enalapril and Coronary-Artery-Disease

This study aimed to analyze the effect of felodipine combined with enalapril in the treatment of patients with essential hypertension and coronary artery disease. Also, the effect of these medicines was evaluated on the peripheral blood Salusin-β, Apelin levels, and PON1 gene expression. For this purpose, 110 patients with essential hypertension combined with coronary heart disease, admitted to the hospital from January 2019 to January 2021, were selected and randomly divided into two groups. The control group was given felodipine treatment alone, and the study group was treated with combined application of felodipine and enalapril. The treatment effect, peripheral blood Salusin-β, Apelin, PON1 gene expression, and the safety of medication were compared between the two groups. The results showed that the post-treatment systolic blood pressure in the study group was 119.77 ± 5.23 mm Hg and diastolic blood pressure was 86.84 ± 5.42 mm Hg, both of which were significantly lower than those in the control group (127.81 ± 6.92 mm Hg and 95.13 ± 6.08 mm Hg), with statistically significant differences (p<0.05). The effective rates of the study group and the control group were 92.73% and 74.54% respectively, with statistically significant differences (P<0.05). The post-treatment peripheral blood Salusin-βlevel in the study group was 3.77±0.53mmol/L, and Apelin was 1.94±0.58μg/L, with statistically significant differences compared to the control group (P<0.05). The PON1 gene expression in the study group was higher than those in the control group after treatment (P<0.05). Also, the results showed that there was no statistical difference in adverse reactions between the two groups (P>0.05). According to these results, the combination of felodipine and enalapril in patients with essential hypertension combined with coronary artery disease can effectively lower the patients' blood pressure and improve their peripheral blood Salusin-β, Apelin levels, and PON1 gene expression, thus enhancing the patients' therapeutic effect with few adverse effects and high safety.

Topics: Apelin; Aryldialkylphosphatase; Blood Pressure; Coronary Artery Disease; Enalapril; Essential Hypertension; Felodipine; Gene Expression; Humans; Hypertension

Cardiovascular (CV) disease fatality rates are higher for women compared with men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post hoc analysis to determine whether there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled type 2 diabetes and without clinical evidence of obstructive CAD. We found that women had a higher rest MBF, lower CFR, and worse diastolic function compared with men. In addition, rest MBF was positively correlated with worse diastolic function in women. We previously showed that mineralocorticoid blockade improved CFR in men and women with type 2 diabetes, implicating aldosterone in the pathophysiology of coronary microvascular dysfunction. We therefore examined aldosterone levels and found that women had larger increases in aldosterone in response to an angiotensin-II infusion than did men. In conclusion, among individuals with type 2 diabetes and good cardiometabolic control, women had worse myocardial perfusion and diastolic function compared with men. The greater aldosterone responsivity in women may be a mechanism for this sex effect.

Topics: Adolescent; Adult; Aged; Blood Flow Velocity; Coronary Artery Disease; Coronary Circulation; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Sex Factors; Young Adult

Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF.. We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly.. Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cause of Death; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Enalapril; Female; Global Health; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Revascularization; Prospective Studies; Stroke Volume; Survival Rate; Tetrazoles; Valsartan

To investigate the relationship between visit-to-visit blood pressure variability (BPV) and the progression of both carotid and coronary artery disease (CAD).. Data from two cardiovascular endpoint studies [Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) and Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)] were analysed separately. Systolic BPV was assessed as within-subject standard deviation of systolic BP across visits from 12-weeks onwards. Follow-up was 24 months (NORMALISE) or 36 months (PREVENT). Any association between BPV and progression of atherosclerosis was assessed using quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), or B-mode ultrasound (depending on study). Patients from NORMALISE (n = 261) and PREVENT (n = 688 for QCA; n = 364 for ultrasound) were stratified within study according to median systolic BPV. No significant difference in change of minimal luminal diameter (by QCA in PREVENT) or change in percent atheroma volume or normalized total atheroma volume (by IVUS in NORMALISE) was detected for subjects with low BPV (BPV < median) compared with high BPV (BPV ≥ median), regardless of treatment. In PREVENT, a significantly greater reduction in maximum carotid intima-media thickness (IMT) (left and right common carotid artery far wall) was observed for patients with BPV < median compared with those with BPV ≥ median [least squares mean difference 0.06 (95% confidence interval 0.01, 0.11); P = 0.0271], after adjusting for treatment, carotid artery segment (left or right), baseline maximum carotid IMT, and other baseline and cardiovascular risk factors/covariates.. In patients with existing CAD and well-controlled BP, visit-to-visit BPV was not associated with progression of coronary atherosclerosis; however, a significantly greater reduction in maximum carotid IMT was observed for patients with low BPV.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Blood Pressure; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Disease Progression; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Ultrasonography, Interventional; Vasodilator Agents

