Quinapril ischemic event trial.
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Angiotensin-Converting Enzyme Inhibitors↗
Biomedical subjects
G B Mancini
Publications and source records attributed to G B Mancini.
Angiotensin converting enzyme inhibitors and restenosis: let's stop teasing ourselves.
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Angiotensin-Converting Enzyme Inhibitors↗
Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA).
BACKGROUND: The Total Occlusion Study of Canada (TOSCA) is a multicenter, randomized trial evaluating the effect of stenting with > =1 heparin-coated stent on long-term patency after percutaneous coronary intervention by balloon angioplasty of occluded coronary arteries. The purpose of the current study was to compare the effect of stenting and balloon angioplasty on global left ventricular ejection fraction (LVEF) and regional wall motion and to examine what clinical and angiographic factors may have an effect on left ventricular function in this setting. METHODS AND RESULTS: Analysis at the core angiographic laboratory of paired baseline and follow-up left ventricular angiograms, as well as target vessel patency, was possible in 244 of 410 cases. An improvement in LVEF was observed in the entire group (59.4% +/- 11% to 61.0% +/- 11%, P =.003). The LVEF change was +1.84 +/- 7.54 in the stent group (P =.009) and 1.28 +/- 8.16 in the percutaneous transluminal coronary angioplasty group (P =.085). There was no significant intergroup difference. Patients with duration of occlusion < or =6 weeks had an improvement in LVEF (+2.98 +/- 8.68, P =.0006), whereas those with an occlusion duration of > 6 weeks had no improvement (+0.48 +/- 7.01, P not significant). Multivariate analysis revealed baseline LVEF <60%, duration of occlusion < or =6 weeks, and Canadian Cardiology Society angina class I or II to be independent predictors of improvement in LVEF. CONCLUSIONS: The restoration of coronary patency of nonacute occluded coronary arteries is associated with a small but significant improvement in regional and global left ventricular function, especially in patients with recent occlusions and depressed left ventricular function. In spite of significant effect on long-term patency, stenting of nonacute coronary occlusions does not result in significantly better left ventricular function compared with balloon angioplasty in this setting.
Angioplasty, Balloon, Coronary↗
Why were the results of the Heart Outcomes Prevention Evaluation (HOPE) trial so astounding?
The Heart Outcomes Prevention Evaluation (HOPE) study was important because it showed the benefits of ramipril - an angiotensin-converting enzyme (ACE) inhibitor - in patients at high risk for cardiovascular events. Treatment with ramipril significantly reduced the rates of death, myocardial infarction, stroke, coronary revascularization, cardiac arrest and heart failure, as well as the risk of diabetes-related complications and of diabetes itself. The effects of therapy with vitamin E were also evaluated, but no statistical benefits were shown. The benefits of ACE inhibitor therapy that were observed were likely due to a variety of mechanisms, not just a reduction in blood pressure.
Angiotensin-Converting Enzyme Inhibitors↗
A comparison of quantitative coronary angiography systems using a unique set of in vivo coronary stenosis images.
OBJECTIVE: To compare the accuracy and precision of measurements of minimum lumen diameter (MLD) among two existing, and one new, quantitative coronary angiography systems. MATERIALS AND METHODS: The analysis was performed using in vivo cinearteriograms of precisely drilled, radiolucent plastic beads that were inserted percutaneously into the coronary arteries of canines. The existing algorithms compared were the ArTrek and the Coronary Measurement System (CMS). The latter was applied in two modes: a mode based on a minimal cost analysis algorithm and a mode based on a gradient field transform. The new algorithm (CorTrek) was also applied in two modes: a mode called the ArTrek compatible mode and a mode known as the 'regression' mode. The latter mode uses a look-up table, based on a phantom calibration step, to readjust the measured MLD to overcome system nonlinearities (overestimation of small diameters and underestimation of large diameters). RESULTS: In the absence of editing, the optimal accuracy (no significant bias) was achieved with the ArTrek compatible algorithm (-0.03 mm for an MLD between 0.83 and 1.83 mm). All other algorithms showed significant under- or overestimation of the MLD within this range. The precision ranged from 0.18 to 0.40 mm without editing, and was best with the ArTrek algorithm. CONCLUSIONS: The present study provides in vivo validation and comparative performance characteristics of a new, accurate coronary quantitative angiography system.
