Clinical aspects of ACE inhibition in patients with acute myocardial infarction

Summary The purpose of the present article was to review the current evidence on the use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI). This article is based on published information as well as on our personal experience derived from an extensive analysis of the SMILE study. All the randomized trials have been included irrespective of the primary endpoint, and the results are presented in terms of either hemodynamic or clinical benefit. Short- and long-term treatment with ACE inhibitors in patients with acute MI results in a significant reduction in mortality, which is more evident in high risk patients (i.e., patients with left ventricular dysfunction, congestive heart failure on admission, or anterior myocardial infarction). Development and progression of congestive heart failure after myocardial infarction was significantly reduced by ACE inhibition, which also reduced the rate of reinfarction, the need for revascularization procedures, as well as the occurrence of ventricular arrhythmias, probably through a mechanism involving some drug-dependent effects. In conclusion, the available data strongly support a wide benefit associated with the use of ACE inhibitors in patients with high-risk acute MI.     

Onset of action of captopril,enalapril, enalaprilic acid and lisinopril in normal man

Summary The effects of orally administered captopril, enalapril and lisinopril on plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANGII) and renin (PRC) were studied over a period of 6 hours in 6 normal subjects. A further 4 subjects received intravenous enalapril and enalaprilic acid (enalaprilat). Captopril (25 mg) by mouth caused a fall in pANGII that reached a nadir 30 to 40 minutes after administration but an effect was hardly apparent after 6 hours. Enalapril (10 mg) by mouth had less marked effects on pACE and pANGII with a decline in levels first apparent 1 hour after administration and the lowest levels reached between 3 and 6 hours. Lisinopril (10 mg) produced a progressive fall in pACE and pANGII from 1 hour to reach the lowest values 6 hours after treatment. Intravenous enalaprilat (5 mg) produced an immediate sustained fall in both pACE and pANGII but intravenous enalapril (7 mg) had a biphasic inhibitory effect.     

A large-scale trial of captopril for mild to moderate heart failure in the primary care setting

A large-scale, prospective, 8-week, office-based study was conducted to evaluate the effects of adding captopril to a therapeutic regimen of diuretic and digoxin or diuretic alone in the management of patients with mild to moderate congestive heart failure (CHF). A total of 2218 primary care physicians evaluated 6669 patients over the study period for efficacy parameters, which included changes in a modified New York Heart Association (NYHA) functional classification, symptomatology, and daily activity levels. Overall, 63.8% of evaluated patients improved with regard to functional ability, with 19% improving two or more modified NYHA classes. Symptoms of CHF, including dyspnea on exertion, fatigue, and orthopnea and signs, including rales and peripheral edema, were reduced in 86% of these patients: 41.5% demonstrated mild improvement; 30.0%, moderate improvement; and 14.5%, marked improvement. Three parameters, with which patients reported having difficulty at study entry, were assessed serially to evaluate changes in functional capacity; 78.5% of patients reported an increased walking distance, 72.3% had increased capacity for climbing stairs, and 60.2% had improved capacity for individual recreational activities. Adverse experiences were reported in 18.1% of all patients; 4.9% of patients withdrew from the study because of an adverse effect. Combination therapy with captopril and diuretic for CHF was shown to be safe and effective regardless of patient age (less than 70 years vs. greater than or equal to 70 years), duration of heart failure (less than 1 year vs. greater than 1 year), presence of digoxin treatment, or the dosing schedule employed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of quality of life in a double-blind,randomized clinical trial of imidapril and captopril for hypertensive Chinese in Taiwan

Purpose. Although the role of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension has been well established, no data has been generated regarding the influence of ACE inhibitors for health-related quality-of-life (QOL) dimensions for Chinese patients. Materials. A double-blind, active-control, randomized clinical trial was used to compare the effects of two ACE inhibitors, imidapril and captopril, on quality-of-life dimensions in one outpatient clinic in one tertiary clinical-care facility. After a 2–3 week washout period with placebo, 59 patients with mild-to-moderate hypertension were randomly assigned to receive imidapril (5 to 10 mg per day) or captopril (25 to 50 mg twice per day) for 12 weeks. Patients completed the Short-form 36 (SF 36) health survey questionnaire, which evaluates 8 QOL dimensions, just before treatment, during the 8th week, and at the end of treatment (12th week). ANOVA for repeated measures was used to analyze the QOL-score changes over time and compare treatments, and to assess the interaction of treatment duration and group on these scores. Results. No significant differences were demonstrated for changes in blood-pressure, frequency of adverse effects and withdrawal of patients from the study comparing the two drugs. Significant improvement, however, was demonstrated for mental-component summary scores after 12 weeks of treatment for both drugs (P = 0.029). No significant differences were established for individual QOL dimensions comparing the two drugs. A significantly higher baseline systolic blood pressure was found in the participants who did not complete the questionnaire than in those who did. Conclusions. Similar and significant improvements were determined for the mental-component QOL summary scores for the two ACE inhibitors, imidapril and captopril, and no significant differences were demonstrated comparing treatments.     

