Conclusion This study demonstrates that high on treatment platelet reactivity with aspirin and/or clopidogrel is common amongst patients who develop stent thrombosis. Additionally this resistance can be improved with doubling the prior dose of antiplatelet therapy.
Full Answer
What is the prevalence of early stent thrombosis?
Aug 01, 2011 · The percentage patients with high post treatment platelet reactivity of both ST and control groups is depicted in Table 3. High post-clopidogrel platelet reactivity as defined as PRU ≥ 235 was present in 68.8% of patients with ST and 2.5% of controls (p = <0.001). There were two patients with high post-aspirin platelet reactivity in the ST group versus zero in the control …
Is more platelet reactivity better in stroke-prone patients?
May 17, 2011 · High post aspirin and/or clopidogrel platelet reactivity was significantly more common in patients with ST versus controls (75% vs. 2.5%, p = < 0.001). Overall, ST patients were younger (52.8 ± 10.5 vs. 59 ± 9.6 years; p = 0.039), had more pre-existing coronary artery disease (75% vs. 42%; p = 0.028) and smaller reference vessel diameters (2.9 ± 0.36 vs. 3.2 ± 0.54 mm; …
Is neoatherosclerotic change a common pathway for late stent failure?
We describe, to the best of our knowledge, the first incidence of stent thrombosis in a patient treated with ticagrelor, who exhibited high on-treatment platelet reactivity (HTPR) according to platelet reactivity testing. He was on clopidrogel and tested for platelet reactivity using the VerifyNow P2Y12 assay.
Should patients with high platelet pressure be switched from clopidogrel to prasugrel?
High on treatment platelet reactivity (HPR) is a common finding in subjects who develop stent thrombosis [6]. HPR has been shown to be an independent risk factor for …
What does increased platelet reactivity mean?
How common is late stent thrombosis?
Which of the following is the strongest predictor of stent thrombosis?
What is high residual platelet reactivity?
Does aspirin prevent stent thrombosis?
What is the cause of stent thrombosis?
When does in stent thrombosis happen?
What are the disadvantages of stents?
What is the remaining long term issue associated with drug eluting stents?
What is on treatment platelet reactivity?
What is platelet reactivity unit?
What is a BRS stent?
Bioresorbable stents (BRS) are an important technological development with potential to enhance the outcomes of patients treated by PCI and radically change future stenting practices. The basic concept is based upon the degradation of the stent backbone to inert particles after its useful function is served; once the stent has been fully degraded, this theoretically removes the risks associated with both ST and restenosis. Moreover, these devices offer additional potential benefits, including restoration of normal vasomotor tone of the stented segment and increase in lumen calibre due to positive vessel remodelling associated with stent degradation. This might in turn translate into improvements in coronary physiology and reduction in angina symptom burden. 14
What are the risk factors for restenosis after DES?
Early studies in the DES era showed that the major risk factors for restenosis after DES were vessel size, final diameter stenosis, and type of DES (i.e. SES were more effective in preventing ISR than paclitaxel-eluting stent). 90 By reducing the extent of injury at the time of implantation thinner stent struts are also associated with a reduced restenotic risk in comparison with thicker struts. 91 In the largest analysis to date, we investigated the risk factors for restenosis in a series of 10 004 patients with angiographic follow-up after coronary stenting. 81 Binary restenosis was detected in 26% of patients overall. At multivariate analysis, smaller vessel size (odds ratio 1.59 [95% confidence interval, 1.52–1.68] for each 0.5-mm decrease), total stented length (1.27 [1.21–1.33]), complex lesion morphology (1.35 [1.20–1.51]), diabetes mellitus (1.32 [1.19–1.46]), and history of bypass surgery (1.38 [1.20–1.58]) were independently associated with restenosis. Moreover, use of first-generation DES vs. bare metal stents (0.35 [0.31–0.39]) and second-generation DES vs. first-generation DES (0.67 [0.58–0.77]) were independent predictors of lower rates of restenosis. Overall in terms of therapeutic measures to reduce restenosis, the most important issues are likely to be meticulous attention to procedural detail and use of high-performance DES. Other approaches including systemic pharmacotherapy have been associated with mixed results and are discussed in detail elsewhere. 92
What is a clinical restenotic event?
The term clinical restenosis is sometimes used to refer to restenosis of the treated lesion accompanied by requirement for re-treatment , for example, due to symptoms or signs of ischaemia. Rates of clinical restenosis are usually considerably lower than rates of restenosis detected by imaging as not all restenotic lesions cause ischaemia or elicit symptoms.
What causes restenosis after PCI?
