Non-acute Coronary Artery Disease Research Articles

Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

Percutaneous coronary intervention versus medical therapy for stable coronary artery disease: Meta-regression analysis of mortality and morbidity against stent use

In a meta-analysis of randomized trials enrolling patients with stable coronary artery disease (CAD), Wijeysundera et al. [1] found that percutaneous coronary intervention (PCI) was associated with greater freedom from angina compared with medical therapy. Meanwhile, a meta-analysis by Jeremias et al. [2] of randomized trials demonstrated that revascularization by PCI in conjunction with medical therapy in patients with non-acute CAD was associated with significantly improved survival compared with medical therapy alone. Most trials included in the meta-analysis, however, compared medical therapy with balloon angioplasty without stenting. In a metaanalysis by Trikalinos et al. [3] summarizing head-to-head (direct) comparisons (only 4 randomized trials) in patients with non-acute CAD, succeeding advancements in PCI with stenting (bare metal) compared with medical therapy did not produce detectable improvements in deaths or myocardial infarction (MI). Also in their network meta-analyses integrating direct and indirect evidence, the point estimates were similar to the direct comparisons. To assess the impact of stenting in the comparison of PCI versus medical therapy in patients with stable CAD, we performed a meta-regression analysis using data of 9497 patients from randomized trials identified in the most recent and comprehensive (published in 2010 with literature search through June 2009) systematic review by Wijeysundera et al. [1]. The analyzed studies were 19 randomized trials: 15 trials [4–18] included in the meta-analysis by Wijeysundera et al. [1]; and 4 trials [19–22] excluded in it [1] because of not reporting on angina. We included 10-year results of the Medicine, Angioplasty, or Surgery Study (MASS II) [14] instead of 5-year outcomes. For each study, data regarding all-cause/cardiac death and any/non-fatal MI in both the PCI andmedical therapy groupswere used to generate odds ratio (ORs) and 95% confidence intervals (CIs). Study-specific estimates were combined using Mantel–Haenzel methods in both fixedand random-effects models. We developed a mixed-effects (unrestricted maximum likelihood) meta-regression model by plotting the natural logarithm of the OR for each outcome against the proportion of patients undergoing stenting in the PCI group. All analyses were conducted using Review Manager version 5.0 (Nordic Cochrane Centre, Copenhagen, Denmark) and Comprehensive Meta-Analysis version 2 (Biostat, Englewood, NJ). Pooled analysis (5470 patients) demonstrated a statistically significant 42% reduction in cardiac death with PCI relative to medical therapy in the fixed-effects model (OR, 0.58; 95% CI, 0.44 to 0.77; p=0.0001; p for heterogeneity=0.24; Fig. 1A). In the meta-regression analysis, we observed a statistically significant positive relationship between the proportion of stenting and the risk of cardiac death (p=0.02; Fig. 1B).When data from 5 stent-predominant trials (proportionof patientsundergoingstenting≥50% [N70% in all the5 trials])were pooled (3074 patients), PCI was not associated with a reduction in cardiac death relative to medical therapy (fixed-effects OR, 0.74; 95% CI, 0.52 to 1.06; p=0.10; p for heterogeneity=0.78; Fig. 1A). Meanwhile, pooled analysis demonstrated no statistically significant differences in all-cause death (fixed-effects OR, 0.89; 95% CI, 0.78 to 1.03; p=0.11; p for heterogeneity=0.30), anyMI (fixed-effects OR,1.18; 95%CI, 0.97 to 1.44; p=0.10; p for heterogeneity=0.33), and non-fatal MI (randomeffects OR, 0.99; 95% CI, 0.66 to 1.49; p=0.98; p for heterogeneity=0.0004).In the meta-regression analyses, we observed no statistically significant relationship between the proportion of stenting and the risk of all-cause death (p=0.16), any MI (p=0.91), or non-fatal MI (p=0.16). The results of our analysis suggest that PCImay reduce cardiac death by 37% over medical therapy in patients with stable CAD. The previous meta-analysis by Jeremias et al. [2] of 21 randomized trials also demonstrated that, compared with medical therapy alone, coronary artery revascularization by PCI for non-acute CADwas associated with a significant reduction in mortality (OR, 0.82; 95% CI, 0.68 to 0.99). However, 17 of the 21 trials compared medical therapy with balloon angioplasty without stenting, and in the remaining only 4 trials bare metal stents were implanted in 72% to 100% of cases. For only 4 randomized direct comparisons of PCI with bare metal stents versus medical therapy in another previous meta-analysis, Trikalinos et al. [3] recorded no significant differences for death (risk ratio [RR], 0.96; 95% International Journal of Cardiology 150 (2011) 90–120