Favorable effects of angiotensin-converting enzyme (ACE) inhibitor treatment on the incidence of cardiovascular and cerebrovascular mortality and morbidity are not limited to patients with elevated blood pressure. As suggested by our previous results, the physicochemical and pharmacokinetic differences between drugs may markedly contribute to the strength of pleiotropic effects of ACE inhibitors.. The present study was aimed at comparing the effects of serum- and tissue-type ACE inhibitors on monocyte release of proinflammatory cytokines in normotensive patients with stable coronary artery disease. The participants were randomized to 90-day treatment with enalapril (20 mg daily, n = 29), perindopril (4 mg daily, n = 27) or placebo (n = 28). Plasma levels of lipids, glucose, insulin and high sensitivity C-reactive protein (hsCRP), as well as monocyte release of proinflammatory cytokines were determined before and after 30 days of therapy, and at the end of the treatment.. Lipopolysaccharide-stimulated monocytes from normotensive patients with stable coronary artery disease released significantly more TNF-α, interleukin-1β and monocyte chemoattractant protein-1 in comparison with monocytes from 23 matched control subjects. Their baseline hsCRP levels were also higher. Perindopril reversed the disease-induced changes in cytokine release and reduced plasma hsCRP, while the effect of enalapril was much more limited. The effect on both drugs on cytokine release was stronger in insulin-resistant than insulin-sensitive subjects.. Our results indicate that perindopril is superior to enalapril in producing monocyte-suppressing and systemic anti-inflammatory effects in normotensive patients with coronary artery disease. This action may contribute to the clinical effectiveness of tissue ACE inhibitors in the therapy of atherosclerosis-related disorders, particularly in insulin-resistant subjects.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Blood Pressure; Cells, Cultured; Chi-Square Distribution; Coronary Artery Disease; Cytokines; Enalapril; Female; Humans; Inflammation Mediators; Insulin Resistance; Lipids; Male; Middle Aged; Monocytes; Perindopril; Poland; Time Factors; Treatment Outcome

Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study.. The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo.. Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (-4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary atheroma (Δ percent atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent atheroma volume was significantly less in subjects taking statins at baseline (-2.5%, P = .0008).. In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease atheroma progression by mechanisms other than those reflected by these plasma biomarkers.

Topics: Amlodipine; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Coronary Thrombosis; Disease Progression; Enalapril; Humans; Interleukin-18; Matrix Metalloproteinase 9; Neopterin; Receptors, Interleukin-1; Secondary Prevention; Ultrasonography, Interventional

The clinical effectiveness of angiotensin-converting enzyme (ACE) in the prevention and treatment of cardiovascular disorders partially results from its anti-inflammatory action. No previous study has investigated the effect of any ACE inhibitor on lymphocyte cytokine release. In this study, we compared the effects of serum- and tissue-type angiotensin-converting enzyme inhibitors on systemic inflammation and lymphocyte secretory function in normotensive patients with stable coronary artery disease. The study included 134 patients with coronary artery disease who were randomized into one of three groups and treated with enalapril (20 mg/d, n = 47), perindopril (4 mg/d, n = 45) or placebo (n = 42), respectively. The control group included 40 age-, sex- and weight-matched healthy subjects. The plasma lipid profile, glucose metabolism markers, hsCRP and lymphocyte cytokine release were examined at the beginning of the study and after 30 and 90 days of treatment. Phytohemagglutinin-stimulated T cells released significantly more interleukin-2, interferon-γ and TNFα than the lymphocytes of control subjects. Neither enalapril nor perindopril treatment was associated with any significant changes in blood pressure. Perindopril treatment inhibited lymphocyte cytokine release and systemic inflammation, while the effect of enalapril was insignificant. Perindopril, and, to a lesser extent, enalapril, strongly reduced lymphocyte cytokine release in insulin-resistant but not insulin-sensitive subjects. Our results indicate that perindopril is superior to enalapril in producing lymphocyte-suppressing and systemic anti-inflammatory effects in normotensive coronary artery disease patients. These effects may contribute to a reduction in the vascular risk of this group of patients, particularly in those subjects who are resistant to insulin, when these patients are treated with tissue-type angiotensin-converting enzyme inhibitors.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Case-Control Studies; Coronary Artery Disease; Cytokines; Double-Blind Method; Enalapril; Female; Humans; Insulin Resistance; Lipids; Lymphocytes; Male; Middle Aged; Perindopril; Phytohemagglutinins; Prospective Studies; Time Factors

