Biomedical subjects

Paul A Gurbel

Publications and source records attributed to Paul A Gurbel.

At least 19 recordsLinked to original sources

PubMed2026

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (≤1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: ≤1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: ≥2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while ≤1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans↗

PubMed2006

Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study.

OBJECTIVES: This study was performed to compare the effects of antiplatelet regimens on early inflammation and cardiac marker release after elective stenting. BACKGROUND: Few data exist regarding the comparative effects of specific antiplatelet regimens on early inflammation marker release after stenting. METHODS: In a 2 x 2 factorial randomized investigation, patients undergoing stenting were treated with either clopidogrel alone (300 mg or 600 mg; n = 60) or clopidogrel with eptifibatide (n = 60). Platelet aggregation (5 and 20 muM adenosine diphosphate [ADP]), ADP-stimulated expression of active glycoprotein (GP) IIb/IIIa, and platelet-bound P-selectin, tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), and cardiac markers were measured. RESULTS: Compared with a strategy of clopidogrel alone, clopidogrel + eptifibatide reduced the release of cardiac markers. A marked reduction in platelet aggregation and active GP IIb/IIIa expression (p < or = 0.001) with clopidogrel + eptifibatide was associated with a decrease in CRP and TNF-alpha release (p < or = 0.001). CONCLUSIONS: A strategy of clopidogrel with GP IIb/IIIa blockade resulted in superior inhibition of inflammation and cardiac marker release, which was accompanied by superior platelet inhibition immediately after percutaneous coronary intervention compared with a strategy of clopidogrel alone. The mechanistic and clinical implications of attenuated periprocedural inflammation and myocardial necrosis with a strategy of GP IIb/IIIa inhibition warrant further investigation.

Aged↗

PubMed2006

Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial.

OBJECTIVES: This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES). BACKGROUND: Whether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined. METHODS: A prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14 mm and < or =27 mm. The primary end point was 8-month angiographic in-segment late lumen loss. RESULTS: Angiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 +/- 0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly. CONCLUSIONS: Compared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).

Aged↗

PubMed2006

Clopidogrel resistance?

Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y(12) receptor. Combination antiplatelet therapy with clopidogrel and aspirin is an important strategy for patients with acute coronary syndromes and those undergoing percutaneous interventions. Despite significant benefits demonstrated with combination antiplatelet treatment in large clinical trials, the occurrence of adverse ischemic events, including stent thrombosis, remains a serious clinical problem. Recent studies have demonstrated distinct response variability and nonresponsiveness to clopidogrel therapy based on ex vivo platelet function measurements. Small scale investigations have suggested that nonresponsiveness may be associated with a heightened risk for adverse clinical events. The above findings have stimulated a close examination of clopidogrel metabolism.

Aspirin↗

PubMed2006

Antiplatelet drug resistance and drug-drug interactions: Role of cytochrome P450 3A4.

Antiplatelet therapy provided pivotal advances in the treatment of cardiovascular disease. Aspirin and thienopyridine, clopidogrel, is currently the treatment of choice in acute coronary syndromes and the prevention of thrombosis after coronary stent implantation. Despite the efficacy of this dual antiplatelet therapy in reduction of adverse coronary events in patients with acute coronary syndromes, complications persist in a subgroup of these patients. Emerging causes of aspirin and clopidogrel resistance may translate to increase risk for recurrent myocardial infarction, stroke, or cardiac related mortality. However, the mechanism of antiplatelet drug resistance remains incompletely characterized, and a sensitive and specific assay of aspirin and clopidogrel effect that reliably predicts treatment failure has not emerged. To date, evidence supporting antiplatelet drug resistance are pharmacokinetic response variability, drug-drug interaction through competitive inhibition a specific enzymatic pathway, genetic variability, and variability in the induction of enzymatic pathway in metabolic activation of prodrugs, like clopidogrel. Further investigation or guidelines are needed to optimize antiplatelet treatment strategies to identify and treat patients resistant to aspirin and/or clopidogrel.

