Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis.
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SUBMITTER: Lohaus R
PROVIDER: S-EPMC5021963 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients.ObjectivesThe aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus ≤12 months after PCI on very late outcomes in patients with diabetes mellitus (DM).MethodsUsing the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, ≤4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI).ResultsIn patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents.ConclusionsExtending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES.
| S-EPMC4578293 | biostudies-literature
Project description:PurposeData regarding vessel healing by optical coherence tomography (OCT) after everolimus-eluting bioresorbable scaffolds (BRS) or everolimus-eluting metallic stent (EES) implantation in acute myocardial infarction (AMI) patients is scarce. We compared OCT findings after BRS or EES implantation in patients with AMI enrolled in a randomized trial.MethodsIn ISAR-Absorb MI, AMI patients were randomized to BRS or EES implantation, with 6-8 month angiographic follow-up. This analysis includes patients who underwent OCT during surveillance angiography. Tissue characterization was done using grey-scale signal intensity analysis. The association between OCT findings and target lesion failure (TLF) at 2 years was investigated.ResultsOCT was analyzed in 103 patients (2237 frames, 19,827 struts) at a median of 216 days post-implantation. Of these, 70 were treated with BRS versus 32 with EES. Pre-(92.8 vs. 68.7%, p = 0.002) and post-dilation (51.4 vs. 12.5%, p < 0.001) were more common in BRS as compared to EES. Strut coverage was higher in BRS vs. EES (97.5% vs. 90.9%, p < 0.001). Mean neointimal thickness was comparable in both groups [85.5 (61.9, 124.1) vs. 69.5 (32.7, 127.5) µm, respectively, p = 0.20]. Mature neointimal regions were numerically more common in BRS (43.0% vs. 24.6%; p = 0.35); this difference was statistically significant in ST-elevation myocardial infarction patients (40.9% vs. 21.1%, p = 0.03). At two-years, 8 (7.8%) patients experienced TLF. Mean neointimal area [0.61 (0.21, 1.33) vs. 0.41 (0.11, 0.75) mm2, p = 0.03] and mean neointimal coverage [106.1 (65.2, 214.8) vs. 80.5 (53.5, 122.1) µm, p < 0.01] were higher, with comparable tissue maturity, in lesions with versus without TLF.ConclusionsIn selected patients who underwent OCT surveillance 6-8 months after coronary intervention for AMI with differing implantation characteristics depending on the device type used, vessel healing was more advanced in BRS compared with EES, particularly in the STEMI subgroup.
| S-EPMC8494721 | biostudies-literature
Project description:Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).
| S-EPMC4481318 | biostudies-literature
Project description:Patients undergoing coronary artery stenting receive an antiplatelet regimen to reduce the risk of antithrombotic complications. Current guidelines recommend the use of acetyl salicylic acid (aspirin) and clopidogrel as evidenced by large clinical trials. There has been a concern about variable responses of patients to aspirin and clopidogrel which may predispose them to subacute stent thrombosis or late stent thrombosis. Up to 25% of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) were found to have hyporesponsiveness or resistance to clopidogrel which may predispose them to recurrent events. Dual antiplatelet regimen is a standard therapy in these patients and there is always a concern about variable responses to aspirin and clopidogrel predisposing them to acute coronary syndrome (ACS). Prevalence of this hyporesponsiveness or resistance may be due to noncompliance, genetic mutations, co-morbid situations and concomitant use of other drugs. This issue is of considerable importance in the era of coronary drug eluting stents when a long-term dual antiplatelet regimen is needed. This paper is a review for clinicians taking care of such patients with hyporesponsiveness or nonresponsiveness to dual antiplatelet regimen.
| S-EPMC2788601 | biostudies-other
Project description:"Partners in Dementia Care" (PDC) tested the effectiveness of a care-coordination program integrating healthcare and community services and supporting veterans with dementia and their caregivers. Delivered via partnerships between Veterans Affairs medical centers and Alzheimer's Association chapters, PDC targeted both patients and caregivers, distinguishing it from many non-pharmacological interventions. Hypotheses posited PDC would improve five veteran self-reported outcomes: 1) unmet need, 2) embarrassment about memory problems, 3) isolation, 4) relationship strain and 5) depression. Greater impact was expected for more impaired veterans. A unique feature was self-reported research data collected from veterans with dementia.Five matched communities were study sites. Two randomly selected sites received PDC for 12 months; comparison sites received usual care. Three structured telephone interviews were completed every 6 months with veterans who could participate.Of 508 consenting veterans, 333 (65.6%) completed baseline interviews. Among those who completed baseline interviews, 263 (79.0%) completed 6-month follow-ups and 194 (58.3%) completed 12-month follow-ups. Regression analyses showed PDC veterans had significantly less adverse outcomes than those receiving usual care, particularly for more impaired veterans after 6 months, including reduced relationship strain (B = -0.09; p = 0.05), depression (B = -0.10; p = 0.03), and unmet need (B = -0.28; p = 0.02; and B = -0.52; p = 0.08). PDC veterans also had less embarrassment about memory problems (B = -0.24; p = 0.08). At 12 months, more impaired veterans had further reductions in unmet need (B = -0.96; p < 0.01) and embarrassment (B = -0.05; p = 0.02). Limitations included use of matched comparison sites rather than within-site randomization and lack of consideration for variation within the PDC group in amounts and types of assistance provided.Partnerships between community and health organizations have the potential to meet the dementia-related needs and improve the psychosocial functioning of persons with dementia.NCT00291161.