The TLR4 (Toll-like receptor 4) signal plays an important role in immunity in CAD (coronary artery disease). miR-146a/b (where miR is microRNA) regulates the TLR4 downstream molecules IRAK1 (interleukin-1-receptor-associated kinase 1) and TRAF6 (tumour-necrosis-factor-receptor-associated factor 6). It has also been reported that statins and RAS (renin-angiotensin system) inhibition and have anti-atherosclerotic properties. In the present study, we have investigated whether miR-146a/b was expressed with the TLR4 signal in CAD patients, and whether combined treatment with a statin and RAS inhibition might affect these levels. A total of 66 patients with CAD and 33 subjects without CAD (non-CAD) were enrolled. Patients with CAD were randomized to 12 months of combined treatment with atorvastatin and telmisartan [an ARB (angiotensin II receptor blocker)] or atorvastatin and enalapril [an ACEI (angiotensin-converting enzyme inhibitor)]. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 12 months. Levels of miR-146a/b, IRAK1 mRNA, TRAF6 mRNA and TLR4 mRNA/TLR4 protein were significantly higher in the CAD group than in the non-CAD group (all P<0.01). Levels of miR-146a/b were positively correlated with IRAK1 mRNA and TRAF6 mRNA levels. After 12 months of treatment, these levels were markedly decreased in the ARB and ACEI groups, with the decrease in the ARB group being greater than that in the ACEI group (all P<0.05). In our 12-month follow-up study, high levels of miR-146a and TLR4 mRNA/TLR4 protein at baseline were independent predictors of cardiac events. The present study demonstrates that combined treatment with an ARB and a statin decreases miR-146a/b and the TLR4 signal in CAD patients, possibly contributing to the anti-atherogenic effects of ARBs and statins in this disorder.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atorvastatin; Benzimidazoles; Benzoates; Cells, Cultured; Coronary Artery Disease; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Gene Expression Regulation; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; MicroRNAs; Middle Aged; Pyrroles; Renin-Angiotensin System; Signal Transduction; Single-Blind Method; Telmisartan; Toll-Like Receptor 4

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system. Thus, alterations in the renin-angiotensin system by ACE inhibitors probably result in modification of the fibrinolytic system. We examined the effect of a short-term treatment with the ACE inhibitor enalapril in 47 patients with severe coronary artery disease requiring coronary artery bypass grafting (CABG).. Patients received either 20 mg/d enalapril or placebo for 6 days. Tissue-type plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), plasmin-a2-antiplasmin-complex (PAP) and D-dimers were measured initially and after treatment.. In the enalapril group PAI-1 levels were significantly reduced after treatment (11.9 +/- 2.3 U/ml vs. 17.1 +/- 3.0 U/l; P < 0.05). In the placebo group PAP levels were significantly higher ( P < 0.05) after treatment compared to initial values. No differences could be detected between the study groups with regard to TPA and D-dimers.. Although PAI-1 activity levels are reduced after short-term treatment with ACE inhibitors in patients with stable angina pectoris while TPA antigen is unaffected, treatment with ACE inhibitors does not lead to a marked change in plasmin activation.

Topics: Adult; Aged; alpha-2-Antiplasmin; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Coronary Artery Bypass; Coronary Artery Disease; Coronary Thrombosis; Double-Blind Method; Enalapril; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Prospective Studies; Renin-Angiotensin System; Severity of Illness Index; Tissue Plasminogen Activator; Treatment Outcome

High-molecular-weight (HMW) adiponectin has important antiatherosclerotic properties.. This study compared circulating HMW adiponectin concentrations and other parameters between patients with coronary artery disease (CAD) and participants without CAD. We investigated whether treatment with statins and either telmisartan or enalapril might affect HMW adiponectin and other parameters in patients with CAD. Finally, adiponectin concentrations were compared after 6 months of treatment between CAD patients with versus without cardiac events.. Consecutive patients with stable CAD admitted to our hospital (Iwate Medical University School of Medicine, Iwate, Japan) for percutaneous coronary intervention (PCI) and stent implantation and with no previous treatment with renin-angiotensin system blockers or statins were recruited. Patients with CAD who met all eligibility criteria were randomly assigned using computer-generated numbers in a 1:1 ratio to receive telmisartan (40 mg/d) or enalapril (5 mg/d) for 6 months. In addition, all patients with CAD were treated with atorvastatin (10 mg/d). The patients without CAD received no treatment with telmisartan, enalapril, or atorvastatin. Plasma concentrations of total and HMW adiponectin were measured using a highly sensitive ELISA system before PCI or drug treatment (ie, baseline) and after 6 months of treatment. In addition, high-sensitivity C-reactive protein (hs-CRP) and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. To evaluate cardiac events, follow-up coronary angiography was performed at least 6 months after PCI.. This study included 70 patients with stable CAD (mean [SD] age, 65.8 [10.9] years; male/female ratio, 55/15) and 25 participants with normal results on coronary angiography (non-CAD) (mean age, 63.5 [11.2] years; male/female ratio, 20/5). Baseline concentrations (mean [SD]) of HMW adiponectin were significantly lower in the CAD group than in the non-CAD group (2.0 [0.3] vs 9.2 [0.5] microg/mL; P < 0.01). The ratio of HMW to total adiponectin was also lower in the CAD group than in the non-CAD group (0.37 [0.02] vs 0.53 [0.02]; P < 0.01). Baseline concentrations of HMW adiponectin were negatively correlated with hs-CRP (r = -0.60) and HOMA-IR (r = -0.30) in patients with CAD. After 6 months of treatment, the telmisartan group showed significantly increased HMW adiponectin concentrations and HMW/total adiponectin ratio (HMW, 3.7 [0.7] vs 2.1 [0.5] microg/mL; P < 0.01 vs baseline; HMW/total, 0.44 [0.02] vs 0.39 [0.02]; P < 0.05 vs baseline), whereas HOMA-IR was significantly decreased (2.86 [1.93] vs 3.39 [1.77]; P < 0.05 vs baseline). HOMA-IR at follow-up was significantly lower in the telmisartan group than in the enalapril group (2.86 [1.93] vs 3.64 [1.45]; P < 0.05). In contrast, treatment with enalapril was not associated with any significant changes in total or HMW adiponectin concentrations, HMW/total adiponectin ratio, or HOMA-IR. Both the telmisartan and the enalapril groups showed significant decreases in hs-CRP after 6 months (P < 0.05 vs baseline). After 6 months of treatment with either telmisartan or enalapril, HMW adiponectin concentrations were 0.7 (0.2) microg/mL with cardiac events versus 3.2 (0.4) microg/mL without (P < 0.05); HMW/total concentrations were 0.25 (0.03) with cardiac events versus 0.43 (0.01) without (P < 0.01). In contrast, hs-CRP concentrations were higher in patients with cardiac events than in those without cardiac events (2.42 [0.52] vs 1.86 [0.45] log10 microg/dL; P < 0.01).. This study found that treatment with telmisartan and statins (but not enalapril and statins) was associated with a significant increase in HMW adiponectin concentrations and a decrease in insulin resistance in these patients with CAD.