Algorithms↗
Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators.
BACKGROUND: The results of angiographic studies have suggested that calcium channel-blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. METHODS AND RESULTS: The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (P:=0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0. 0126-mm decrease in the amlodipine group (P:=0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. CONCLUSIONS: Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.
Aged↗
Temporal response of brachial artery dilation after occlusion and nitroglycerin.
This study shows that a set time after cuff deflation or after nitroglycerin administration may not be suitable to capture peak, brachial artery dilatory responses in assessing endothelial dysfunction. Automated, continuous monitoring methods are required to simplify identification of peak responses and to standardize reporting.
Administration, Sublingual↗
Carotid intima-media thickness as a measure of vascular target organ damage.
This paper summarizes important investigations published within the past 2 years that use B-mode carotid ultrasound and measurements of intima-media thickness or plaque to elucidate the relationship between traditional or novel risk factors for the development of atherosclerotic or arteriosclerotic disease. This methodology is proposed as an extremely useful, noninvasive tool with proven ability to show cross-sectional associations with cardiovascular risk factors, prevalence of vascular disease, and predictive power. The method appears highly suited to the goal of detecting asymptomatic vascular target organ damage, which may greatly assist with assessment of risk and selection of appropriate, preventive, strategies for management of disease.
Aged↗
Pharmacotherapy of hypercholesterolaemia: statins in clinical practice.
The objective of this article is to evaluate the roles of the lipid-lowering class of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in reducing cardiovascular events and to review their mechanism of action based on in vitro and in vivo studies. The clinical outcome of 15 major clinical trials has been critically reviewed and summarised; all showed a high degree of efficacy and safety. Statins, either in active or prodrug forms, are potent inhibitors of HMG-CoA reductase, have good absorption rate and their bioavailability depends on their lipophobicity and concomitant use with meals. Abdominal discomfort is the most commonly reported adverse effect. Although the incidence is low, myopathy with or without rhabdomyolysis may be considered a serious adverse effect of statins. A combination of a statin with gemfibrozil seems to increase the risk of this adverse event, particularly in patients with renal impairment. Combination therapy with several other agents, frequently administered to cardiovascular patients, has also been reviewed. Statin therapy is considered highly cost effective in secondary prevention, but it is less cost effective in primary prevention. This factor may underline the rationale for developing other safe and effective agents with an improved cost effectiveness profile. The pleiotropic non-lipid lowering effects of statins may include their anti-oxidant and antithrombotic potential as well as restoration of endothelial function. Statins may also be beneficial in the treatment of osteoporosis. Fewer studies have investigated statins' effects on the quality of lipoprotein particles, the activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase as well as their possible synergistic effects with n-3 fatty acids, anti-oxidants and aspirin in reducing cardiovascular events.
Anticholesteremic Agents↗
Long-term use of angiotensin-converting enzyme inhibitors to modify endothelial dysfunction: a review of clinical investigations.
OBJECTIVES: Endothelial dysfunction can be modified by angiotensin-converting enzyme (ACE) inhibitors. The purpose of this paper is to review clinical studies assessing the effect of long-term, oral ACE inhibition on endothelial dysfunction in specific disease syndromes and to identify areas requiring further research. DATA SOURCES: A computer search of the entire MEDLINE database and Current Contents complemented by detailed analysis of references in the papers identified. STUDY SELECTION: Analysis of patients treated on a long-term basis with orally administered ACE inhibitors to modify endothelial function. DATA SYNTHESIS: Studies were identified of patients with hypertension, diabetes, congestive heart failure, coronary artery disease, dyslipidemias and immunoglobulin A nephropathy (IgAN). These studies used diverse endothelium-mediated end-points, which included dilatory responses in conduit or resistance vessels, measures of coagulant and fibrinolytic factors, soluble adhesion molecules, endothelin-1, systemic and glomerular barrier functions and renal blood flow. Few trials enrolled large numbers of patients or used randomized, double-blind, placebo-controlled designs. However, consistent and positive effects were noted in patients with coronary artery disease, dyslipidemia or IgAN. In hypertensive patients, conduit artery and renal endothelium-mediated responses could be improved earlier and more easily than resistance vessel function, which appears to require prolonged therapy before improvement is seen. Highly disparate results were found in patients with congestive heart failure or diabetes. CONCLUSIONS: ACE inhibitors appear to improve endothelial dysfunction in patients with coronary artery disease, dyslipidemia, hypertension and IgAN. Conflicting evidence exists in studies of patients with congestive heart failure and diabetes. Further trials are required to clarify and define the prevalence of endothelial dysfunction and the predictors of response in all these conditions.