| S-EPMC3978714 | biostudies-other
Project description:ObjectivesPatients with chronic kidney disease (CKD) are at high risk of death or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We assessed whether prolonged dual antiplatelet therapy beyond the recommended 12 months may prevent adverse outcomes in patients with CKD receiving drug-eluting stents (DES) or bare-metal stents (BMS).MethodsWe studied all Veterans receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA) Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular filtration rate <60 mL/min) or normal renal function. We used landmark analyses from 12 months after PCI with Cox proportional hazards multivariable and propensity-adjusted models to assess the effect of prolonged clopidogrel (more than 12 months) versus 12 months or less after PCI on clinical outcomes from 1 year to 4 years after PCI.ResultsOf 23 042 eligible subjects receiving PCI, 4880 (21%) had CKD. Compared with normal renal function, patients with CKD had higher risks of death or MI 1-4 years after DES (21% vs 12%, HR=1.75; 95% CI 1.51 to 2.04) or BMS (28% vs 15%, HR=2.10; 95% CI 1.90 to 2.32). In patients with CKD receiving DES, clopidogrel use of more than 12 months after PCI was associated with lower risks of death or MI (18% vs 24%, HR=0.74; 95% CI 0.58 to 0.95), and death (15% vs 23%, HR=0.61; 95% CI 0.47 to 0.80), but had no effect on repeat revascularisation 1-4 years after PCI.ConclusionsIn patients with CKD, prolonging clopidogrel beyond 12 months after PCI may decrease the risk of death or MI only in patients receiving first-generation DES. These results support a patient-tailored approach to prolonging clopidogrel after PCI.
| S-EPMC4580134 | biostudies-literature
Project description:BackgroundClopidogrel use after drug-eluting stent (DES) coronary artery implantation is essential for the prevention of early in-stent thrombosis, but clopidogrel use among older DES recipients has not been widely studied. We sought to identify characteristics associated with failure to fill a clopidogrel prescription and to examine the relationship between a clopidogrel prescription fill and hospitalization for acute myocardial infarction (AMI) or death.Methods and resultsThis study was a retrospective analysis of administrative data (20% sample) of 15 996 Medicare Part D enrollees who received a DES in 2006 to 2007. We modeled the adjusted probability and odds of clopidogrel prescription fill within 7 and 90 days of discharge and its association with AMI hospitalization or death. Of the study sample, 19.7% did not fill a clopidogrel prescription within 7 days of discharge, falling to 13.3% by day 90. The adjusted probability of filling a clopidogrel prescription within 7 or 90 days of discharge was lower for patients with dementia (20.2% less likely; 95% CI, 10.4%-30.1%), depression (10.7% less likely; 95% CI, 6.9%-14.5%), age >84 years compared to age 65 to 69 years (10.6% less likely; 95% CI, 8.6%-12.7%), black race (6.6% less likely; 95% CI, 4.2%-9.0%), intermediate levels of medication cost share (5.2% less likely; 95% CI, 2.9%-7.6%), and female sex (3.3% less likely; 95% CI, 2.1%-4.5%). It was higher for patients initially hospitalized for an AMI (12.5% more likely; 95% CI, 11.3%-13.6%). Failure to fill a clopidogrel prescription within 7 days of discharge was associated with a higher adjusted odds ratio of death during days 8 to 90 (2.44; 95% CI, 1.76-3.38) but was not associated with an increased risk of hospitalization for AMI.ConclusionsOne in 5 patients failed to fill a prescription for clopidogrel at 7 days after DES placement, and 1 in 7 failed to do so by 3 months. Individual characteristics available at the time of hospital discharge were associated with a clopidogrel prescription fill. Those characteristics most strongly associated with nonadherence, including age >84 years, not having an AMI, depression, and dementia, may guide clinicians and health systems seeking to target this high-risk population and improve health outcomes after percutaneous coronary intervention.