The higher degree of vessel injury with stent implantation in comparison with balloon angioplasty alone increased the extent of neointimal hyperplasia in the intervened segment and this is the dominant cause of restenosis after bare metal stent implantation. 13 Restenosis after PCI has been characterized as a distinct pathophysiological process rather than merely an accelerated form of post-intervention atherosclerosis. 76 In general, terms inflammatory response to vessel wall injury during PCI plays a central role in restenosis after stenting with vessel wall inflammation driving fibroblast growth and smooth muscle cell hyperplasia. Mechanistically contributing factors to restenosis after vascular intervention may be divided into five categories: (i) acute or subacute prolapse of the disrupted plaque, (ii) elastic recoil of the vessel wall, (iii) constrictive remodelling, (iv) neointimal hyperplasia (due to extracellular matrix deposition and smooth muscle cell hyperplasia), and (v) de novo in-stent atherosclerosis (neoatherosclerosis). 77
How long does neointimal formation last after stenting?
Angiographic surveillance studies have shown that neointimal formation after bare metal stenting tends to peak at 6 months after stenting and thereafter remain stable or regress somewhat over the medium term. 12, 83 This is in keeping with completion of vessel healing, contraction of neointima, and positive remodelling of the vessel wall. Interestingly, more prolonged follow-up of series out to 7–11 and 15–20 years indicated some further luminal re-narrowing beyond 4 years. 84, 85 After DES implantation however, the time course of restenosis seems to be rather different. In a large serial angiographic follow-up registry, we found that ongoing erosion of luminal calibre between 6 and 8 months and 2 years post-stenting is a feature of DES therapy. 46 Räber et al. showed incremental late loss in patients treated with first-generation DES who had surveillance angiography at 6–8 months and 5 years. 86 The observation of ongoing delayed late loss with DES beyond the 6- to 8-month time window supports the hypothesis of DES-associated delayed arterial healing seen in autopsy and preclinical studies and suggest that the temporal course of restenosis with DES may be significantly right-shifted compared with bare metal stents. Moreover, some of this late erosion of luminal calibre may be attributable to the higher incidence of in-stent neoatherosclerosis formation in DES. 48
What are the causes of stent failure?
Indeed, coupled with the reducing costs of these devices in most countries there remain very few indications where patients should be denied treatment with standard-of-care DES therapy. The two major causes of stent failure are stent thrombosis (ST) and in-stent restenosis (ISR). The incidence of both has reduced considerably in recent years. Current clinical registries and randomized trials with broad inclusion criteria show rates of ST at or <1% after 1 year and ∼0.2–0.4% per year thereafter; rates of clinical ISR are 5% respectively. Angiographic surveillance studies in large cohorts show rates of angiographic ISR of ∼10% with new-generation DES. The advent of high-resolution intracoronary imaging has shown that in many cases of late stent failure neoatherosclerotic change within the stented segment represents a final common pathway for both thrombotic and restenotic events. In future, a better understanding of the pathogenesis of this process may translate into improved late outcomes. Moreover, the predominance of non-stent-related disease as a cause of subsequent myocardial infarction during follow-up highlights the importance of lifestyle and pharmacological interventions targeted at modification of the underlying disease process. Finally, although recent developments focus on strategies which circumvent the need for chronically indwelling stents—such as drug-coated balloons or fully bioresorbable stents—more data are needed before the wider use of these therapies can be advocated.
How long after a stent implantation can you die?
Unexplained deaths within 30 days after the procedure or acute myocardial infarction involving the target-vessel territory without angiographic confirmation. Possible ST. All unexplained deaths occurring at least 30 days after the procedure. Timing of ST in relation to index stent implantation.
Why are RCTs not used in antiplatelet therapy?
A likely explanation for the failure of RCTs to demonstrate an advantage of laboratory monitoring of antiplatelet therapy rests on the lability of the platelet reactivity phenotype and/or the imprecision of platelet function tests in identifying the phenotype of each individual patient. It has been shown that, of 380 patients with high on-treatment platelet reactivity before PCI, 217 (57%) only displayed the same phenotype at 1 month, when platelet function studies had been repeated. 242 If this change is biologically plausible because the intestinal absorption of the drug during the acute phase may be less efficient than at later times, changes of the platelet reactivity phenotype in the opposite direction are more difficult to interpret. Indeed, among the 223 patients without HPR before PCI, only 176 (79%) displayed the same phenotype at 1 month; moreover, many patients changed categories twice in the two determinations of PR after PCI (at discharge and after 1 month). 242 Based on the negative results of all the published large randomized trials, international guidelines now recommend against laboratory monitoring of antiplatelet therapy. 254
What is standardization of preanalytical conditions?
