ramipril and Coronary-Artery-Disease

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjects enrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associated with a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130-140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.

Topics: Aged; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Hypotension; Male; Middle Aged; Ramipril; Randomized Controlled Trials as Topic; Reference Values; Risk Factors; Stroke; Telmisartan

Angiotensin-convertng enzyme (ACE) inhibitors are well recognized for their benefits in treating hypertension and congestive heart failure and preventing postmyocardial infarction heart failure or left ventricular (LV) dysfunction. Recently, blockade of the angiotensin II type 1 (AT1) receptor was shown to reduce cardiovascular events in hypertensive subjects with LV hypertrophy. Several lines of evidence are now converging to show that ACE inhibitors may affect the atherosclerotic process itself. Emerging clinical data indicate that angiotensin-receptor blockers (ARBs) may possibly modulate atherosclerosis as well. The antiatherogenic properties of ACE inhibitors and ARBs may derive from inhibition or blockade of angiotensin II, now recognized as an agent that increases oxidative stress.Angiotensin-converting enzyme inhibition and angiotensin-receptor blockade also increase endothelial nitric oxide formation, which improves endothelial function. In contrast to the effects of ARBs, the vascular effects of ACE inhibitors may, in part, be mediated by an increase in bradykinin. This article reviews some of the biologic mechanisms whereby ACE inhibitors and ARBs may modulate atherosclerosis.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Coronary Artery Disease; Disease Progression; Endothelium, Vascular; Humans; Ramipril; Renin-Angiotensin System

The goals of rational antihypertensive medication should embrace the alleviation of atherosclerosis, the clinical consequences of which pose a major health problem and hence socio-economic concern for industrialized countries. Angiotensin converting enzyme (ACE) inhibitors are endowed with pharmacodynamic features which may help to attain this aim. Various animal experiments with cholesterol-fed rabbits, pigs and monkeys, as well as with rabbits with inherent disorder of lipid metabolism (WHHL-rabbit), demonstrated endothelial protection against loss of function due to hyperlipidemia and attenuation of lipid deposition in conduit blood vessels with ACE-inhibition. The alleviation of progressive atherosclerosis, which is a common feature of restenosis development following angioplasty, was shown in hypercholesterolemic rabbits and normal rats, but did not occur in clinically more relevant porcine models nor in large clinical trials. Circumstantial evidence from miscellaneous experiments is in line with the view that it is enhancement of bradykinin activity which causes the endothelial protection against the consequences of hypercholesterolemia. Furthermore, loss of relaxation of coronary resistance vessels without overt atherosclerosis despite hypercholesterolemia can be restored by augmentation of the EDRF-pathway as has been demonstrated with ramiprilat in vitro. This is being substantiated in preliminary clinical reports with different ACE-inhibitors. The possible association between improvement in both insulin sensitivity and endothelial function requires further investigation. The critical analysis of present experimental findings on a beneficial influence on both the spontaneous and the progressive development of atherosclerosis indicates ACE-inhibition to be more likely to preserve or restore the function of an intact endothelium than to interfere with the complex reaction occurring after injury of an already affected blood vessel.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Coronary Artery Disease; Coronary Circulation; Disease Models, Animal; Endothelium, Vascular; Haplorhini; Hemodynamics; Rabbits; Ramipril; Rats; Swine; Vascular Resistance

Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by -34/-21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associated with an increased risk of stroke, whereas the risk of MI increased with systolic BP and not with diastolic BP. In conclusion, in patients with coronary artery disease and initially free from congestive heart failure, a BP reduction from baseline over the examined BP range had little effect on the risk of MI and predicted a lower risk of stroke. An increase in systolic BP from baseline increased the risk of stroke and MI. The relationships of BP with risk were much steeper for stroke than for MI. A treatment-induced BP reduction over the explored range seems to be safe in patients with coronary artery disease.. http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Coronary Artery Disease; Diastole; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Ramipril; Stroke; Systole; Telmisartan; Time Factors; Treatment Outcome

Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in vitro and in vivo, resulting in diminished vascular regeneration.

Topics: Adult; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Apolipoproteins E; Apoptosis; Benzimidazoles; Benzoates; Blood Vessels; Bone Marrow Transplantation; Cell Count; Cells, Cultured; Coronary Artery Disease; Double-Blind Method; Endothelial Cells; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Ramipril; Receptor, Angiotensin, Type 1; Regeneration; Stem Cells; Telmisartan; Vasoconstrictor Agents

Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied.. A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo treated patients.. The mean (+/- SD) age was 53+/-9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was --13.2% (95% CI --22.3% to --3.2% ) in the placebo group compared with --21.1% (95% CI --29.9% to --11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial.. A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; C-Reactive Protein; Confidence Intervals; Coronary Artery Disease; Double-Blind Method; Female; Health Status Indicators; Humans; Hypertension; Inflammation; Male; Middle Aged; Ramipril