Differential systemic and regional hemodynamic profiles of four angiotensin-I converting-enzyme inhibitors in the rat

Summary Angiotensin-converting enzyme (ACE) inhibitors decrease blood pressure by reducing systemic vascular resistance. That the peripheral vasodilating properties of ACE inhibitors might not be homogeneously distributed in all vascular beds and might differ from one drug to another has been investigated in the normotensive rat by the pulsed Doppler technique using the active components of four different ACE inhibitors: captopril, enalapril, perindopril, and ramipril.Systemic (cardiac output and blood pressure) and regional (kidney, mesentery, hindquarter) hemodynamic responses to saline or to cumulative bolus injections (0.01–1 mg/kg) of captopril, enalaprilat, perindoprilat, or ramiprilat were continuously monitored. The effects of successive bolus injections (0.3–300 ng/kg) of angiotensinII were also investigated. The four ACE inhibitors produced an almost complete blockade of plasma angiotensin-II converting-enzyme activity (83%, 100%, 100%, and 100%, respectively), induced dose-dependent decreases in mean blood pressure, did not significantly affect cardiac output, and reduced total peripheral and mesenteric vascular resistances to the same extent. Hindlimb vascular resistance was identically decreased, but to a lower extent than total peripheral resistance by enalaprilat, perindoprilat, and ramiprilat, whereas it was increased by captopril at low doses only. Renal resistance was markedly decreased by the four drugs, and éspecially by captopril. The decreasing rank order for ACE-inhibitor-induced vasodilation is exactly the same (renal>total peripheral=mesenteric >hindlimb vascular resistances) as that of angiotensin-II-induced regional vasoconstriction, indicating that the vasodilator properties of ACE inhibitors are mainly due to angiotensin-II vasomotor tone suppression. None of the investigated compounds significantly affected mesenteric and hindlimb blood flows, except captopril, which lowered the latter significantly. Finally, the four drugs increased renal blood flow markedly.Thus, the four drugs exhibited different regional vasodilating patterns, those of enalaprilat, perindoprilat, and ramiprilat being almost similar, while that of captopril was different.     

Effect of benazepril on myocardial ischaemia in patients with chronic stable angina pectoris

The anti-ischaemic properties of benazepril, a non-sulfhydrylinhibitor of angiotensin-converting enzyme, were assessed in20 patients with chronic stable angina pectoris, by repeatedexercise tests and repeated 72-h ambulatory electrocardio-graphicmonitoring. The study was a double-blind, placebo-controlledcross-over; 11 patients received benazepril 10 mg b.i.d. andnine received 20 mg b.i.d. All patients had a positive treadmillstress test and at least three ischaemic episodes during 24h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exerciseduration, the time taken to reach 1 mm ST depression. Similarfindings were observed during treatment with 20 mg b.i.d. Benazeprilat a dose of 10 mg b.i.d. was ineffective in improving ischaemicparameters during daily activities. However, among the ninepatients who received 20 mg b.i.d. the number of ischaemic episodeswas reduced from 142 to 103, and the total duration of ischaemiawas reduced from 1099 to 531 min. The number of weekly anginalattacks was reduced from 58 to 33, and the weekly sublingualnitroglycerin tablets consumption was reduced from 31 to 14.When the two doses (10 mg and 20 mg) were combined (N = 20),the number of ischaemic episodes was reduced from 314 to 260(P= 0.074), and the duration of ischaemia was reduced from 3453to 2514 min (P = 0.072).     

Effects of early captopril therapy after myocardial infarction on the incidence of late potentials