These include the time of day at which blood samples should be taken (because platelet function follows a circadian rhythm), the time elapsed since the onset of the ACS and since the last intake of the drug, and the number of times the test should be repeated during follow-up.
How many SNPs are associated with platelet aggregation?
The first GWAS reported for platelet reactivity tested association of 2.5 million SNPs with platelet aggregation responses to ADP, collagen, and epinephrine.109 The primary cohorts were generally healthy, European-ancestry populations from the FHS (n=2,753) and the GeneSTAR cohorts (GS; n=1,238). SNPs at seven loci ( PEAR1, MRVI1, SHH, ADRA2A, PIK3CG, JMJD1C, and GP6; Fig. 4-3A) met genome-wide statistical significance and were replicated in an African-ancestry GS cohort ( n =840).
Is Clopidogrel a P2Y 12 antagonist?
It is important to emphasize that, despite the uncertainties that persist as to the association between genetic variables and the pharmacodynamic and clinical response to clopidogre l, a recent trial demonstrated the advantage of choosing among three P2Y 12 antagonists (clopidogrel , prasugrel and ticagrelor) based on genetic testing for CYP isoforms and ABCB1, in terms of reduction of both ischemic and bleeding events in patients with ACS. 236
Does Clopidogrel affect stent thrombosis?
The association between poor clinical outcomes of patients on treatment with clopidogrel and the presence of mutations of CYP has been demonstrated in observational and intervention studies. However, in contrast with the results of three metaanalyses, which included the early published studies and demonstrated an increased risk of MACE and, particularly, of stent thrombosis in carriers of either 1 or 2 mutated CYP2C19*2 alleles, 108–110 three metaanalyses did not indicate a substantial or consistent influence of loss-of-function CYP2C19 gene polymorphisms on the clinical efficacy of clopidogrel. 111–113 The different results of these last metaanalyses are likely due to the fact that they included studies published after the year 2010 (which showed weaker effects compared to the previous ones) and/or extracted only data of prespecified clinical events that conformed to unbiased and standardized definitions. Moreover, the question remains open as to whether the association that was found in some studies is explained by impaired clopidogrel metabolism by carriers of the mutation, or by pleiotropic effects, with negative impact on cardiovascular outcomes, independently of the administration of clopidogrel. 114 In 2016, a substudy of the TRILOGY-ACS trial showed that, in 5736 medically managed ACS patients treated with clopidogrel or prasugrel, CYP2C19 metabolizer status was not associated with the composite outcome of cardiovascular death, MI, or stroke. 220 In patients treated with clopidogrel, ABCB1 3435C → T genotype was significantly associated with the risk of cardiovascular death, MI, or stroke in the TRITON TIMI-38 trial, which compared clopidogrel and prasugrel in patients with ACSs undergoing PCI. 115
Does Clopidogrel inhibit platelet function?
A significant proportion of subjects (about 1/3) treated with clopidogrel are very poor responders, displaying almost no inhibition of platelet function. 101,102 Several lines of evidence strongly suggest that variability in active metabolite generation is the primary explanation for clopidogrel antiplatelet response variability. 101,102 Loss of function mutations ( e.g., CYP2C19*2) and gain of function mutations ( e.g., CYP2C19*17) of CYP isoforms are associated with variable degrees of production of the active metabolite and, hence, of the pharmacodynamic response to the drug. 101,102
Is clopidogrel a cytochrome isoform?
Clopidogrel resistance and clopidogrel HOPR are relatively common and can be mediated by a range of factors , including cytochrome isoform polymorphisms (CYP2C19∗2 allele is associated with poor response due to poor conversion of the pro-drug to the active form), inadequate absorption, drug interactions, and disease states. When LTA and WBA are performed on samples from patients treated with P2Y12 antagonists, ADP-induced aggregation is expected to be reduced. Unfortunately, there is up to an 80% overlap between treated and untreated patients in these assays. This is likely due to the effect of ADP on P2Y1 and the relatively low precision of the assay. Thus, the cutoff values for the detection of HOPR by aggregation are not clear. PFA-100 is relatively insensitive to these agents and should not be used to detect resistance. A newer PFA-200 P2Y cartridge has been developed and shows better sensitivity, but its performance characteristics are unclear at present. The VerifyNow P2Y12 cartridge is relatively specific but may be influenced by simultaneous presence of GPIIb/IIIA inhibitors and platelet counts outside the validated range of 119,000–502,000/μL. The performance characteristics of the new iteration of the assay that is solely based on PRU values are not clear at present. VASP is considered a gold standard for detecting true resistance but is expensive and requires technical expertise.