Topics: Adiponectin; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Insulin Resistance; Male; Molecular Weight; Prospective Studies; Telmisartan

The prognostic impact of body mass index (BMI) in patients following acute myocardial infarction (AMI) may be altered by neurohormonal blockade.. The impact of neurohormonal blockade on the association between BMI and mortality was examined in 5548 patients following AMI (CONSENSUS II), 50% receiving enalapril and 7% beta-blockade, and in 4367 patients with coronary artery disease (CAD) (4S), 79% with prior AMI, 12% receiving ACEi and 67% beta-blockade. Median follow-up was 0.4 and 5.2 years, respectively. Patients were categorized into 4 BMI groups: Underweight, < 22.00; normal-weight, 22.00-24.99; overweight, 25.00-29.99; obese, > or = 30.00 kg/m2. Multivariable analysis adjusted for demographics, patient history, physical examination, biochemistry and medication.. CONSENSUS II: Overall, adjusted mortality (n=301) risk was similar across BMI groups. Comparing overweight with normal-weight patients, the hazard ratios (HRs) for mortality differed significantly (P=0.028) between patients randomized to placebo (HR 1.41) and enalapril (HR 0.75). 4S: Overall, adjusted mortality (n=421) risk was similar for normal-weight, overweight and obese patients. In a time-dependent analysis for drug use, comparing obese with normal-weight patients, the HRs for mortality differed significantly (P=0.047) between patients without (HR 1.86) and those with (HR 0.97) neurohormonal blockade.. In patients after AMI or with CAD, high BMI was associated with increased mortality risk among patients not receiving neurohormonal blockade, but with decreased or neutral mortality risk among those receiving neurohormonal blockade. Tests for interaction indicate that neurohormonal blockade may attenuate the relationship between high BMI and increased mortality risk. Neurohormonal blockade may thus partly explain the so-called obesity paradox.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Body Mass Index; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Obesity; Prognosis; Proportional Hazards Models; Risk Factors

In the era of early reperfusion therapy, life-threatening ventricular arrhythmias (VA) remain common after recanalization of an occluded coronary artery. Experimental studies reported that angiotensin-converting (ACE) inhibitors suppress reperfusion-induced VA. However, whether ACE inhibitors lower the incidence of reperfusion clinical VA is unknown. We examined the effects of low doses of intracoronary (i.c.) enalaprilat (EN) as an adjunct to direct percutaneous coronary interventions (PCI) on reperfusion VA in the acute phase of myocardial infarction (MI).. We randomly assigned 22 patients with a first acute MI, who underwent successful direct PCI, to EN, 50 mug, i.c., or placebo (PL), administered immediately after reperfusion. VA were manually edited and counted from 24-hour Holter recordings begun upon hospital admission.. There were no significant between-groups differences in clinical characteristics. Mean RR interval before and after PCI, and the incidence of VA before PCI were similar in both groups. After PCI the incidence of reperfusion-induced VA was significantly lower in the EN-treated group (VPB/h: PL 29.9 +/- 12 vs EN 43.2 +/- 42, P < 0.05; couplets/h: EN 0.9 +/- 0.7 vs PL 4.1 +/- 5.0, P < 0.01; triplets/h: EN 0.3 +/- 0.2 vs PL 1.2 +/- 1.5, P < 0.05; ventricular tachycardia/h: EN 0.3 +/- 0.1 vs PL 0.8 +/- 0.5, P < 0.01).. Compared with PL, i.c. EN significantly lowered the incidence of reperfusion-associated VA. This previously unrecognized antiarrhythmic effect might be an important therapeutic benefit conferred by ACE inhibitors, beyond limitation of infarct size.

