of effect with respect to exercise time and sustained beneficial effect on the ST-segment variables. This may be a result of development of partial tolerance to IS 5-MN after 2 weeks of therapy.     

Coronary artery stenting in unstable angina pectoris: a comparison with stable angina pectoris

OBJECTIVE: To compare early complication rates in unselected cases of coronary artery stenting in patients with stable v unstable angina. SETTING: Tertiary referral centre. PATIENTS: 390 patients with stable angina pectoris (SAP) and 306 with unstable angina (UAP). Patients treated for acute myocardial infarction (primary angioplasty) or cardiogenic shock were excluded. INTERVENTIONS: 268 coronary stents were attempted in 211 patients (30.3%). Stents used included AVE (63%), Freedom (14%), NIR (7%), Palmaz-Schatz (5%), JO (5%), and Multilink (4%). Intravascular ultrasound was not used in any of the cases. All stented patients were treated with ticlopidine and aspirin together with periprocedural unfractionated heparin. RESULTS: 123 stents were successfully deployed in 99 SAP patients v 132 stents in 103 UAP patients. Failed deployment occurred with nine stents in SAP patients, v four in UAP patients (NS). Stent thrombosis occurred in four SAP patients and 11 UAP patients. Multivariate analysis showed no relation between stent thrombosis and clinical presentation (SAP v UAP), age, sex, target vessel, stent length, or make of stent. Stent thrombosis was associated with small vessel size (p < 0.001) and bailout stenting (p = 0.01) compared with elective stenting and stenting for suboptimal PTCA, with strong trends toward smaller stent diameter (p = 0.052) and number of stents deployed (p = 0.06). Most stent thromboses occurred in vessels < 3 mm diameter. CONCLUSIONS: Coronary artery stenting in unstable angina is safe in vessels >/= 3 mm diameter, with comparable initial success and stent thrombosis rates to stenting in stable angina.