Angiotensin-Converting Enzyme Inhibitors↗
The rationale for long-term prophylaxis of venous thromboembolism.
Prophylaxis for venous thromboembolism (VTE) after surgery has traditionally been given from the time of surgery until hospital discharge, typically ranging from 5-14 days. Recently, there has been a trend toward shorter periods of hospitalization. Furthermore, a number of prospective studies have demonstrated that a significant proportion of patients develop deep vein thrombosis (DVT) or pulmonary embolism (PE) up to 5 or 6 weeks following general or orthopedic surgery. Therefore, prolonged prophylaxis during the post-discharge period may provide clinical benefits in high-risk patients. However, the optimal duration of prophylaxis for VTE after surgery remains unclear. In elective hip replacement, four studies of prolonged prophylaxis with low-molecular-weight heparin (LMWH) for 3- 4 weeks after hospital discharge demonstrated a significant reduction in the incidence of venography-confirmed DVT. These results support the use of prolonged thromboprophylaxis in the outpatient setting. Effective outpatient prophylaxis must be safe and convenient for patients to maximize compliance and clinical benefits. Low-molecular-weight heparins are safe and effective when given at a fixed daily dose, and pharmacoeconomic studies suggest that prolonged prophylaxis with these agents may be cost-effective. Key challenges for the future include identifying the patients who require prolonged prophylaxis and determining the duration of treatment.
Anticoagulants↗
Overview of the prospective randomized evaluation of the vascular effects of Norvasc (amlodipine) trial: PREVENT.
The Prospective Randomized Evaluation of the Vascular Effects of Norvase (amlodipine) Trial (PREVENT) was designed specifically to assess if amlodipine can be shown to inhibit angiographic progression of lesions 30% or less diameter stenosis. A carotid ultrasound substudy was also undertaken. The antiatherosclerotic effects were discordant in that minor coronary lesions were not affected, whereas carotid intima-media thickness showed significantly less progression in the amlodipine-treated patients. Moreover, significant cardiac events, particularly admissions to hospital for unstable angina and intervention, were significantly reduced in the amlodipine-treated patients. This brief report provides an overview and assessment of the implications of these findings.
Amlodipine↗
Primary stenting versus balloon angioplasty in occluded coronary arteries: the Total Occlusion Study of Canada (TOSCA).
BACKGROUND: Balloon angioplasty (PTCA) of occluded coronary arteries is limited by high rates of restenosis and reocclusion. Although stenting improves results in anatomically simple occlusions, its effect on patency and clinical outcome in a broadly selected population with occluded coronary arteries is unknown. METHODS AND RESULTS: Eighteen centers randomized 410 patients with nonacute native coronary occlusions to PTCA or primary stenting with the heparin-coated Palmaz-Schatz stent. The primary end point, failure of sustained patency, was determined at 6-month angiography. Repeat target-vessel revascularization, adverse cardiovascular events, and angiographic restenosis (>50% diameter stenosis) constituted secondary end points. Sixty percent of patients had occlusions of >6 weeks' duration, baseline flow was TIMI grade 0 in 64%, and median treated segment length was 30.5 mm. With 95.6% angiographic follow-up, primary stenting resulted in a 44% reduction in failed patency (10.9% versus 19.5%, P=0.024) and a 45% reduction in clinically driven target-vessel revascularization at 6 months (15.4% versus 8.4%, P=0.03). The incidence of adverse cardiovascular events was similar for both strategies (PTCA, 23.6%; stent, 23.3%; P=NS). Stenting resulted in a larger mean 6-month minimum lumen dimension (1.48 versus 1.23 mm, P<0.01) and a reduced binary restenosis rate (55% versus 70%, P<0.01). CONCLUSIONS: Primary stenting of broadly selected nonacute coronary occlusions is superior to PTCA alone, improving late patency and reducing restenosis and target-vessel revascularization.