Background: Late potentials (LP) on signal‐averaged electrocardiography (SAECG), recorded 6 to 30 days after an acute myocardial infarction (AMI), identify patients at risk for late arrhythmic events. Angiotensin‐converting enzyme (ACE) inhibitors have been shown to reduce ventricular remodeling and cardiovascular mortality after AMI. Hypothesis: The aim of this study was to investigate the effect of early (< 24 h) administration of captopril on the presence of LP on Days 6–30 after AMI. Methods: The study included 117 patients with a first AMI; 63 patients (53 men and 10 women, aged 59±12 years), 35 with an anterior and 28 with an inferior AMI (44 thrombolyzed), received early captopril therapy. The control group consisted of 54 age‐matched patients (39 men and 15 women, aged 60 ± 12 years), 19 with an anterior and 35 with an inferior AMI (31 thrombolyzed, p = NS), who did not receive early therapy with an ACE inhibitor. The mean left ventricular ejection fraction was similar in both groups (48 vs. 46%). Time domain analysis of SAECG was performed using a band‐pass filter of 40–250 Hz. Late potentials were considered present if any two of three criteria were met: (1) Filtered QRS duration (QRSD) > 114 ms, (2) root‐mean‐square voltage of the last 40 ms of the QRS complex (RMS) > 20 m?V, and (3) duration of low amplitude (< 40 m?V) signal of the terminal portion of the QRS (LAS) > 38 ms. Results: In the two groups of patients there were no differences in mean values of SAECG parameters. No patient was receiving any antiarrhythmic drugs. In the captopril group LPs were present in 9 of 63 patients (14%) and in the control group in 17 of 54 patients (31 %) (p =0.046). There was no difference in the number of patients with a patent infarct‐related artery in the two groups (76 vs. 59%). Conclusion: Captopril treatment early after an AMI reduces the incidence of LPs recorded on Days 6–30 and may thus favorably affect the arrhythmogenic substrate.     

The effects of propranolol on myocardial perfusion and metabolism during acute regional ischaemia

The unique physical properties of the short-lived inert and freely diffusing isotope ^81mkrypton allow a continuous observation to be made of regional myocardial perfusion. Eighteen dogs were anaesthetised and a reversible snare placed on the left anterior descending coronary artery (LAD). ^81mKrypton was used to study regional myocardial perfusion, and myocardial metabolism was assessed using the epicardial ECG and release of creatine kinase activity (CK). Six dogs did not undergo LAD occlusion (“sham operated”); in six other dogs the LAD was occluded (controls), and another six dogs were given propranolol, 0.5 mg/kg, 20 min after LAD occlusion. All the parameters were measured before and for 5 h after LAD occlusion. When compared to controls, dogs treated with propranolol showed significant improvement (p<0.01) in regional myocardial perfusion; smaller loss of electrically active myocardium for any given degree of early ST-segment elevation; and a delay in the release of CK activity from a local coronary vein. These results suggest that propranolol exerts a beneficial effect following the development of acute myocardial infarction.     

Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarction: Randomized, placebo-controlled substudy of ISIS-4

The antiarrhythmic effect of oral captopril was studied duringthe early (day 3) and late (day 14) phase of acute myocardialinfarction among 304 patients in a randomized placebo-controlledsubstudy of ISIS-4. Ventricular arrhythmias (ventricular ectopic beats per hour)occurred significantly less frequently among captopril-allocatedpatients than among those allocated placebo at day 3 (logarithmicscale: 0·48 ± 0·8 captopril vs 0·84± 1·3 placebo; P<0·003) and at day 14(0·51 ± 1·0 vs 0·77 ± 1·3;P<0·05). The number of patients with frequent ventriculararrhythmias (more than 10 ventricular ectopic beats per hour)was also significantly lower among those allocated captoprilat day 3 (7·3% vs 14·4% P<0·05) andat day 14 (7·3% vs 14·8%; P<0·05). These results support the hypothesis that the activation ofthe renin-angiotensin-aldosterone and sympathetic system mayunderlie heart rhythm disturbances in acute myocardial infarction,and that early use of converting enzyme inhibitor therapy mayameliorate these disturbances. (Eur Heart J 1996; 17: 1506–1510)     

Effect of captopril on left ventricular end-systolic pressure-volume and stress-shortening relations in severe cardiac failure

The effects of captopril on cardiovascular dynamics and left ventricular (LV) contractility were studied in 11 patients with severe congestive heart failure and very poor global LV function. Pressures were measured using a flow-guided catheter, cardiac output by thermodilution, and LV contraction and ejection fraction by simultaneous radionuclide angiography. Ventricular loading conditions were altered by sublingual isosorbide dinitrate to facilitate construction of LV pressure-volume and stress-shortening curves. Captopril decreased mean arterial pressure (p less than 0.02) and systemic vascular resistance, while stroke and cardiac index increased in most patients. Left ventricular ejection fraction increased from 18 +/- 5 to 22 +/- 7% (p less than 0.05), but contractility, assessed from end-systolic pressure-volume and end-systolic pressure-shortening relations, was unchanged or decreased slightly. Heart rate and double product also tended to decrease. In contrast, arteriovenous oxygen difference widened and calculated total oxygen consumption increased during captopril therapy (p less than 0.05). The study showed that captopril improved forward blood flow, total oxygen extraction, and LV ejection fraction following the decrease impedance to LV emptying but not at the expense of an increase in ventricular contractility. This makes captopril an attractive drug for patients with end-stage cardiac failure and a severely damaged myocardium.     