Topics: Aged; Angioplasty, Balloon, Coronary; Antihypertensive Agents; Arrhythmias, Cardiac; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Prospective Studies

On-pump coronary artery bypass graft (CABG) surgery triggers an inflammatory response (IR) which may impair revascularization. The study aimed at (1) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood, and (2) determining whether (and which doses of) cardiovascular drugs known to have antiinflammatory properties, namely statins and ACE-inhibitors (ACEI), inhibit the response.. Patients scheduled for CABG (n=22) were randomized to statin/ACEI combination treatment at standard doses (STD, ramipril 2.5/simvastatin 20 mg, or atorvastatin 10 mg), or at high doses (HiDo, ramipril 10 mg, or enalapril 20 mg/simvastatin 80 mg, or atorvastatin 40 mg). Plasma levels of interleukin 6, tumor necrosis factor alpha, E-selectin, von Willebrand factor (vWF), and sVCAM-1 were serially assayed (ELISA) before, during, and after CABG. Blood was drawn from an artery, a systemic vein, and the coronary sinus. Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects. In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping. Such increases were drastically attenuated in the HiDo group. Instead, only modest increases in venous E-selectin, vWF, and sVCAM-1 were observed. Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group.. On-pump CABG surgery is associated with an intense systemic inflammatory response, which can be almost completely prevented by early treatment with high (but not standard) doses of ACE-inhibitors and statins.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Atorvastatin; Coronary Artery Bypass; Coronary Artery Disease; Coronary Circulation; Creatine Kinase; Dose-Response Relationship, Drug; E-Selectin; Enalapril; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Inflammation Mediators; Interleukin-6; Leukocyte Count; Male; Middle Aged; Platelet Count; Pyrroles; Ramipril; Simvastatin; Stroke Volume; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

To investigate the effect of enalapril, losartan, and surgical coronary revascularisation on endothelial function, and the role of the angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism.. Randomised, controlled, blinded end point study.. University tertiary referral cardiac centre.. 49 men awaiting coronary artery bypass grafting (CABG) were randomly assigned to treatment with losartan, enalapril, or control for two months before and three months after surgery.. Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined.. FMD was impaired at baseline (1.0-1.7%) and after five months had improved to 5.2% with enalapril (p = 0.015), 5.0% with losartan (p = 0.0004), and 3.0% with CABG alone (p = 0.05). Patients with the II genotype had lower baseline FMD than those with DI or DD (0.1% v 1.7%, p = 0.038) and after enalapril or losartan treatment had greater improvement in FMD (mean (SEM) 7.1 (1.1)%) than patients with DI (3.1 (1.3)%, p = 0.024) or DD genotype (3.1 (1.1)%, p = 0.02).. Enalapril and losartan, with surgical coronary revascularisation, significantly improve systemic endothelial function. Revascularisation alone produces a quantitatively smaller, but still significant, improvement. The ACE genotype significantly modulates this response. Patients with the II genotype have a more pronounced impairment in endothelial function at baseline and a greater improvement in response to treatment with these agents.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Double-Blind Method; Enalapril; Endothelium, Vascular; Genotype; Humans; Losartan; Male; Middle Aged; Mutation; Myocardial Infarction; Myocardial Revascularization; Risk Assessment; Risk Factors

We evaluated whether renin-angiotensin system (RAS) blockade attenuates cardiovascular events.. Because inflammation and enhanced thrombogenesis are hallmarks of atherosclerosis, we assessed whether RAS inhibition elicits anti-inflammatory and anti-aggregatory effects.. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), metalloprotease 9 (MMP-9), and interleukin 10 (IL-10) were determined in patients with coronary artery disease (CAD) and arterial hypertension six to eight weeks after coronary angioplasty (low-density lipoprotein serum levels <150 mg/dl). Patients were randomized double-blind to either 20 mg enalapril (ENAL, n = 27) or 300 mg irbesartan (IRB, n = 21) for 3 months. Blood samples were drawn at baseline and at three months. Thromboxane A2-induced platelet aggregation was determined turbidimetrically; urine bicyclo-prostaglandin E2 (PGE(2)) and inflammatory markers were measured by enzyme-linked immunosorbent assay technique.. Both treatment regimens enhanced serum IL-10 levels (IRB p < 0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p < 0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05). Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL). Platelet aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p < 0.001) while urine PGE(2) levels remained unchanged.. Angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) blockade reduced serum MMP-9 protein/activity to a similar extent, and only AT1 blockade reduced hsCRP, IL-6, and platelet aggregation in patients with CAD. Thus, AT1-blockade appears to exert stronger systemic anti-inflammatory and anti-aggregatory effects compared with ACE inhibition.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Biphenyl Compounds; C-Reactive Protein; Coronary Artery Disease; Dinoprostone; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Inflammation; Interleukin-10; Interleukin-6; Irbesartan; Male; Matrix Metalloproteinase 9; Middle Aged; Platelet Aggregation; Tetrazoles; Thromboxane A2

