Inflammation and restenosis: is there a link?
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Biomedical subjects
Publications and source records attributed to Deepak L Bhatt.
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BACKGROUND: Clopidogrel is a more potent antiplatelet agent than aspirin, resulting in greater clinical efficacy in patients with atherothrombotic disease. Furthermore, the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown. METHODS AND RESULTS: The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study was designed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary, cerebral, or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event. This randomized, international, multicenter, double-blinded, placebo-controlled study has finished enrolling patients worldwide. A total of 15,603 patients will be followed long term. The primary end point will be the composite of vascular death, myocardial infarction, or stroke. Rates of severe bleeding will also be compared between the two arms of the study. CONCLUSIONS: This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current standard of care, including low-dose aspirin, for a wide spectrum of patients with atherothrombosis.
BACKGROUND: Prior reports have suggested that women have increased mortality compared to men following percutaneous coronary intervention (PCI). It remains unclear if this difference is secondary to sex or other confounding variables. METHODS: We sought to examine the characteristics and outcomes of 18039 consecutive women and men undergoing PCI at The Cleveland Clinic Foundation from 1992-2002. RESULTS: Procedural success rates were similar in both sexes, but the female cohort had a greater incidence of access site hematoma (5% vs. 2%, P < .0001) and blood product transfusion (12% vs. 4%, P < .0001) following PCI. The rate of myocardial infarction (MI) at 1 year was slightly higher among females (10% vs. 9%, P = .004), but revascularization rates were not significantly different between sexes. One-year mortality was also higher in the female cohort (7% vs. 5%, P < .0001). After adjustment in a multivariate model, the Cox proportional hazard ratio for mortality in females was 1.01 (95% CI 0.93-1.11, P = .78). The hazard ratio for the combined endpoint of death or MI was 1.05 (95% CI 0.97-1.13, P = .23). CONCLUSIONS: After adjustment for differences in comorbidities, the risk for long-term mortality is not significantly different between sexes following PCI. However, there is a greater incidence of post-procedural bleeding complications among women.
BACKGROUND: Use of emboli protection devices (EPD) during saphenous vein graft percutaneous coronary intervention (SVG-PCI) has been proven to reduce major adverse cardiac events (MACE). However, the impact of EPD on the microcirculation using Thrombolysis in Myocardial Infarction myocardial perfusion grade (TMP) has not been fully characterized. We sought to analyze TMP after SVG-PCI with and without EPD and determine its impact on inhospital MACE. METHODS: From August 2001 to December 2002, 305 patients had SVG-PCI suitable for EPD; 210 (69%) had an angiogram appropriate for TMP evaluation. Of those, 46 (22%) had an EPD (GuardWire, Medtronic, Minneapolis, Minn) deployed during the coronary intervention. Both groups were similar with regard to most demographic and clinical features. RESULTS: A TMP score of 2.5 or 3 was obtained in 98% of the EPD group versus 85% of the unprotected SVG-PCI (P = .01). There was a trend towards reduction in MACE when using EPD (15% vs 27%, respectively, P = .07). Peak postprocedural creatine kinase-MB was somewhat lower in the EPD group (6.03 +/- 7.8 ng/mL vs 14.87 +/- 42 ng/mL, P = .17) Patients with a TMP grade of 2.5 or 3 had a statistically significant reduction in MACE (OR 0.36, 95% CI 0.14-0.87, P = .02). CONCLUSIONS: Compared with SVG-PCI without emboli protection, EPD significantly improved TMP and trended towards a reduction in MACE.
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Widespread adoption of the antiplatelet agents into everyday clinical practice has revolutionized contemporary care of the cardiovascular patient. Major adverse cardiovascular events including death, myocardial infarction, stroke, and recurrent angina have all been shown to be significantly decreased when these agents are employed in the treatment of coronary atherosclerosis, acute coronary syndromes, myocardial infarction, and in the setting of percutaneous coronary intervention. As a growing number of patients on antiplatelet therapy are undergoing various surgical procedures, the potential risks and benefits these drugs pose perioperatively will become increasingly important. Available data indicate that, when used appropriately, these drugs can be used safely prior to surgery. Efficacy in improving surgical outcomes and in preventing adverse cardiovascular events postoperatively has also been demonstrated. The purpose of this review is to examine the perioperative safety and efficacy of the most widely used antiplatelet agents: aspirin; the thienopyridine clopidogrel; and the glycoprotein (GP) IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban. This information, coupled with emerging platelet monitoring techniques, may help provide additional assistance to the clinician to manage therapy and guide appropriate timing of both cardiac and noncardiac surgery.
Platelet activation is a pivotal event in the pathophysiology of acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) and has a substantial impact on the outcomes in these settings. Aggressive implementation of antiplatelet therapy has significantly decreased adverse cardiovascular events, such as death, myocardial infarction (MI), stroke, and repeat revascularization. Although the widespread use of aspirin has contributed to this improvement, many patients continue to have a significant risk of recurrent events during the ensuing months to years. The advent of other antiplatelet agents, notably the thienopyridine clopidogrel bisulfate has heralded a new era of combined antiplatelet blockade, offering the hope of better outcomes. Recently, clinical trials have tested the use of dual oral antiplatelet blockade and have shown impressive results. Notably, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found that dual therapy with clopidogrel and aspirin in ACS reduced adverse cardiovascular events by 20% at 1 year (p < 0.001). The PCI-CURE substudy of CURE and the Clopidogrel for the Reduction of Events During Observation (CREDO) trial demonstrated that these benefits extend to patients undergoing both urgent and elective PCI. This article will explore the current role of and controversies in oral antiplatelet therapy after ACS and PCI.