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

Individual markers of inflammation may add incremental predictive value in the context of conventionally available risk factors. We evaluated the ability of 9 inflammatory biomarkers, microalbuminuria, and N-terminal pro-brain natriuretic peptide (Nt-proBNP) to improve cardiovascular risk prediction beyond that obtained from traditional risk factors in a secondary-prevention population.. We measured biomarkers representing the acute-phase reaction (C-reactive protein, fibrinogen, and interleukin-6), proinflammatory pathways (soluble tumor necrosis factor receptor-1 and -2, soluble interleukin-1 receptor antagonist, and interleukin-18), endothelial activation (soluble vascular adhesion molecule-1 and soluble intercellular adhesion molecule-1), Nt-proBNP, and microalbuminuria in 3199 study individuals of the Heart Outcomes Prevention Evaluation (HOPE) Study and assessed their association with risk of myocardial infarction, stroke, or cardiovascular death (primary outcome, n=501) over 4.5 years of follow-up. In a backward Cox regression procedure that included risk factors and biomarkers, Nt-proBNP (hazard ratio [HR] 1.72 per increment SD, 95% CI 1.39 to 2.12; P<0.0001), soluble intercellular adhesion molecule-1 (HR 1.46, 95% CI 1.19 to 1.80; P=0.0003), microalbuminuria (HR 1.55, 95% CI 1.22 to 1.98; P=0.0004), soluble interleukin-1 receptor antagonist (HR 1.30, 95% CI 1.05 to 1.61; P=0.02), and fibrinogen (HR 1.31, 95% CI 1.05 to 1.62; P=0.02) remained significantly related to the primary outcome. Only inclusion of Nt-proBNP provided incremental information above that obtained by models of traditional risk factors.. Although levels of various inflammatory biomarkers are significantly related to future cardiovascular risk, their incremental predictive value is modest. A model consisting of simple traditional risk factors and Nt-proBNP provided the best clinical prediction in the secondary-prevention population.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Female; Fibrinogen; Heart Diseases; Humans; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Ramipril; Risk Factors; Vitamin E

Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, used alone or in combination, have been shown to improve outcomes in certain populations, primarily when administered in high doses. For stable coronary atherosclerotic disease, however, the relative physiologic effect of these therapies is unclear. Furthermore, because of the notorious subtarget dosing of such agents in clinical practice, we explored the influence of a modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blockers, and the combination on common biologic markers of coronary atherosclerotic disease.. This randomized, cross-over study enrolled stable coronary atherosclerotic disease patients (n=20), each receiving three treatments: candesartan 16 mg daily, ramipril 5 mg daily, and candesartan 8 mg plus ramipril 2.5 mg daily. Treatments were administered for 2 weeks with a 2-week washout. Blood samples were collected before and after each treatment. Markers of endothelial function, fibrinolytic balance, and vascular inflammation were measured.. No significant differences were observed in the pretreatment concentrations of angiotensin-converting enzyme or of any measured biologic marker. Relative to pretreatment levels, candesartan alone was the only therapy to exhibit an action on any measured biomarker--a trend toward increased nitric oxide concentrations (P=0.054). Otherwise, no effects on biologic markers were observed with the treatments.. This study of various methods of the renin-angiotensin system inhibition in stable coronary atherosclerotic disease patients demonstrates negligible effects of a modest dosing of ramipril and the combination of ramipril plus candesartan on common biologic markers of coronary atherosclerotic disease. Candesartan at modest doses may favorably influence endothelial function. Overall, however, the results indicate that the commonly practiced subtarget dosing of such treatments provides little, if any, benefit pertaining to key physiologic components of coronary atherosclerotic disease.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biomarkers; Biphenyl Compounds; Coronary Artery Disease; Cross-Over Studies; Drug Therapy, Combination; Endothelium, Vascular; Female; Fibrinolysis; Humans; Inflammation; Male; Middle Aged; Ramipril; Tetrazoles

Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis.. A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l).. The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Blood Pressure; Cholesterol, LDL; Coronary Artery Disease; Coronary Disease; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Male; Middle Aged; Premedication; Prospective Studies; Ramipril; Treatment Outcome

Because the mechanisms of the biological effects of statin and angiotensin converting enzyme inhibitor therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic patients with coronary artery disease. We administered simvastatin 20 mg and placebo or ramipril 10 mg daily during 2 months with washout 2 months to 32 hypercholesterolemic patients with coronary artery disease. This study was randomized, double-blind, placebo-controlled, crossover in design. Simvastatin alone or combined with ramipril significantly changed lipoproteins, and improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements by 33 +/- 6% and by 50 +/- 14%, respectively (both P <0.001) and reduced plasma levels of nitrate relative to baseline measurements (P=0.413 and 0.037, respectively), the plasma MDA levels relative to baseline measurements by 8 +/- 8% and by 18 +/- 9% (P=0.039 and P <0.001, respectively) and MCP-1 relative to baseline measurements by 7 +/- 4% and by 13 +/- 3%, respectively (P=0.019 and P <0.001, respectively), and CRP from 0.22 to 0.14 mg/dl and from 0.22 to 0.15 mg/dl, respectively (P=0.124 and 0.002, respectively), and PAI-1 antigen relative to baseline measurements (P=0.690 and 0.018, respectively). However, simvastatin combined with ramipril changed to greater but statistically insignificant extent the percent flow-mediated dilator response to hyperemia and plasma levels of nitrate, MDA, MCP-1, and PAI-1 antigen than simvastatin alone. Simvastatin alone or combined with ramipril showed significant beneficial effects on endothelial function in hypercholesterolemic patients with coronary artery disease. However, simvastatin combined with ramipril did not significantly change, compared with simvastatin alone.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Ramipril; Simvastatin; Vasomotor System