The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain.. To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD.. Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS).. Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion.. The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume.. Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07.. Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Ultrasonography, Interventional

This study examined the effects of long term cholesterol lowering therapy with simvastatin on progression and regression of coronary atherosclerosis, as determined by quantitative angiographic end points, in subgroups of patients with known coronary risk factors. In this randomized, placebo controlled clinical trial, the effect of simvastatin on coronary atherosclerosis was compared with that of placebo in 394 patients who had paired coronary angiograms taken an average of four years apart. The effects of treatment on the following prespecified subgroups were examined: sex, age (less than 65 years versus at least 65 years), smoking status (current or previous/never), history of diabetes mellitus or hypertension, and severity of coronary artery lesions (diameter at least 50% versus less than 50%). There were significantly smaller decreases in the average minimum diameters, between closeout and baseline angiograms, in all simvastatin-treated subgroups, compared with placebo. Trends toward or significantly smaller decreases in the average of the mean diameters, and similar smaller increases in percentage diameter stenosis were also seen in all subgroups. The slowing of angiographically demonstrable coronary atherosclerotic narrowing supports the contention that this treatment effect is causally related to the reduction of coronary events repeatedly seen in large outcome clinical trials of lipid lowering therapy. Also, this treatment effect occurs in the presence or absence of the traditional coronary risk factors.

Topics: Aged; Alberta; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Quebec; Severity of Illness Index; Simvastatin; Treatment Outcome; Triglycerides

Topics: Adult; Aged; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; von Willebrand Factor

This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients.. There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients.. This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Blood Pressure; Cholesterol; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Humans; Lipid Metabolism; Male; Middle Aged; Peptidyl-Dipeptidase A; Simvastatin; Treatment Outcome

In the treatment of coronary atherosclerotic artery disease (CAD), the mechanisms by which lipid lowering, a proven therapy, produces beneficial clinical effects remain unclear. Moreover, although potential mechanisms of benefit are well known and increasingly applied clinically, there are no conclusive data from clinical trials studying primarily the antiischemic effects of angiotensin-converting enzyme (ACE) inhibition in patients with normal heart function. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) is designed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol. DESIGN AND OBJECTIVES: SCAT is a three- to five-year, multicentre, randomized, double-blind, placebo controlled, 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and/or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L.. Of 460 patients (age 61 +/- 9 years; 409 males, 51 females) enrolled between June 1991 and July 1995, 230 were randomized to simvastatin and 230 to placebo, and 229 to enalapril and 231 to placebo. Average baseline total cholesterol level was 5.20 +/- 0.61 mmol/L, high density lipoprotein cholesterol was 0.99 +/- 0.25 mmol/L, low density lipoprotein cholesterol was 3.36 +/- 0.57 mmol/L and triglycerides were 1.82 +/- 0.75 mmol/L. The trial will be completed in June 1998.. Insights gained from this long term angiographic trial will lead to a better understanding of the mechanisms of benefits of these two treatments, both alone and in combination. Of particular interest is that this trial will be able to examine a suspected beneficial interaction, if present, between these two treatments.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anticholesteremic Agents; Cholesterol; Coronary Angiography; Coronary Artery Disease; Disease Progression; Double-Blind Method; Enalapril; Female; Humans; Lovastatin; Male; Middle Aged; Research Design; Simvastatin; Treatment Outcome; Ventricular Function, Left

In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Follow-Up Studies; Humans; Leukocyte Count; Male; Middle Aged; Myocardial Infarction; Pancreatic Elastase; Peptide Fragments; Platelet Activation; Platelet Aggregation; Risk Factors; Survival Rate

This post hoc analysis of CAMELOT and PREVENT analyzed the impact of blood pressure variability (BPV, assessed as within-subject standard deviation of SBP from 12 weeks onward) on the incidence of major adverse cardiovascular events (MACE, defined according to original studies). Patients (n = 1677 CAMELOT; n = 776 PREVENT) were stratified by BPV quartile. Regardless of study, BPV was significantly lower for amlodipine versus other treatments. In CAMELOT, a significant association between BPV quartile and MACE was observed with amlodipine treatment. Significant associations between BPV quartile and MACE were observed for both studies, when analyzed overall (adjusting for treatment). In CAMELOT, with amlodipine treatment, an increased risk for MACE was observed with high (BPV ≥ Q3) versus low BPV (< Q1; adjusting for characteristics and risk factors). In both studies, increased risk for MACE was observed for BPV ≥ Q3 versus BPV < Q1 (analyzed overall, adjusting for treatment and covariates). For both studies, BPV, but not mean SBP, was associated with cardiovascular events. BPV was associated with cardiovascular outcomes in patients with CAD and well-controlled BP.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Coronary Artery Disease; Enalapril; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