The Influence of Chronic Captopril Treatment and its Withdrawal on Endothelium-Dependent Relaxation

The current experiments were designed to explore the relationship between the renin angiotensin system (RAS) and prostanoid formation in aortic ring preparations from spontaneously hypertensive rats (SHR). A further aim was to examine the mechanisms responsible for the reversal of the impaired acetylcholine (ACh) mediated relaxation induced by chronic administration of the angiotensin converting enzyme inhibitor captopril and the relationship of the ACh response to blood pressure. Rats were administered captopril (100 mg/kg/day) and their blood pressures monitored from 5 to 17 weeks of age. ACh-mediated relaxation was determined in aortic ring preparations from untreated and treated rats, and drug withdrawn rats. The influence of indomethacin, saralasin, SQ29548 and captopril on ACh-mediated responses was determined. It was found that chronic captopril treatment produced a marked suppression of the development of hypertension in the SHR. After the withdrawal of the drug the blood pressure remained significantly lower than in untreated animals for 4 weeks. ACh relaxation was impaired in SHR ring segments; this was reversed with captopril treatment and returned to the impaired state upon withdrawal of the drug. In vitro inhibition of the RAS did not significantly influence ACh relaxation. In contrast, impairment of the prostanoid system in vitro reversed the impaired relaxation. The results suggest that the influence of captopril on enhancing ACh relaxation in the SHR does not involve an acute interaction of local angiotensin II synthesis with prostanoid mechanisms. Importantly, the results highlight a dissociation between the impaired ACh relaxation and elevated blood pressure in the SHR.     

血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

目的　探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂 (ACEI )后发生咳嗽的机制。方法　应用聚合酶链反应 (PCR) ,检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶 (ACE)基因多态性 ,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性。结果　ACEI所致咳嗽组ACE基因Ⅱ型的频率为4 0 % ,显著高于无咳嗽组 (2 0 % ,P <0 0 5 ) ,Ⅰ等位基因频率为 6 0 % ,显著高于无咳嗽组 (4 1% ,P <0 0 1)。两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低。咳嗽组血清ACE水平显著低于无咳嗽组 (P <0 0 0 1) ,血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为 81%和 78%。结论　老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关。     

Angiotensin-converting enzyme inhibition by quinapril blocks the albuminuric effect of atrial natriuretic peptide in Type 1 diabetes and microalbuminuria.

AIMS: This study examined the effect of angiotensin-converting enzyme inhibition, administered at doses with no effect on systemic blood pressure, on the albuminuric action of atrial natriuretic peptide (ANP). METHODS: Seven Type 1 diabetic patients with established microalbuminuria participated in a two limb, single-blind, placebo controlled study. Subjects were administered quinapril 10 mg daily or placebo for 7 days prior to study. On the study day, subjects were euglycaemic clamped and subsequently fluid loaded (20 ml/kg tap water orally plus urinary losses). At steady state diuresis, a 1 h intravenous infusion of ANP 0.05 mg.kg(-1) x min(-1) was administered. Urine was collected at 15-min intervals for estimation of albumin-creatinine ratio (ACR). Results were analysed by ANOVA. RESULTS: Baseline mean arterial pressure was similar after pre-treatment with quinapril and placebo (98.7 +/- 3.8 vs. 100 +/- 4.5 mmHg, mean +/- SD, P > 0.5), and was unaltered by ANP infusion on either study day. Baseline ACR was similar on quinapril and placebo (P = 0.13). ANP infusion induced a rise in urine ACR with placebo (58.4 +/- 40.2 to 393.6 +/- 262.9 mg/mmol, P = 0.006), but not with quinapril (29.3 +/- 10.7 to 81.5 +/- 43 mg/mmol, P = 0.15). The urine ACR response to ANP infusion was higher with placebo than with quinapril (P = 0.02). CONCLUSIONS: Quinapril blocks the albuminuric effect of intravenous infusion of ANP in subjects with Type 1 diabetes mellitus and established microalbuminuria. This action is independent of changes in mean arterial pressure and creatinine clearance.     