Adolescent↗
Reporting risks and benefits of therapy by use of the concepts of unqualified success and unmitigated failure: applications to highly cited trials in cardiovascular medicine.
BACKGROUND: The NNT (number needed to treat) and NNH (number needed to harm) are useful in conveying the results of clinical trials because they emphasize the effort that must be expended to accomplish a single, tangible outcome. But NNT conveys the effort required to achieve a positive outcome without distinguishing between the presence or absence of treatment-related adverse events. Similarly, NNH conveys harm without accounting for the achievement or lack of achievement of the benefit of therapy. Consequently, a mathematical model was developed to extend the NNT and NNH to represent the effort required to achieve "unqualified success" (NNTUS, treatment success without treatment-induced side effects) and "unmitigated failure" (NNHUF, lack of treatment success with treatment-induced side effects). METHODS AND RESULTS: NNTUS was calculated by adjusting the absolute risk reduction to allow for the probability of not incurring a treatment-related adverse event. NNHUF was similarly calculated by adjusting the absolute risk of incurring a treatment-related adverse event by the probability of not incurring any treatment-related benefit. The impact of conveying clinical trial data by the use of NNT, NNTUS, NNH, and NNHUF is illustrated by means of 11 highly cited trials identified systematically from the cardiovascular literature. The treatment effort measured by the NNTUS and the NNHUF was consistently higher than that given by the traditional NNT and NNH. These increments ranged from 1% to several hundred percent. CONCLUSIONS: The NNTUS and the NNHUF represent the treatment effort required on average to achieve 1 unqualified success and 1 unmitigated failure. NNTUS and NNHUF balance benefit and harm in an objective way and are relevant for making service delivery decisions.
Cardiovascular Diseases↗
Retrieval and analysis of particulate debris after saphenous vein graft intervention.
OBJECTIVES: This study was designed to evaluate the composition and quantity of particulate debris resulting from vein graft intervention. BACKGROUND: Distal embolization and "no reflow" are frequent and important complications resulting from angioplasty of diseased saphenous vein grafts. Little is known about the composition and quantity of embolic particulate debris associated with vein graft intervention, and no intervention has been shown to protect against its clinical consequences. METHODS: A catheter system, designed to contain, retrieve and protect against distal embolization of this material, was evaluated during 27 percutaneous interventional saphenous vein graft procedures. Clinical, angiographic and pathologic analyses were performed. RESULTS: The duration of distal graft occlusion required to allow intervention and subsequent debris removal was 150 +/- 54 s, decreasing as experience was gained. Thrombolysis in Myocardial Infarction trial (TIMI) flow grade increased from 2.6 +/- 0.8 to 3.0 +/- 0.0. Creatine kinase (CK) rose above normal in three patients (11.1%) exceeding 3x normal in one (3.7%) resulting in the diagnosis of non-Q-myocardial infarction. Particulate material was identified following 21 of 23 procedures suitable for analysis. Particle size was 204 +/- 57 microm in the major axis and 83 +/- 22 microm in the minor axis. Particles consisted predominantly of soft acellular atheromatous material, such as that typically found under a fibrous cap. Semiquantitative analysis suggested that the quantity of particulate material was less following stenting than following balloon dilation. CONCLUSIONS: Particulate matter is commonly present following routine angioplasty and stenting of saphenous vein grafts. Containment, retrieval and analysis of this particulate debris are all feasible. Comparison to prior clinical experience is limited by small sample size. However, to the extent that these particles may contribute to distal embolization, no-reflow and infarction, such a system may contribute to the reduction of complications following vein graft intervention.
Aged↗
Influence of smoking status on angiotensin-converting enzyme inhibition-related improvement in coronary endothelial function. TREND Investigators. Trial on Reversing Endothelial Dysfunction.