Coronary heart disease (CHD) is the number one cause of death in the US. The adipokine adiponectin has been studied intensively for presenting and inversed association with almost every stage of CHD. For instance, the evaluation of molecules capable of enhancing endogenous adiponectin expression is well justified. In this study, we investigated the effect of the vitamin D receptor activator (VDRA) paricalcitol and the angiotensin-converting enzyme inhibitor (ACEI) enalapril on adiponectin expression, lipid profiles, adenosine monophosphate activated protein kinase (AMPK) expression, monocyte chemo-attractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFα),cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), antioxidant capacity, CuZn-superoxide dismutase (CuZn-SOD), Mn-SOD, NADPH p22phox subunits, inducible nitric oxidesynthase (iNOS), endothelial marker eNOS, and 81 atherosclerosis-related genes in ApoE-deficient mice.. Seven-week-old ApoE-deficient mice were treated for 16 weeks as follows: Group 1, ApoE vehicle control (intraperitoneal [i.p.] 100 µl propylene glycol); Group 2, ApoE-paricalcitol (200 ng i.p., 3/week); Group 3, ApoE-Enalapril (30 mg/kg daily); Group 4, ApoE-paricalcitol + enalapril (described dosing); and Group 5, wild-type control (C57BLV).. All treated groups presented significant changes in circulating and cardiac adiponectin, cardiac cholesterol levels, AMPK, MCP-1, TNF-α, COX-2, iNOS, eNOS, CuZn-SOD, Mn-SOD and p22phox. There were 15 genes that differed in their expression, 5 of which are involved in cardioprotection and antithrombotic mechanisms: Bcl2a1a, Col3a1, Spp1 (upregulated), Itga2, and Vwf (downregulated).. Together, our data presented a novel role for VDRA and ACEI in reducing factors associated with CHD that may lead to the discovery of new therapeutic venues.

Topics: Adiponectin; Angiotensin-Converting Enzyme Inhibitors; Animals; Apolipoproteins E; Blotting, Western; Coronary Artery Disease; Disease Models, Animal; Drug Therapy, Combination; Enalapril; Ergocalciferols; Female; Gene Expression Regulation; Mice; Mice, Inbred C57BL; Oxidative Stress; Polymerase Chain Reaction; Receptors, Calcitriol; RNA

Effects of combined drug therapy were evaluated in 97 patients during a year Group 1 comprised 32 patients with chronic obstructive pulmonary disease (COPD), group 2 (n = 34) included patients with COPD and angina of effort, group 3 (n = 31) patients with CHD. Broncholytic therapy was prescribed in compliance with GOLD (2006) recommendations. Patients in groups 2 and 3 continued to receive antianginal therapy started before the onset of the study. Combined therapy included ACE inhibitor enalapril. Positive effect of inpatient treatment of COPD on lung function was transient and subsided with time. Specifically, forced expiratory volume in the 1st second and forced pulmonary vital capacity decreased below the acceptable physiological bounds. BODE index tended to drop too because exercise tolerance increased while dyspnea index by MMRC decreased despite impaired FEV1 and tendency toward a fall in BMI. Echocardiography revealed diminished size of both ventricles and improved left ventricular systolic function. However, heart remodeling progressed with time. Adequate therapy resulted in the reduction of CHD functional class and produced positive antianginal, antihypertensive, and antiarrhythmic effects. The treatment was well tolerated by the patients. It is concluded that combined therapy of COPD including enalapril improves respiratory symptoms and decreases manifestations of concomitant pathology.

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Bronchodilator Agents; Coronary Artery Disease; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Vasodilator Agents

Increasing evidence suggests that angiotensin converting enzyme (ACE) inhibitors exert antithrombotic effects. Based on the assumption of differential effects of various ACE inhibitors on coagulation, the aim of the present study was to evaluate the coagulative activities of cardiovascular (CV) patients treated with either ramipril, captopril, and enalapril, and to compare these with patients treated with established antithrombotics such as aspirin (ASA) and clopidogrel or none of these medication.. Blood samples of 320 CV patients with coronary artery disease and/or arterial hypertension were analyzed by wholeblood aggregometry. Platelet aggregation was determined by measuring the increase in impedance across paired electrodes in response to the aggregatory agents collagen and adenosine diphosphate (ADP), respectively. These data were correlated with medical treatment.. Platelet aggregation was attenuated ex vivo by ramipril and captopril as well as by ASA and clopidogrel. While collagen-induced platelet aggregation was significantly reduced by ramipril (35%; P <0.01) and captopril (27%; P = 0.01), no change was seen with enalapril. After induction with ADP, platelet aggregation was reduced in the presence of captopril therapy by 46% (P <0.05). There was a trend of inhibition with ramipril (32%, P = n.s.), whereas no antithrombotic effect was seen with enalapril.. Our findings demonstrate that ACE inhibitors decrease platelet aggregation ex vivo. The differential antiaggregatory profile may explain at least in part different effects of ACE inhibitors on cardiovascular endpoints as observed in large clinical trials.

