Drug-drug interactions involving antiplatelet agents.
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Cardiovascular Diseases↗
Biomedical subjects
Debabrata Mukherjee
Publications and source records attributed to Debabrata Mukherjee.
Gamma-linolenic acid therapy of human gliomas.
OBJECTIVES: We investigated the effect of intratumoral administration of gamma-linolenic acid (GLA) in human gliomas. METHODS: We evaluated the effect of the administration of 1 mg of GLA for 7 d via a cerebral reservoir placed into the tumor bed or by direct intratumoral delivery in nine patients who had grade 4 disease and recurrent glioma after surgery, radiation, or chemotherapy. RESULTS: There was some, but not dramatic, improvement in patients' survival. No significant prolongation of life span was expected considering the advanced nature of the disease. Nevertheless, it was encouraging that GLA produced no significant side effects in any patient. Regression of the cerebral gliomas was visualized on computed tomography and magnetic resonance imaging. CONCLUSIONS: Based on results of the present and previous studies, we believe that GLA is a safe antitumor agent and that higher doses of GLA should be investigated in future studies.
Adolescent↗
Clinical perspectives on the role of anti-platelet and statin therapy in patients with vascular diseases.
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis and is associated with a several-fold increased risk of cardiovascular morbidity and mortality. Statins and anti-platelet therapy have been unequivocally shown to be beneficial in patients with coronary artery disease, but minimal data exist on the effectiveness of these agents in patients with PAD and those undergoing peripheral vascular interventions. One recent study has demonstrated that statins are very effective as secondary preventive measures in patients with PAD but continue to be underutilized in this cohort. In our institutional peripheral interventional database, after adjustment for demographics and comorbidities, statin therapy (OR=0.21, 95% CI 0.05-0.86, p=0.03) and clopidogrel therapy (OR=0.17, 95% CI 0.04-0.78, p=0.02) were both associated with a significant reduction of the composite event rate of death, myocardial infarction and stroke at 6 months. In this article, we critically review the existing literature on the role of anti-platelet and statin therapy in reducing cardiovascular events in patients with PAD. Appropriate use of these agents may significantly decrease the cardiovascular morbidity and mortality of patients with PAD.
Arteriosclerosis↗
Superficial femoral artery occlusion: nitinol stents achieve better flow and reduce the need for medications than balloon angioplasty alone.
BACKGROUND: Nitinol slotted tube stents are of great potential benefit in superficial femoral artery (SFA) interventions due to their elastic properties. However, a paucity of data exists for their efficacy in total SFA occlusions. METHODS: Using the Cleveland Clinic Foundation Peripheral Database, we identified 40 consecutive patients who underwent percutaneous revascularization for chronically occluded SFA and addressed the outcome stratifying for stent use. We evaluated the reduction in the pressure gradient across the lesion and the need for medication following revascularization. RESULTS: Of the 40 patients, twenty-six underwent balloon angioplasty alone and 14 received nitinol slotted tube stents. Patients were well matched for age and cardiovascular risk factors. Similarly, there were no differences in baseline ankle brachial index (ABI) or claudication class between the groups. Compared to angioplasty alone, stenting was associated with a greater reduction in translesional pressure gradient (72 mmHg versus 32 mmHg; p = 0.002). In addition, patients treated with stents were less likely to require post-procedure adjunctive medical treatment (7.1% versus 42.6%; p = 0.03). CONCLUSION: In SFA occlusion, stenting results in greater reduction in translesional pressure gradient and reduced need for adjunctive medical treatment.
Aged↗
Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials.
BACKGROUND: Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. METHODS AND RESULTS: A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P=0.006) and 6 months (4.7% versus 2.0%, P<0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63; P<0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6% in the placebo group (odds ratio, 1.38; 95% CI, 0.85 to 2.24; P=0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72; P=0.07). CONCLUSIONS: Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.
Abciximab↗
Outcome of acute myocardial infarction in patients with prior coronary artery bypass grafting treated with combination reduced fibrinolytic therapy and abciximab.
ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.
Abciximab↗
A common sense approach to perioperative evaluation.