Animals↗

PubMed2006

Delayed thrombin-induced platelet-fibrin clot generation by clopidogrel: a new dose-related effect demonstrated by thrombelastography in patients undergoing coronary artery stenting.

BACKGROUND: We have previously demonstrated that clopidogrel reduces platelet activation and aggregation in patients undergoing stenting. However, the effect of the clopidogrel loading dose on the rate of thrombin-induced platelet-fibrin clot formation is unknown in this patient population. METHODS AND RESULTS: Using thrombelastography (TEG) we measured the time to platelet-fibrin clot formation (R), a marker of the speed of thrombin generation, in 120 patients undergoing elective coronary artery stenting treated with standard and high loading doses of clopidogrel. Platelet reactivity to adenosine diphosphate (ADP) by light transmittance aggregometry (LTA) was determined simultaneously. Measurements were made immediately before and at 24 h after clopidogrel treatment. Clopidogrel produced a prolongation in R (4.4+/-1.4 min pre vs. 5.4+/-1.7 min post, p<0.001) that directly correlated with the change in platelet aggregation (r=0.65, p<0.0001). Prolongation in R was greatest in patients treated with a high loading dose (p=0.004). CONCLUSIONS: Delayed thrombin-induced platelet-fibrin clot formation as measured by TEG is a newly reported dose-related effect of clopidogrel that may contribute to the overall antithrombotic properties of the drug in patients undergoing stenting. This effect was more marked in patients loaded with 600 mg, lending further mechanistic support for this dose of clopidogrel as a more effective antithrombotic regimen than the standard 300 mg dose. Measurement of R may serve as a new indicator of clopidogrel responsiveness.

Aged↗

PubMed2006

Drug insight: Clopidogrel nonresponsiveness.

Platelet reactivity to agonists and subsequent activation are important factors that affect the development of atherothrombosis and resultant ischemic events. Pharmacologic intervention with clopidogrel and aspirin during acute coronary syndromes and percutaneous coronary intervention is considered the gold standard for attenuating platelet activation and aggregation. Despite significant benefits reported with dual antiplatelet treatment in major clinical trials, the occurrence of adverse ischemic events, including stent thrombosis, remains a serious clinical problem. Nonresponsiveness, also called resistance, to current clopidogrel regimens might play a part in the occurrence of ischemic events. Various mechanisms have been implicated in nonresponsiveness to clopidogrel, including variability in intestinal absorption and hepatic conversion to the active metabolite, drug-drug interactions and receptor polymorphisms. Increased loading and maintenance doses and the use of new and more-potent P2Y12-receptor blockers might overcome the phenomenon of clopidogrel nonresponsiveness. The aim of this article is to provide a comprehensive and current review of clopidogrel response variability and nonresponsiveness.

Clopidogrel↗

PubMed2006

Aspirin and clopidogrel resistance: consideration and management.

The efficacy with aspirin and clopidogrel treatment has been demonstrated in various clinical trials. Laboratory evaluation of platelet response in recent studies revealed that a distinctive response variability and nonresponsiveness/resistance in selected patients were associated with these antiplatelet agents. Moreover, some studies have correlated this nonresponsiveness/resistance phenomenon to the occurrence of thrombotic events. At this time there are no uniformly established methods to quantify exvivo platelet reactivity after clopidogrel and aspirin treatment of the extent of platelet inhibition by clopidogrel and aspirin. Therefore, specific treatment recommendations for patients exhibiting high platelet reactivity or poor platelet inhibition during clopidogrel or aspirin therapy are not established. A higher aspirin dose and strict compliance to therapy may overcome the occurrence of "aspirin resistance" in selected patients. A higher clopidogrel dose may be considered in patients exhibiting clopidogrel nonresponsiveness.

Adenosine↗

PubMed2006

Prasugrel.