PURPOSE OF REVIEW: Inflammatory vascular diseases are initiated and perpetuated by the interaction of immune cells with cells of the affected vessel wall. This is directed by a network of chemical messengers, which, in a state of vascular health, exist as balanced but opposing forces. Our understanding of this highly complex process has advanced significantly in the last several decades. The detection of vascular inflammation and monitoring of this activity have long been attempted in systemic vasculitis, and, more recently, in atherosclerosis. Markers of vascular inflammation used thus far have been of limited value; few provide both adequate sensitivity and specificity for any particular disease. New insights into the pathophysiology of vascular inflammation have identified other potential markers that may improve detection and monitoring of these conditions. RECENT FINDINGS: Immunomodulatory mediators of the inflammatory cascade have been identified, and their roles are being defined. There are recent data that implicate various cytokines, proteases, adhesion molecules, and acute phase proteins as participants in the generation of vascular inflammation. CONCLUSION: The pursuit of highly sensitive and specific markers of vascular inflammation has produced a wealth of information that has been instrumental in advancing our comprehension of this complex process. Further studies will establish the role of these new markers in the diagnosis, monitoring, and prognostication of inflammatory vascular disease.
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OBJECTIVES: This study was designed to assess the feasibility and safety of enoxaparin in combination with glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) as part of an early invasive strategy in patients presenting with acute coronary syndromes (ACS). BACKGROUND: Trials in patients with ACS have evaluated the utility of enoxaparin, adjuvant GP IIb/IIIa inhibitors with PCI, and an early invasive approach. Information about the combination of all three of these approaches, however, is limited. METHODS: Forty-nine patients with ACS underwent cardiac catheterization, of whom 23 underwent PCI with enoxaparin and GP IIb/IIIa inhibitors. RESULTS: The primary endpoint of the study, a composite of death, myocardial infarction or urgent revascularization at 30 days, occurred in 8% of patients undergoing PCI. There were no deaths. One patient received a blood transfusion. No other adverse events occurred. These event rates were comparable to those from the pooled EPILOG/EPISTENT database, in which intravenous unfractionated heparin was used in conjunction with GP IIb/IIIa receptor blockade. The mean anti-Xa level in patients undergoing PCI was 0.74 0.48 U/ml. The majority of patients who underwent PCI within eight hours of their last dose of enoxaparin had therapeutic anti-Xa levels. CONCLUSION: In patients with ACS, enoxaparin in combination with GP IIb/IIIa inhibitors and an early invasive approach resulted in comparable clinical complication and bleeding rates versus historical references utilizing unfractionated heparin.
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We describe a case of carotid artery restenosis following carotid artery stenting for treatment of post-endarterectomy stenosis. The goal is to highlight the risk of recurrent restenosis following endarterectomy. In this case report, we describe the use of cutting balloon therapy as a reasonable alternative to repeat surgical revascularization.
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One of the more common regular supraventricular tachyarrhythmias encountered in clinical practice is atrioventricular nodal re-entrant tachycardia (AVNRT). Catheter-based radiofrequency ablation is becoming a common modality for the treatment of symptomatic tachyarrhythmias. It is safe and effective, but complications can occur. We present a patient with asymptomatic acute inferior ST elevation myocardial infarction from thermal injury following radiofrequency modification of the slow pathway for the treatment of AVNRT. This case illustrates an unusual mechanism leading to acute myocardial infarction as a complication of a commonly performed electrophysiology procedure that should be recognized by both interventionalists and electrophysiologists and treated aggressively with percutaneous revascularization.
Atherosclerosis is a pathological process caused by vascular remodeling. It symbolizes one of the major causes for morbidity and mortality in the western world. The causes for these vascular problems are manifold and different etiologies have been discussed. Since the 1980s the role of chronic inflammation has been considered and is now confirmed by many studies and experimental data. Several inflammatory pathways have been shown to participate in the atherosclerotic process. Different markers for inflammation have been found to predict the future risk for developing cardiovascular disease. Among these, high sensitivity C-reactive protein has been the most extensively validated. Newer markers such as CD40 ligand appear also to provide important information regarding risk stratification. Medications have been found to lower levels of inflammatory markers and perhaps decrease the associated clinical risk. Statins particularly appear to have anti-inflammatory mediated benefits, though other classes of drugs are also being evaluated. Lipid-lowering therapy in general has been found to be associated with reductions in inflammatory markers. Antithrombotic therapy, such as intravenous glycoprotein lIb/IIIa inhibitors and clopidogrel, has also been demonstrated to reduce inflammatory marker release. Peroxisome proliferator-activated receptor agonists are being evaluated for possible roles in targeting arterial inflammation. Angiotensin-converting enzyme inhibitors may also have anti-inflammatory properties. In this article we review the existing data in the inflammatory model of atherosclerosis. Furthermore, we discuss the prognostic value of different inflammatory markers and the potential benefit of anti-inflammatory therapies in cardiovascular disease.
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Using univariate and multivariate analyses, we evaluated the relation between ischemic and bleeding complications and peak procedural activated clotting time (ACT) in patients undergoing percutaneous coronary intervention whose coronary narrowings were treated with stent implantation. Of the 2,280 patients who qualified for the study, 29% had diabetes mellitus, and 91% received glycoprotein IIb/IIIa inhibitors. The median for ACT was 276 seconds (interquartile range 243 to 317). The incidence of ischemic events by ACT quartiles was 6.3%, 7.5%, 8.1%, and 7.1%, respectively (p=0.71). The incidence of bleeding complications was 6.6%, 5.9%, 6.9%, and 7.3%, respectively (p=0.81). ACT did not independently predict either ischemic or hemorrhagic complications.
Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.