Prevalence of diabetes in patients with nonacute CAD

The relationship between coronary artery disease (CAD) and diabetes is widely documented [1–3], and diabetic patients present a worse CV outcome in respect to nondiabetic patients [4]. Recently, the physiopathology of CV risk in patients affected by undiagnosed or newly detected diabetes is matter of great interest [5, 6]. Actually, the prevalence of diabetes in CAD patients is not clearly estimated because diagnosis is generally based on not exhaustive criteria, such as history of diabetes or hyperglycemia during acute events. We aimed to evaluate the true prevalence of diabetes in nonacute patients affected by CAD, as assessed by coronary angiography. Six hundred and seventy nine patients admitted from November 2008 to November 2009 in the Cardiology Ward of University of Naples to perform angiography for suspect CAD were assessed for eligibility. Patients with coronary acute events in the last 4 week and subjects without angiographically detectable CAD were excluded. Moreover, treatment with steroids, acute infections, fever, or any condition that could impair glycemic metabolism were further exclusion criteria. Finally, 510 Caucasian patients (301M, 209F; age 57 ± 13 years) were eligible. Ninety seven (19%) had known diabetes (history and/or use of antidiabetic agents or newly discovered by fasting glucose value C126 mg/dl). The other 413 were submitted to standardized oral glucose test tolerance (OGTT), repeated twice in case of abnormal response [7]. Diabetes was revealed in 151 subjects, while 72 were affected by prediabetes, a condition at high risk to develop overt diabetes. Thus, the overall prevalence of diabetes was 48.6%, and the prevalence of glycemic impairments (diabetes plus prediabetes) was 62.7%. Only 190 (37.2%) showed a normal glucose tolerance (Fig. 1). The number of vessels with obstructive plaque (C50% lumen narrowing) was higher in diabetic than in nondiabetic group (1.12 ± 1.13 vs. 1.68 ± 1.33; P \ 0.01),

Cardiogoniometric parameters for detection of coronary artery disease at rest as a function of stenosis localization and distribution

Cardiogoniometry (CGM), a spatiotemporal electrocardiologic 5-lead method with automated analysis, may be useful in primary healthcare for detecting coronary artery disease (CAD) at rest. Our aim was to systematically develop a stenosis-specific parameter set for global CAD detection. In 793 consecutively admitted patients with presumed non-acute CAD, CGM data were collected prior to elective coronary angiography and analyzed retrospectively. 658 patients fulfilled the inclusion criteria, 405 had CAD verified by coronary angiography; the 253 patients with normal coronary angiograms served as the non-CAD controls. Study patients--matched for age, BMI, and gender--were angiographically assigned to 8 stenosis-specific CAD categories or to the controls. One CGM parameter possessing significance (P < .05) and the best diagnostic accuracy was matched to one CAD category. The area under the ROC curve was .80 (global CAD versus controls). A set containing 8 stenosis-specific CGM parameters described variability of R vectors and R-T angles, spatial position and potential distribution of R/T vectors, and ST/T segment alterations. Our parameter set systematically combines CAD categories into an algorithm that detects CAD globally. Prospective validation in clinical studies is ongoing.

Atherosclerotic renovascular disease in the United States

Atherosclerotic renovascular disease (ARVD) is an increasingly recognized clinical condition that is diagnosed predominantly in older patients. Here we used annual United States Medicare 5% Denominator Files and studied 16,036,904 patients, 66 years of age and older, to quantify trends in diagnostic rates, associations, treatment, and outcomes of ARVD over a 13-year period. Overall, there was an ARVD rate of 3.09 per 1000 patient-years, which rose progressively with an adjusted hazard ratio of 3.35, comparing data from 1992 to 2004. Within 6 months of disease diagnosis, 13.4% of patients had undergone revascularization. A biphasic pattern of revascularization was found where the adjusted hazard ratios significantly increased in a progressive manner until 1999, following which there was a decline through 2004, which was not significant. The method of revascularization changed markedly over time with endovascular intervention steadily replacing direct surgical revascularization. As a time-dependent variable, ARVD was associated with excess mortality in each calendar year, albeit with declining hazard ratio estimates in more recent years. Among patients with this disease, revascularization was associated with mortality adjusted hazard ratios <1 in each year. Our study shows the diagnosis of ARVD has substantially risen in the United States but the survival implications were not fully explained by other comorbid vascular diseases.

Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis

Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis

Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis

Over the past 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare-metal stents (BMS), and drug-eluting stents (DES) succeeded each other as catheter-based treatments for coronary artery disease. We undertook a systematic overview of randomised trials comparing these interventions with each other and with medical therapy in patients with non-acute coronary artery disease. We searched Medline for trials contrasting at least two of the four interventions (PTCA, BMS, DES, and medical therapy). Eligible outcomes were death, myocardial infarction, coronary artery bypass grafting, target lesion or vessel revascularisation, and any revascularisation. Random effects meta-analyses summarised head-to-head (direct) comparisons, and network meta-analyses integrated direct and indirect evidence. 61 eligible trials (25 388 patients) investigated four of six possible comparisons between the four interventions; no trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in percutaneous coronary intervention did not produce detectable improvements in deaths or myocardial infarction. The risk ratio (RR) for indirect comparisons between DES and medical therapy was 0.96 (95% CI 0.60-1.52) for death and 1.15 (0.73-1.82) for myocardial infarction. By contrast, we recorded sequential significant reductions in target lesion or vessel revascularisation with BMS compared with PTCA (RR 0.68 [0-60.0.77]) and with DES compared with BMS (0.44 [0.35-0.56]). The RR for the indirect comparison between DES and PTCA for target lesion or vessel revascularisation was 0.30 (0.17-0.51). Sequential innovations in the catheter-based treatment of non-acute coronary artery disease showed no evidence of an effect on death or myocardial infarction when compared with medical therapy. These results lend support to present recommendations to optimise medical therapy as an initial management strategy in patients with this disease.

Effectiveness of PCI for non-acute coronary artery disease

Effectiveness of PCI for non-acute coronary artery disease

The Impact of Revascularization on Mortality in Patients with Nonacute Coronary Artery Disease

Background Although early revascularization improves outcomes for patients with acute coronary syndromes, the role of revascularization for patients with nonacute coronary artery disease is controversial. The objective of this meta-analysis was to compare surgical or percutaneous revascularization with medical therapy alone to determine the impact of revascularization on death and nonfatal myocardial infarction in patients with coronary artery disease. Methods The Medline and Cochrane Central Register of Controlled Trials databases were searched to identify randomized trials of coronary revascularization (either surgical or percutaneous) versus medical therapy alone in patients with nonacute coronary disease reporting the individual outcomes of death or nonfatal myocardial infarction reported at a minimum follow-up of 1 year. A random effects model was used to calculate odds ratios (OR) for the 2 prespecified outcomes. Results Twenty-eight studies published from 1977 to 2007 were identified for inclusion in the analysis; the revascularization modality was percutaneous coronary intervention in 17 studies, coronary bypass grafting in 6 studies, and either strategy in 5 studies. Follow-up ranged from 1 to 10 years with a median of 3 years. The 28 trials enrolled 13,121 patients, of whom 6476 were randomized to revascularization and 6645 were randomized to medical therapy alone. The OR for revascularization versus medical therapy for mortality was 0.74 (95% confidence interval [CI], 0.63-0.88). A stratified analysis according to revascularization mode revealed both bypass grafting (OR 0.62; 95% CI, 0.50-0.77) and percutaneous intervention (OR 0.82; 95% CI, 0.68-0.99) to be superior to medical therapy with respect to mortality. Revascularization was not associated with a significant reduction in nonfatal myocardial infarction compared with medical therapy (OR 0.91; 95% CI, 0.72-1.15). Conclusion Revascularization by coronary bypass surgery or percutaneous intervention in conjunction with medical therapy in patients with nonacute coronary artery disease is associated with significantly improved survival compared with medical therapy alone.