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Carotid Artery Diseases; Coronary Artery Disease; Disease Progression; Double-Blind Method; Female; Humans; Intracranial Arteriosclerosis; Male; Ramipril; Research Design; Risk Factors; Ultrasonography; Vitamin E

Unlike most cell-types in the body, cardiomyocytes do not replicate in adult life. Consequently myocardial infarction produces irreparable damage to the heart which in turn increases the likelihood of premature death. Recent trials indicate that immediate aspirin and thrombolytic therapy beneficially modify the natural history of myocardial infarction, reducing both short- and long-term mortality rates. However, the occurrence of early heart failure in as many as one third of patients continues to carry with it a particularly poor prognosis. Recent trials with ACE inhibitors indicate that delayed initiation (beyond 24 h) and long-term maintenance treatment of patients selected on the basis of either heart failure (AIRE Study) or an ejection fraction of less than 40% (SAVE Study) result in large reductions in all-cause mortality. Although the exact mechanism of this benefit remains uncertain the reduction of further myocyte death due to reinfarction or gradual toxic attrition has been suggested. The currently unreported ISIS-4 and GISSI-3 should provide additional information as to whether the clinical indications for ACE-inhibitor therapy should be extended to other patient groups.

Topics: Coronary Artery Disease; Heart Failure; Humans; Myocardial Infarction; Ramipril; Recurrence; Risk Factors; Stroke Volume; Survival Analysis; Ventricular Function, Left

Topics: Benzimidazoles; Benzoates; Blood Pressure; Coronary Artery Disease; Female; Humans; Male; Myocardial Infarction; Ramipril; Stroke; Telmisartan

Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in patients with diabetes. Individuals with prediabetes states, with or without known CHD, should undergo lifestyle modifications aimed at preventing DM. In patients with CHD and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor, along with strict glycemic, blood pressure, and lipid control, is strongly recommended. Intense insulin therapy may be needed for glycemic control, and high-dose statin therapy may be needed for lipid control. For blood pressure control, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are considered first-line therapy. Noncompliance with medications and/or lifestyle measures and underprescription of evidence-based therapies remain important unsolved problems.

Topics: Antihypertensive Agents; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus; Diabetic Angiopathies; Humans; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Life Style; Myocardial Infarction; Obesity; Pioglitazone; Piperidines; Platelet Aggregation Inhibitors; Prediabetic State; Pyrazoles; Ramipril; Rimonabant; Risk Assessment; Thiazolidinediones; Triglycerides; Weight Loss

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

Cumulative evidence supports the use of angiotensin-converting enzyme (ACE) inhibitors for stable coronary artery disease in patients with and without heart failure. The dose and unique properties of ACE inhibitors, trial data, differences in trial design and demographics, may all contribute to variable responses in clinical outcomes. Pending direct comparator clinical trials between a tissue ACE inhibitor vs a plasma ACE inhibitor, evidence indicates that both ramipril and perindopril can be recommended for secondary risk prevention.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Humans; Middle Aged; Perindopril; Ramipril; Randomized Controlled Trials as Topic; Treatment Outcome

Although atherosclerosis is today seen as presenting a distinct clinical picture, there are almost no data available about the impact this has on medical practice and about the point at which a patient is considered high-risk. As part of a larger project on the prevention of heart disease and atherosclerosis, "Aktion plus leben", 1,117 physicians were polled in a scientific survey. The study was carried out in some 100 hospitals throughout Austria, above all in departments of internal medicine, but also in neurological departments, and in a number of other units. The results showed that in fact over 90% of those questioned see atherosclerosis as a separate, treatable illness in the context of risk prevention. The most frequent methods of diagnosis were specified as ultrasound and the clarification of symptoms of coronary heart disease. Atherosclerosis prevention is initiated above all in patients with coronary heart disease, myocardial infarction and stroke, but also very frequently in those with diabetes, peripheral vascular occlusive disease, hyperlipidemia and hypertension. Of particular interest to us was the respondents' evaluation of the effect of ramipril, the angiotensin-converting enzyme (ACE) inhibitor used in the HOPE study. The majority of those questioned see a broad range of indications for this ACE inhibitor and ascribe to it a profibrinolytic, antiinflammatory and plaque-stabilising action. Although the survey sought assessment of just one particular medication as a possible treatment option, the study documents the importance of a more inclusive concept of atherosclerosis prevention.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Attitude of Health Personnel; Austria; Clinical Trials as Topic; Coronary Artery Disease; Health Promotion; Humans; Ramipril; Risk Factors; Treatment Outcome

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Coronary Artery Disease; Coronary Vessels; Drug Therapy, Combination; Humans; Ramipril; Randomized Controlled Trials as Topic; Telmisartan