Topics: Adenosine Diphosphate; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Captopril; Cardiovascular Diseases; Clopidogrel; Collagen; Coronary Artery Disease; Electric Impedance; Enalapril; Female; Fibrinolytic Agents; Germany; Humans; Hypertension; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Ramipril; Ticlopidine; Treatment Outcome

In patients with coronary artery disease (CAD), therapies designed to prevent clinical events are not always associated with significant reduction in coronary obstruction, as measured by quantitative coronary angiography. We set out to explore the relationship between quantitative coronary angiography parameters, baseline characteristics, and clinical events in a large trial of CAD regression with antihypertensive agents.. Patients randomized to amlodipine, enalapril, or placebo in the CAMELOT trial were followed for 24 months for major ischemic events. Among 431 patients participating in the angiographic and intravascular ultrasound substudy NORMALISE, 298 (99 amlodipine, 96 enalapril, and 103 placebo) had complete angiographic and intravascular ultrasound data. The patients did not differ significantly with respect to baseline characteristics (except for diabetes) or extent of CAD. After 24 months, the change in minimal lumen diameter (MLD) was -0.02 +/- 0.13 for amlodipine, -0.03 +/- 0.12 for enalapril, and -0.03 +/- 0.17 mm for placebo (P = .40). Major ischemic events occurred in 20.2%, 24%, and 25.2%, respectively (P = .68). There was no significant correlation between change in MLD and age, sex, statin therapy, or systolic blood pressure at baseline. The change in MLD did not differ in patients with and without cardiovascular events, regardless of treatment assignment (P = .54). Only the extent of CAD was independently predictive of ischemic events.. As compared to placebo, amlodipine treatment resulted in fewer ischemic events after 24 months of therapy, but the clinical benefit was not associated with a commensurate improvement in arterial lumen dimensions.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Angiography; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Randomized Controlled Trials as Topic; Thrombosis; Treatment Failure; Ultrasonography, Interventional

Topics: Amlodipine; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Coronary Vasospasm; Enalapril; Humans

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Enalapril; Humans

Concentrations of kininogens, prekallikrein, fibrinogen and antigens of protease inhibitors as well as kininase, fibrinolytic and antipapain activities were estimated in blood plasma (or serum) of patients with coronary artery disease (CAD) before and after the exercise test. The study was conducted on 44 subjects with chronic, stable CAD and 54 myocardial infarction patients (15 treated with streptokinase and 39 subjected to primary percutaneous transluminal coronary angioplasty, PTCA). The patients were divided into two subgroups: treated and untreated with angiotensin I-converting enzyme inhibitor (ACE-I), enalapril. Activation of the fibrinolytic system and the prekallikrein during the exercise test was demonstrated. No significant kininogen consumption was observed. A decrease in kininase activity was found. The results suggest the possibilities of endothelial cells contribution to plasminogen activation in CAD patients. Kininogen and kallikrein directly, or through the released kinins, may participate in regulation of endothelial cell hemostatic functions. Conversion of plasminogen to plasmin may undergo under the influence of kallikrein. The bradykinin induces the tissue plasminogen activator (t-PA) secretion, which depends also on the increased blood flow during the exercise test.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Coronary Artery Disease; Enalapril; Exercise Test; Female; Hemostasis; Humans; Kallikrein-Kinin System; Male; Middle Aged; Myocardial Infarction

Restenosis following percutaneous transluminal coronary angioplasty continues to be a major limitation of the procedure. To test whether an angiotensin-converting enzyme inhibitor may reduce restenosis, this study utilized an atherosclerotic, stented, Hanford miniature swine model of restenosis.. Each animal first was started on an atherogenic diet and had balloon abrasion of the left anterior descending and right coronary arteries. Four months later, balloon-mounted coil stents were placed into the abraded coronary arteries of each animal. Twenty-four animals then were randomly assigned to one of two groups: enalapril, and control. The enalapril group received 50 mg orally twice daily starting 1 week before intracoronary stenting.. Follow-up 2 months later revealed angiographic stenosis in the control group of 30% +/- 13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/- 9%/20% +/- 11% in the enalapril group (P = not significant). The change in minimal lumen diameter from immediately after stenting to follow-up was not significantly different between control and enalapril groups. Area stenosis and maximal intimal thickness obtained by morphometric analysis were also compared, and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/- 16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns. There was no statistical difference.. Enalapril fails to reduce restenosis in this animal model.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Angiography; Coronary Artery Disease; Enalapril; Random Allocation; Recurrence; Swine; Swine, Miniature