Are “treatment” bare metal stents superior to “control” bare metal stents? A meta-analytic approach

It has been suggested that the benefits of drug-eluting stents compared to bare metal stents (BMS) have been overestimated in part because target lesion/vessel revascularization (TLR/TVR) rates in the BMS control group of these trials were spuriously high. We used meta-analytic techniques to systematically compare clinical event rates among patients treated with BMS in trials where BMS were the experimental (BMS(experimental)) rather than the control (BMS(control)) intervention. MEDLINE searches were performed to identify eligible randomized trials comparing either drug-eluting stents with BMS(control) or BMS(experimental) with balloon angioplasty in patients with nonacute coronary artery disease. Trial characteristics and 6- to 12-month rates for death, myocardial infarction, TLR/TVR, and major adverse cardiac events were extracted and assessed. Eligible trials yielded 50 BMS cohorts: 19 in the BMS(control) group (4046 patients) and 31 in the BMS(experimental) group (5068 patients). Summary death and infarction rates did not differ between groups. The summary TLR/TVR rates were 16.2% (95% CI 13.5-19.3) versus 13.8% (95% CI 12.0-15.7) in BMS(control) versus BMS(experimental) groups, respectively (P = .15). Among 39 BMS cohorts with < or = 250 patients, TLR/TVR rates were significantly higher in BMS(control) versus BMS(experimental) groups (18.9% [95% CI 16.0-22.2] vs 13.7% [95% CI 11.5-16.3], P = .01). There were no between-group differences among larger BMS cohorts (P = .98). Although overall clinical event rates did not differ in the BMS(control) and the BMS(experimental) groups, a higher rate of TVR/TLR was seen in the BMS(control) group among smaller trials.

Dynamics of heart failure and left ventricular parameters in patients with nonacute coronary artery disease and recurrent ischaemia after percutaneous revascularization

Dynamics of heart failure and left ventricular parameters in patients with nonacute coronary artery disease and recurrent ischaemia after percutaneous revascularization

The Role of Coronary Angioplasty in the Management of Patients with Stable Coronary Artery Disease

A review of the existing evidence on the impact of percutaneous coronary intervention (PCI) in the setting of stable coronary artery disease (CAD) indicates that in patients with chronic coronary artery disease and good left ventricular function, PCI does not confer any clear benefit in terms of hard long-term clinical outcomes, such as mortality, myocardial infarction or the need for subsequent revascularization, as compared with medical conservative treatment. By comparing the benefits against cost considerations, it seems that many percutaneous interventions that are currently performed in patients with non-acute CAD are probably not justified. Determination of the functional significance of coronary artery disease can often be a challenge. Conventional coronary angiography and imaging tests, although suitable for risk stratification, may not be satisfactory as independent guides for specific decision-making regarding the optimum management of these patients. The development of more efficient methods for the identification of coronary lesions that should be the target of coronary intervention is certainly needed.

Percutaneous Coronary Intervention Versus Conservative Therapy in Nonacute Coronary Artery Disease: A Meta-analysis

Percutaneous Coronary Intervention Versus Conservative Therapy in Nonacute Coronary Artery Disease: A Meta-analysis