Clinical trials have demonstrated the superior clinical efficacy of dual antiplatelet therapy with a thienopyridine (a P2Y(12) receptor blocker) and aspirin (COX-1 inhibitor) in patients undergoing stenting as well as patients with acute coronary syndromes. However, clopidogrel treatment is associated with a wide response variability and non-responsiveness in selected patients. The latter phenomenon is linked to the occurrence of recurrent ischaemic events including stent thrombosis in the recent studies. Prasugrel is a new thienopyridine derivative that produces more potent platelet inhibition and a rapid onset of action that is associated with irreversible P2Y(12) receptor blockade. The latter properties of prasugrel may provide a superior alternative to clopidogrel, with less response variability and a decreased prevalence of non-responsiveness.

Adenosine Diphosphate↗

PubMed2006

Clopidogrel resistance: implications for coronary stenting.

Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clopidogrel treatment. Preliminary data support the hypothesis that patients with reactive or clopidogrel nonresponsive platelets are at risk for thrombotic events. However, the magnitude of the clinical effect remains unknown and relationship between nonresponsiveness and risk of clinical events is under-investigated. Several important questions that must be answered are: A) What is the relation of clopidogrel resistance and high platelet reactivity to the occurrence of stent thrombosis, recurrent myocardial infarction, stroke and death?; B) Is there a threshold of platelet reactivity that correlates with the onset of thrombotic risk?; and C) What is the cost of administering clopidogrel to non-responsive patients? Finally, our understanding of the clinical relevance of drug resistance and high platelet reactivity should be facilitated by the use of validated point-of-service devices. The mechanisms of the response variability to clopidogrel remain incompletely defined. The contribution of intra- and extracellular pathways are under investigation.

Animals↗

PubMed2006

Clinical applications of antiplatelet therapy.

Dual antiplatelet therapy with aspirin and a thienopyridine has become the standard of care for patients undergoing percutaneous intervention with stenting, regardless of indication. This article will examine the evidence for and against the use of aspirin and thienopyridines, with emphasis on platelet resistance and nonresponsiveness. Data suggest that in some patients, clopidogrel plus aspirin is not superior to aspirin alone. Resistance to aspirin and clopidogrel has been reported. Patients exhibiting aspirin resistance, as measured by an elevated platelet aggregate ratio, have a 10-fold increase in the risk of recurrent vascular events as compared to aspirin-sensitive patients. Clopidogrel nonresponsiveness has been a consistently observed phenomenon in studies utilizing various P2Y12 receptor-specific assays. Nonresponsiveness to clopidogrel treatment has been suggested as a risk factor for the occurrence of ischemic events and stent thrombosis.

Angioplasty, Balloon, Coronary↗

PubMed2006

The relationship of platelet reactivity to the occurrence of post-stenting ischemic events: emergence of a new cardiovascular risk factor.

The reactivity of platelets to agonists plays a central role in the genesis of thrombosis following percutaneous coronary intervention (PCI) and spontaneous plaque rupture. Antiplatelet therapy has reduced the occurrence of thrombotic events following PCI, including myocardial infarction and stent thrombosis. Because the platelet is a fundamental component in the generation of an arterial thrombus and the stimulus for thrombosis is marked in PCI, it is logical to predict that patients with superior platelet inhibition would have the best outcomes with respect to ischemic events post PCI. However, until recently there was little information linking measurements of high ex vivo platelet reactivity to the occurrence of ischemic events. An emerging body of data, mostly from small studies, supports the pivotal link between periprocedural platelet physiology and increased risk of adverse thrombotic events. This review explores the available information linking platelet reactivity during and after PCI to the occurrence of adverse events, including myocardial infarction, recurrent ischemia within 6 months, and stent thrombosis.

Angioplasty, Balloon, Coronary↗

PubMed2005

Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level.