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Cardiovascular Diseases↗
Cox-2: where are we in 2003? - Cardiovascular risk and Cox-2 inhibitors.
Selective cyclooxygenase-2 (COX-2) inhibitors were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents. However, COX-2 inhibitors decrease prostacyclin production and may disrupt the normal homeostatic balance, leading to a prothrombotic state and offsetting the potential gastrointestinal benefits. Available clinical data and basic biological studies raise significant concern about the potential prothrombotic effect of this class of drugs. Two recent studies with a newer, more selective COX-2 inhibitor have added to the already existing concern about the cardiovascular safety of these agents. The widespread use of these agents mandates prospective, randomized evaluation of the cardiovascular safety of COX-2 inhibitors.
Animals↗
Missed opportunities to treat atherosclerosis in patients undergoing peripheral vascular interventions: insights from the University of Michigan Peripheral Vascular Disease Quality Improvement Initiative (PVD-QI2).
BACKGROUND: Peripheral vascular disease is a manifestation of systemic atherosclerosis and is associated with an increased risk of cardiovascular morbidity and mortality. METHODS AND RESULTS: We examined clinical outcomes in 66 consecutive patients undergoing peripheral vascular interventions at our institution between January 2001 and October 2001. At hospital discharge and at 6 months, lifestyle modifications and use of evidence-based therapy was suboptimal. At 6 months, a significant proportion continued to smoke (22.7%) and only half of the patients exercised, controlled their weight, or modified their diet for lipid control. The use of antiplatelet therapy was 77.2%; of angiotensin-converting enzyme, 35.9%; of beta-blockers, 42.5%; and of statins, 50%. Twelve of the 66 patients (18.2%) had a clinical event of death, myocardial infarction, or stroke. An appropriateness algorithm for use of secondary prevention measures was created with the use of evidence-based therapy guidelines, and a composite appropriateness variable was also created. The use of evidence-based therapy was associated with a significant reduction of the composite of death, myocardial infarction, and stroke at 6 months (OR 0.02, 95% CI 0.01 to 0.44, P=0.01). CONCLUSIONS: Atherosclerosis risk factors are very prevalent in patients with peripheral vascular disease, but these patients receive less than optimal treatment after a predominantly technical vascular intervention. Effective secondary prevention with appropriate lifestyle interventions and evidence-based medical therapy needs to be strongly encouraged and implemented in these patients.
Algorithms↗
(1SR,2RS,5RS,6SR,8RS)-7,7-Dimethyltricyclo[6.2.1.0(1,6)]undecane-2,5,6-triol: a supramolecular framework built from O-H...O hydrogen bonds.
In the title compound, C(13)H(22)O(3), the asymmetric unit has two independent molecules linked by a strong O-H...O hydrogen bond. The cyclohexane ring is trans fused to the cyclopentane ring bridged through an ethyl moiety. The hydroxyl groups act as donors as well as acceptors, resulting in an extensive two-dimensional hydrogen-bonded network in the (011) plane. Intermolecular O-H...O bonds between centrosymmetrically related molecules form a four-membered supramolecular assembly, leading to infinite chains parallel to the [011] direction, crosslinked in the [100] direction.
Journal Article↗
Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events.
Selective cyclooxygenase-2 (COX-2) inhibitors were developed as a response to the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents (NSAIDs). However, COX-2 inhibitors decrease vascular prostacyclin (PGI(2)) production and may disrupt the homeostatic mechanisms that limit the effects of platelet activation. Basic and clinical data raise concerns about a potential prothrombotic effect of this class of drugs. The widespread popularity of these agents mandates their prospective evaluation in patients with cardiovascular diseases or who are at risk for cardiovascular events.
Animals↗
Percutaneous treatment for carotid stenosis.