Issue Highlights

HomeCirculationVol. 111, No. 22Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published7 Jun 2005https://doi.org/10.1161/circ.111.22.2865Circulation. 2005;111:2865FREEDOM FROM ATRIAL TACHYARRHYTHMIAS AFTER CATHETER ABLATION OF ATRIAL FIBRILLATION: A RANDOMIZED COMPARISON BETWEEN 2 CURRENT ABLATION STRATEGIES, by Karch et al.Catheter ablation for maintaining sinus rhythm increasingly is considered when atrial fibrillation is highly symptomatic despite antiarrhythmic drug therapy. Rapidly activating regions in and around the pulmonary veins are causative in many patients. Ablation techniques targeting these regions, reported results, and complications vary among centers. Comparative data for different approaches are limited. The randomized trial by Karch et al in this issue of Circulation compared 2 more commonly used approaches: ablation encircling a wide area around the pulmonary vein ostia guided by anatomy, versus an electrogram-guided approach ablating only segments of the pulmonary vein ostia. In contrast to a previous trial, the segmental ablation approach was associated with better arrhythmia control. Many recurrences were asymptomatic in both groups. Serious complications included tamponade, pulmonary vein stenosis, and thromboemboli. These findings add fuel to the continuing controversy as to the optimal method and support the practice of confining this procedure to highly symptomatic patients. See p 2875.PERCUTANEOUS CORONARY INTERVENTION VERSUS CONSERVATIVE THERAPY IN NONACUTE CORONARY ARTERY DISEASE: A META-ANALYSIS, by Katritsis and Ioannidis.Clinicians have often debated the incremental benefit of percutaneous coronary interventions for patients with stable angina. This study sought to synthesize the existing data by conducting a meta-analysis of the 11 randomized clinical trials of medical therapy versus percutaneous coronary intervention (PCI) in patients with angiographically documented coronary stenoses in nonacute coronary artery disease settings. The study specifically sought to determine whether PCI was associated with a subsequent reduction in risk of mortality, cardiac death or myocardial infarction, nonfatal myocardial infarction, and coronary artery bypass grafting or PCI. The follow-up was more than 2 years for 5 of the studies. This meta-analysis provides the best current evidence about whether PCI for patients with stable angina does more than improve symptoms. See p 2906.REDUCED NUMBER OF CIRCULATING ENDOTHELIAL PROGENITOR CELLS PREDICTS FUTURE CARDIOVASCULAR EVENTS: PROOF OF CONCEPT FOR THE CLINICAL IMPORTANCE OF ENDOGENOUS VASCULAR REPAIR, by Schmidt-Lucke et al.Endothelial function has been linked to the future risk of cardiovascular events in patients at risk. An emerging concept in vascular disease is the notion that circulating endothelial progenitor cells repopulate the vasculature to preserve normal endothelial function. Cardiovascular risk factors have been associated with a reduced number of circulating endothelial progenitor cells, suggesting that availability of these cells is key to maintaining normal vascular function. In this issue, Schmidt-Lucke and colleagues add important new information to this paradigm by demonstrating that the availability of endothelial progenitor cells is directly linked to the future incidence of cardiovascular events. See p 2981.Visit www.circ.ahajournals.org:Images in Cardiovascular MedicineSpontaneous Left Atrial Dissection Presenting as Pulmonary Edema. See p e372.ST Elevation During Open Heart Surgery: Floating Air Bubble in Saphenous Vein Graft. See p e374.Fluorine-18–Labeled Deoxyglucose Positron Emission Tomography in the Diagnosis and Management of Aortitis With Pulmonary Artery Involvement. See p e375.Download figureDownload PowerPointCorrespondenceSee p e377. Previous Back to top Next FiguresReferencesRelatedDetails June 7, 2005Vol 111, Issue 22 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.111.22.2865 Originally publishedJune 7, 2005 PDF download Advertisement

Percutaneous Coronary Intervention Versus Conservative Therapy in Nonacute Coronary Artery Disease

Percutaneous coronary intervention (PCI) has been shown to improve symptoms compared with conservative medical treatment in patients with stable coronary artery disease (CAD); however, there is limited evidence on the effect of PCI on the risk of death, myocardial infarction, and subsequent revascularization. Therefore, we performed a meta-analysis of 11 randomized trials comparing PCI to conservative treatment in patients with stable CAD. A total of 2950 patients were included in the meta-analysis (1476 received PCI, and 1474 received conservative treatment). There was no significant difference between the 2 treatment strategies with regard to mortality, cardiac death or myocardial infarction, nonfatal myocardial infarction, CABG, or PCI during follow-up. By random effects, the risk ratios (95% CIs) for the PCI versus conservative treatment arms were 0.94 (0.72 to 1.24), 1.17 (0.88 to 1.57), 1.28 (0.94 to 1.75), 1.03 (0.80 to 1.33), and 1.23 (0.80 to 1.90) for these 5 outcomes, respectively. A possible survival benefit was seen for PCI only in trials of patients who had a relatively recent myocardial infarction (risk ratio 0.40, 95% CI 0.17 to 0.95). Except for PCI during follow-up, there was no significant between-study heterogeneity for any outcome. In patients with chronic stable CAD, in the absence of a recent myocardial infarction, PCI does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.

Review: percutaneous coronary angioplasty is associated with less angina but more coronary artery bypass grafting in patients with non-acute coronary artery disease than is medical treatment

(2000) BMJ 321, 73. Bucher HC, Hengstler P, Schindler C . , et al. . Percutaneous transluminal coronary angioplasty versus medical treatment for non-acute coronary heart disease: meta-analysis of randomised...