Cardiac arrhythmias are ameliorated by local inhibition of angiotensin formation and bradykinin degradation with the converting-enzyme inhibitor ramipril

Summary We investigated the influence of the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac arrhythmias in guinea pigs and rats. Ramiprilat, the active moiety of ramipril, did not influence action potentials of isolated guinea-pig papillary muscle or rabbit sinus node, thereby excluding cellular electrophysiological evidence of anti-arrhythmic properties. Ramipril protected against cardiac arrhythmias induced by digoxin infusion in guinea pigs. This effect was comparable with that of lidocaine. In isolated perfused ischemic working rat hearts, angiotensin (ANG) I (3×10^–9 M/l) and ANG II (1×10^–9 M/l) aggravated reperfusion arrhythmias, accompanied by deterioration of cardiodynamic and metabolic events. Bradykinin (BK) (1×10^–10–1×10^–8 M/l), in contrast, protected against reperfusion arrhythmias, which corresponded to an increase in energy-rich phosphates and glycogen stores and a decrease in lactate levels in myocardial tissue. Identical changes were seen in hearts from rats pretreated with ramipril (1 mg/kg PO) or perfused with ramiprilat (2.58 ×10^–7–2.58×10^–5 M/l). Local ACE inhibition in these ischemic hearts antagonized ANG I but not ANG II effects and enhanced BK effects. The BK antagonist D-Arg-(Hyp², Thi^5,8, D-Phe⁷) BK abolished the beneficial effects of BK, ramipril, and ramiprilat. Increased concentrations of BK or ramiprilat were able to reverse the antagonism.The antiarrhythmic agent nicainoprol, a fast-sodiumchannel blocking drug (class Ib), also protected isolated rat hearts against reperfusion arrhythmias, but was without beneficial effects on cardiac hemodynamics and biochemical parameters, in contrast to the ACE inhibitor.These results suggest that the beneficial effects of the ACE inhibitor ramipril on digoxin and reperfusion arrhythmias are not mediated by their direct actions on ionic channels in the cell membrane. It seems that other factors are responsible for its beneficial effects on reperfusion arrhythmias, cardiac function, and metabolism, which are associated with a reduction in ANG II generation and BK degradation by local ACE inhibition in the heart.     

Structural pathways and prevention of heart failure and sudden death

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.     

Captopril in acute myocardial infarction: Beneficial effects on infarct size and arrhythmias

It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5–2.0 mg captopril/h I.V., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (—0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.     

The role of prostaglandins in mediating the effects of angiotensin converting enzyme inhibitors and other antihypertensive drugs

Summary This review considers the hypothesis that angiotensin converting enzyme (ACE) inhibitors and other antihypertensive drugs may reduce blood pressure by altering the balance of vasoconstrictor and vasodilator hormones. Most cases of essential hypertension are characterized by increased vascular resistance. Since vascular resistance can be viewed as a net balance of offsetting vasoconstrictor and vasodilator neurohumoral forces, and since angiotensin II and norepinephrine can stimulate the synthesis of vasodilator prostaglandins that can in turn counteract peripheral vasoconstriction, we measured changes in vasoconstrictor (angiotensin II) and vasodilator (PGE₂) hormones after giving different antihypertensive drugs. We found that the sulfhydryl containing converting enzyme inhibitor captopril increased vasodilator prostaglandin production (PGE₂-metabolite) both acutely and chronically. This increase in PGE₂-metabolite was not seen with the non-sulfhydryl converting enzyme inhibitor, enalapril.Stephen L. Swartz is the recipient of a Veterans Administration Career Development Award as a Research Associate in Endocrinology. These studies were also supported by an NIH grant: R01 HL35162     

A 3-month double-blind cross-over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure.

The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post-infarction (6-24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double-blind cross-over design with 3-month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure.     

长期抗神经内分泌治疗对高血糖心肌梗死患者左心室功能的影响

目的观察长期抗神经内分泌治疗对高血糖心肌梗死患者神经内分泌激素及左心室功能的影响。方法将入选的65例心肌梗死患者,分为血糖正常组(34例)和高血糖组(31例),给予美托洛尔加血管紧张素转换酶抑制剂(ACEI)治疗,分别于治疗前和治疗后6个月采血检测血浆神经内分泌激素的水平。随访2年分别于治疗前和治疗后行超声心动图检测,观察两组患者在用药前后心室重构的逆转、左心室功能的变化。结果使用美托洛尔并ACEI可以降低血糖正常组和高血糖组患者的血浆肾素、血管紧张素Ⅱ水平,血浆肾素活性、血管紧张素Ⅱ浓度降低,差异有显著性意义(P<0.05)。血糖正常组患者治疗后左心室射血分数(LVEF)好转(P<0.05),高血糖组患者LVEF虽有好转,但差异无显著性意义。结论抗神经内分泌治疗可以降低心肌梗死患者的血浆肾素、血管紧张素Ⅱ水平。