Stroke is the leading cause of serious long-term disability in the United States. A substantial portion of strokes are caused by atherosclerotic carotid artery disease. The conventional risk factors for coronary atherosclerosis are also responsible for carotid atherosclerosis. Carotid stenosis is encountered in medical practice in either symptomatic or asymptomatic states. In symptomatic patients, medical management with antiplatelet agents does not provide adequate protection against stroke. Carotid endarterectomy can help reduce the risk of a subsequent stroke. Asymptomatic patients with severe carotid stenosis can also benefit from surgical intervention if endarterectomy can be performed at a low operative risk. In recent years, percutaneous carotid stenting using self-expanding stents has become popular for the treatment of carotid stenosis. Although this initial experience has been reported from a high-risk patient population, the results are encouraging, with acceptable periprocedural stroke rates. Moreover, emboli protection devices, modern adjuvant pharmacotherapy, and modern self-expanding stents were not utilized in these studies. With rapidly expanding technology and advances in interventional pharmacology, improvement of clinical outcome is likely. Table 3 summarizes current recommendations for carotid stenting based on a panel of cardiologists, radiologists, and vascular surgeons. At this stage, randomized trials to compare endarterectomy with carotid stenting are underway. Cautious optimism is necessary until the optimal equipment, emboli protection devices, and adjuvant pharmacotherapies are fully investigated. Until then, carotid stenting should be restricted to high-risk candidates for carotid endarterectomy, including patients with severe cardiac comorbidities, previous neck surgeries or radiation, restenosis after endarterectomy, or other technical contraindications for surgery.
Angioplasty↗
Carotid artery intimal-medial thickness: indicator of atherosclerotic burden and response to risk factor modification.
BACKGROUND: A number of studies have used B-mode ultrasound to measure carotid intimal-medial thickness as an indicator of the severity of carotid atherosclerosis. METHODS: We reviewed the available data on carotid intimal-medial thickness in defining severity of atherosclerosis, with the use of high-quality studies that addressed clinical end points. RESULTS: Data from multiple studies demonstrate a high degree of reproducibility in measurements of intimal-medial thickness. A number of agents that include 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, angiotensin-converting enzyme inhibitors, and insulin sensitizers reduce carotid intimal-medial thickness and cardiovascular events, such as myocardial infarction and stroke. CONCLUSIONS: In this review article, various methods of measuring carotid intimal-medial thickness are examined and critiqued. In addition, the effects of various lifestyle modifications and therapeutic agents on intimal-medial thickness and cardiovascular end points are evaluated.
Anticholesteremic Agents↗
Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).
BACKGROUND: Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors. METHODS: In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B. RESULTS: Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57-0.79, P <.001). There were no significant differences in death/MI/SRI at 30 days (P =.465), death/MI at 30 days (P =.264), and stroke at 30 days with the type of heparin use (P =.201) after propensity risk adjustment. CONCLUSIONS: In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome.
Acetates↗
Coronary revascularization prior to elective vascular surgery: does it reduce cardiac risk?
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Angioplasty, Balloon, Coronary↗
Gene therapy in cardiovascular diseases.
Established modalities of treatment for obstructive coronary artery disease include medical therapy, bypass surgery and percutaneous coronary intervention. Similarly, conventional treatment of congestive heart failure is also limited to medical therapy, temporary assist devices and transplantation. A significant subset of patients with severe symptomatic coronary artery disease and end stage heart failure is not eligible for these traditional methods of treatment. In spite of maximal medical and revascularization therapy, these patients may not get adequate symptomatic benefit. After a decade of investigations, gene therapy has emerged as a promising therapeutic option for this group of patients. This review discusses newer modalities of therapy for this subset, including therapeutic angiogenesis with growth factors and cell transplantation.
Cardiovascular Diseases↗
Endovascular treatment of carotid artery aneurysms with stent grafts.
Two patients with cervical carotid artery aneurysms were treated with stent grafts. Case report #1 was a 65-year-old male with aneurysm of the right internal carotid artery and recurrent transient ischemic attacks. Case report #2 describes a 64-year-old male with a pulsatile neck mass and persistent neck discomfort. Both patients underwent successful implantation of stent grafts with complete obliteration of the aneurysms and alleviation of symptoms. Case report #2 also underwent coil embolization of the right external carotid artery to prevent retrograde filling of the aneurysmal sac. Endovascular stent graft obliteration of carotid aneurysms appears safe, feasible and a less invasive option compared to surgical repair.
Aged↗
Lack of cardioprotective effect of naproxen.
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Anti-Inflammatory Agents, Non-Steroidal↗