| S-EPMC3261311 | biostudies-literature
Project description:BackgroundThe treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is challenging as it has a high risk of recurrence.AimsThe aim of this analysis was to develop and validate a model to predict the risk of repeat percutaneous coronary intervention (PCI) for recurrent DES-ISR.MethodsA retrospective, observational analysis was performed including consecutive patients treated with PCI for DES-ISR at two centres in Germany. Included patients were randomly divided into training and validation cohorts. Two regression analyses identified factors associated with repeat PCI for recurrent DES-ISR up to 1 year. The discriminative ability of the resultant model was then compared to a benchmark ISR classification model using bootstrap resampling. A classification and regression tree analysis and a numerical scoring system (the ISAR score) were used to predict the risk of repeat PCI for recurrent DES-ISR based on the identified predictors.ResultsWe included 1,986 patients in the current analysis, divided randomly into training (1,471 patients, 1,778 lesions) and validation (515 patients, 614 lesions) cohorts. Four factor variables (a non-focal ISR pattern, a time interval to ISR of <6 months, ISR of the left circumflex artery and ISR in a calcified vessel) were associated with repeat PCI for recurrent DES-ISR at 1-year follow-up. On bootstrap resampling analysis, the C-statistic for the model including these four variables was 0.60 (95% confidence interval [CI]: 0.57-0.63), whereas the C-statistic for the benchmark ISR classification model was 0.54 (95% CI: 0.52-0.57), a difference that was statistically significant (delta C-statistic 0.062; 95% CI: 0.035-0.094; p<0.001). The cumulative incidence of repeat PCI for recurrent DES-ISR was over three times higher in DES-ISR lesions with an ISAR score of ≥3 in comparison to lesions with an ISAR score of 0.ConclusionsThis study developed and validated a risk prediction model for repeat PCI for recurrent DES-ISR at 1-year follow-up. This model served to generate the ISAR score, a standardised tool that can be used to predict the 1-year risk of repeat PCI for recurrent DES-ISR.
| S-EPMC10068863 | biostudies-literature
Project description:BackgroundVery long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus.MethodsWe investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years.ResultsThis analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73-1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88-1.11; P = 0.88).ConclusionAt 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time.Trial registrationClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).
| S-EPMC8484170 | biostudies-literature
Project description:We previously found higher level of endothelial cell (EC) activation in patients who suffered from in-stent restenosis after bare-metal stenting compared to subjects who underwent drug-eluting stenting (DES) showing no complications. Here we investigated the potential transcriptional and post-transcriptional regulatory mechanisms by which everolimus attenuated EC activation after DES. We studied the effect of everolimus on E-selectin (SELE) and VCAM1 mRNA levels when human coronary artery (HCAECs) and human umbilical vein ECs were challenged with recombinant TNF-α (100 ng/mL) for 1-24 hours in the presence or absence of everolimus using 0.5 μM concentration locally maintained by DES. EC activation was evaluated via the levels of IL-1β and IL-6 mRNAs with miR-155 expression by RT-qPCR as well as the nuclear translocation of nuclear factor kappa beta (NF-κB) detected by fluorescence microscopy. To investigate the transcriptional regulation of E-selectin and VCAM-1, TNF-α-induced enhancer RNA (eRNA) expression at p65-bound enhancers in the neighboring genomic regions of SELE and VCAM1 genes, including SELE_-11Kb and VCAM1_-10Kb, were measured in HCAECs. Mature and precursor levels of E-selectin and VCAM-1 repressor miR-181b were quantified to analyze the post-transcriptional regulation of these genes in HCAECs. Circulating miR-181b was analyzed in plasma samples of stented subjects by stem-loop RT-qPCR. TNF-α highly elevated E-selectin and VCAM-1 expression at transcriptional level in ECs. Levels of mature, pre- and pri-miR-181b were repressed in ECs by TNF-α, while everolimus acted as a negative regulator of EC activation via inhibited translocation of NF-κB p65 subunit into cell nuclei, lowered eRNA expression at SELE and VCAM1 genes-associated enhancers and modulated expression of their post-transcriptional repressor miR-181b. Significant negative correlation was observed between plasma miR-181b and soluble E-selectin and VCAM-1 in patients. In conclusion, everolimus attenuates EC activation via reduced NF-κB p65 translocation causing decreased E-selectin and VCAM-1 expression at transcriptional and post-transcriptional level after DES.
| S-EPMC5995375 | biostudies-literature