OBJECTIVES: This study sought to determine the effect of aggressive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low-density lipoprotein (LDL) concentrations. BACKGROUND: The effects of statins may well go beyond lipid lowering, and these pleiotropic effects may be of benefit in the treatment of heart failure. METHODS: Fifteen patients with NICM on standard maximized heart failure medication were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV) or matching placebo for a 12-week treatment period with a minimum of an 8-week washout period. The following surrogate markers were evaluated: N-terminal-pro brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha, circulating levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate variability. RESULTS: After ATV therapy, there was a significant decrease in LDL concentration from 110 +/- 27 mg/dl to 55 +/- 18 mg/dl (p < 0.05). There were no differences between ATV and placebo with regard to the surrogate markers measured. CONCLUSIONS: Based on these findings, it seems that the administration of high-dose statins to a heart failure population with modest LDL levels and no other indication for statin therapy was neither beneficial nor detrimental as determined by surrogate marker measures. Further studies are needed to determine whether there is an appropriate patient population and optimal dose (LDL concentration) for the treatment of systolic heart failure with statin therapy.

C-Reactive Protein↗

PubMed2005

Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study.

OBJECTIVES: We investigated the relation of high ex vivo platelet reactivity, rapid fibrin generation, and high thrombin-induced clot strength to postdischarge ischemic events in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: High platelet reactivity and rapid fibrin generation may affect the incidence of ischemic events after PCI. However, limited data is available to link these ex vivo markers to the occurrence of events. METHODS: We measured platelet reactivity to adenosine diphosphate (ADP) by light transmittance aggregometry (LTA) in patients undergoing PCI (n = 192). Clot strength, a measure of thrombin-induced fibrin and platelet interactions, and the time to initial fibrin generation, a marker of thrombin activity, were measured by thrombelastography. The relation of these measurements to ischemic event occurrence was prospectively examined over six months. RESULTS: A total of 100% and 84% of patients were on aspirin and clopidogrel therapy, respectively, at the time of the initial event. Posttreatment ADP-induced aggregation by LTA (63 +/- 12% vs. 56 +/- 15%, p = 0.02) and clot strength (MA) were higher (74 +/- 5 mm vs. 65 +/- 4 mm, p < 0.001) and time to initial fibrin generation was shorter (4.3 +/- 1.3 min vs. 5.9 +/- 1.5 min, p < 0.001) in patients with events (n = 38). The event rates in the highest quartiles of LTA and MA were 32% and 58%, respectively. CONCLUSIONS: High platelet reactivity and clot strength, and rapid fibrin formation are novel risk factors for ischemic events after PCI. Clot strength is more predictive than ADP-induced platelet aggregation and may explain the occurrence of events despite treatment with cyclooxygenase-1 and P2Y12 inhibitors.

Angioplasty, Balloon, Coronary↗

PubMed2005

Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study.

OBJECTIVES: We investigated whether patients who suffered subacute stent thrombosis (SAT) have higher post-treatment reactivity than those who do not encounter stent thrombosis. BACKGROUND: High post-treatment platelet reactivity has been reported after coronary stenting after clopidogrel therapy and may be an important factor in the occurrence of SAT. METHODS: We identified patients with SAT treated at two tertiary care centers over a 1.5-year period. Light transmittance aggregation induced by adenosine diphosphate (ADP) and arachidonic acid, total and activated glycoprotein (GP) IIb/IIIa after stimulation with ADP, and vasodilator-stimulated phosphoprotein phosphorylation levels to measure P2Y12 receptor inhibition were determined (n = 20) and compared with an age-matched group of patients without SAT (n = 100). High post-treatment platelet reactivity was defined as >75th percentile ADP-induced aggregation in the group without SAT. RESULTS: The SAT patients had higher mean platelet reactivity than those without SAT by all measurements (p < 0.05): 49 +/- 4% versus 33 +/- 2% for 5 micromol/l ADP-induced aggregation and 65 +/- 3% versus 51 +/- 2% for 20 micromol/l ADP-induced aggregation (p < 0.001), 69 +/- 5% versus 46 +/- 9% for P2Y12 reactivity ratio (p = 0.03), and 138 +/- 19 mean fluorescence intensity (MFI) versus 42 +/- 4 MFI for stimulated GP IIb/IIIa expression (p < 0.001). Of patients with SAT, 60% had high platelet reactivity. CONCLUSIONS: High post-treatment platelet reactivity and incomplete P2Y12 receptor inhibition are risk factors for SAT. Measures to uniformly determine platelet reactivity after coronary stenting and treatment strategies to improve P2Y12 receptor inhibition in patients with high post-treatment platelet reactivity should be further investigated.