Our study evaluated the influence of smoking status on coronary endothelial function in normotensive patients with coronary artery disease who received placebo or the angiotensin-converting enzyme inhibitor quinapril in the TREND study (Trial on Reversing Endothelial Dysfunction). In this retrospective analysis of data from the previously published study, patients were classified as either smokers (n = 23) or nonsmokers (n = 82). Patients underwent coronary angiography at baseline and again after 6-month follow-up. The primary response variable was the net change in acetylcholine-induced diameter of the target coronary artery segments (n = 105) between the baseline and 6-month follow-up angiograms. The secondary response variables were based on analysis of all segments (n = 300) and the mean diameter responses of target and all segments at 6 months. At baseline, coronary artery vasomotor responses were similar in smokers and nonsmokers in the placebo and quinapril groups. There was a significant improvement in the primary response variable for both smokers (P = 0.008) and nonsmokers (P = 0.047) randomized to quinapril compared with placebo. At 6-month follow-up, nonsmokers in the placebo group showed no significant change in the mean vasoconstrictor responses (8.3% vs. 8.0% at acetylcholine 10(-4) mol/L), whereas nonsmokers in the quinapril-treated group showed significantly less vasoconstriction (2.7% vs. 13.2%; P = 0.003). Among smokers in the placebo group, vasoconstriction increased nonsignificantly (21.7% vs. 17.2% at baseline) but decreased significantly in the quinapril group (0.5% vs. 17.9%; P = 0.002). These results indicate that ACE inhibition improves the coronary vasomotor response in both smokers and nonsmokers, but that smokers apparently derive greater benefit.
Acetylcholine↗
Carotid intima-media thickness measurements: what defines an abnormality? A systematic review.
OBJECTIVE: In light of tremendous interest in and speculation about the implications of carotid artery intima-media thickness (IMT) measurements in clinical decision-making, the authors reviewed currently available information on IMT measurements in normal subjects and created a framework that can be used to define an abnormal result. DATA SOURCES: A search of MEDLINE and Current Contents, complemented by detailed analysis of references in the papers identified. STUDY SELECTION: Population studies pertaining to IMT measurements in normal subjects were selected. DATA EXTRACTION: Methods of measurement of carotid artery IMT, mean IMT by age and sex, IMT progression rates, and relation of IMT to risk of coronary and cerebrovascular events. DATA SYNTHESIS: Although reports were from different populations and used differing techniques and equipment, the reported IMT measurements showed a consistent progression with age and greater values among men. Studies comparing the IMT between abnormal and normal groups show that most of the abnormal IMT measurements are above the 75th percentile of the mean common carotid artery IMT in normal subjects. Studies relating IMT measurements to the risk of coronary and cerebrovascular events show that the risk of first myocardial infarction increases with an IMT of 0.822 mm or more and the risk of stroke with an IMT of 0.75 mm or more. A progression rate of the far-wall common carotid artery IMT of 0.034 mm per year or greater increases the risk of future events significantly. CONCLUSIONS: An aggregated framework based on studies in differing age groups may be useful for assessing carotid vascular abnormalities as an aid to defining abnormalities and predicting risk in individual patients.
Adolescent↗
Detection of early atherosclerosis with B mode carotid ultrasonography: assessment of a new quantitative approach.
PURPOSE: To examine the relation between carotid artery (CA) intima-media thickness (IMT) assessed by B mode ultrasonography (US), presence of plaques and major risk factors in a population without known vascular disease. Alternative methods of quantifying US results and implications for starting lipid-lowering therapy were also explored. DESIGN: Prospective study. SETTING: Specialized lipid clinic. PATIENTS: One hundred and sixty patients with hyperlipidemia but without symptomatic coronary or peripheral vascular disease were examined by US, of whom 92 patients with normal blood pressure who were not receiving lipid-lowering treatment were included in the analysis. INTERVENTIONS: B mode US of the CA was performed. Measurements were made of the IMT of the right and left common CA, and the average IMT (AIMT) was calculated. The number of plaques (PN) in the CA and its bifurcations was counted, and the average total thickness (ATT), the total area (TA), and average plaque thickness (APT) were calculated. RESULTS: Stepwise regression analysis showed that age, the ratio of total cholesterol to high-density-lipoprotein cholesterol, weight and smoking significantly predicted ATT, APT and PN. By contrast, age, weight and apo B levels predicted AIMT. Detection of patients with CA abnormalities was improved by incorporating plaque dimensions: AIMT had a 63% sensitivity in detecting CA abnormalities, whereas TA had a sensitivity of 72%. CONCLUSION: Indices of CA atherosclerosis that integrate the contribution of plaque to overall atheroma burden are related to known risk factors and are more sensitive than AIMT for detection of abnormalities.
Adolescent↗