Aged↗

PubMed2005

Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation.

OBJECTIVES: This study sought to determine the prevalence of platelet aspirin resistance using methods that directly indicate the degree of platelet cyclooxygenase inhibition. BACKGROUND: Aspirin resistance in platelets may be overestimated by nonspecific laboratory measurements that do not isolate cyclooxygenase activity. METHODS: Arachidonic acid (AA)-induced light-transmittance platelet aggregation (LTA) and thrombelastography (TEG) platelet mapping were performed on the blood of healthy subjects (n = 6) before and 24 h after receiving 325 mg aspirin, and on 223 patients reporting compliance with long-term daily aspirin treatment (n = 203 undergoing percutaneous intervention [PCI] and n = 20 with a history of stent thrombosis). Aspirin resistance was defined as >20% aggregation by LTA or >50% aggregation by TEG. RESULTS: In healthy subjects, AA-induced aggregation by LTA was 82 +/- 10% before and 2 +/- 1% at 24 h after aspirin (p < 0.001), and aggregation by TEG was 86 +/- 14% before and 5 +/- 7% at 24 h after aspirin (p < 0.001). In compliant patients, AA-induced aggregation by LTA was 3 +/- 2% before PCI and 3 +/- 2% after PCI (p = NS), and aggregation by TEG was 5 +/- 9% before PCI and 6 +/- 14% after PCI (p = NS). Seven PCI patients were noncompliant, and all were aspirin sensitive after in-hospital aspirin treatment. Among 223 patients, only one patient ( approximately 0.4%) was resistant to aspirin treatment. CONCLUSIONS: Platelet aspirin resistance assessed by methods that directly indicate inhibition of cyclooxygenase is rare in compliant patients with coronary artery disease.

Adult↗

PubMed2005

The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.

OBJECTIVES: We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA). BACKGROUND: We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA. METHODS: Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel. RESULTS: Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 microM ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR. CONCLUSIONS: A 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.

Adenosine Diphosphate↗

PubMed2005

Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetes mellitus: the TAXUS-IV trial.

OBJECTIVES: We sought to determine the safety and efficacy of polymer-regulated site-specific delivery of paclitaxel in patients with diabetes mellitus undergoing stent implantation. BACKGROUND: Percutaneous coronary intervention in patients with diabetes is associated with high rates of restenosis and repeat revascularization due to excessive neointimal proliferation, a process that may be blunted with the site-specific delivery of paclitaxel. METHODS: In the TAXUS-IV trial, 1,314 patients were prospectively randomized to the slow rate-release polymer-based paclitaxel-eluting TAXUS stent or the bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). Medically treated diabetes was present in 318 patients (24%), 105 of whom required insulin. RESULTS: Among patients with diabetes, the TAXUS stent, compared to the bare-metal stent, reduced the rate of 9-month binary angiographic restenosis by 81% (6.4% vs. 34.5%, p < 0.0001), and reduced the 12-month rates of target lesion revascularization by 65% (7.4% vs. 20.9%, p = 0.0008), target vessel revascularization by 53% (11.3% vs. 24%, p < 0.004), and composite major adverse cardiac events by 44% (15.6% vs. 27.7%, p = 0.01). The one-year rates of cardiac death (1.9% vs. 2.5%), myocardial infarction (3.2% vs. 6.4%), and subacute thrombosis (0.6% vs. 1.2%) were comparable between the paclitaxel-eluting and control stents, respectively. In the insulin-requiring subgroup, the TAXUS stent reduced angiographic restenosis by 82% (7.7% vs. 42.9%, p = 0.0065), and reduced the one-year rate of target lesion revascularization by 68% (6.2% vs. 19.4%, p = 0.07), a relative reduction similar to patients without diabetes. CONCLUSIONS: The site-specific delivery of paclitaxel after coronary stent implantation is highly effective in reducing clinical and angiographic restenosis in patients with diabetes mellitus.

Antineoplastic Agents↗