Gabriel Sardi

Incidence and predictors of coronary stent thrombosis: Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses

BACKGROUND Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis. METHODS PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥ 2000 patients undergoing stenting or reporting on ≥ 25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised. RESULTS A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22 months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently. CONCLUSIONS Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

Comparison between Society of Thoracic Surgeons Score and logistic EuroSCORE for predicting mortality in patients referred for transcatheter aortic valve implantation

BACKGROUND The primary inclusion criteria from both the Society of Thoracic Surgeons (STS) score and the logistic EuroSCORE are currently used to identify high-risk and inoperable patients eligible for transcatheter aortic valve implantation (TAVI). We aimed to examine the correlation between STS and logistic EuroSCOREs and their performance characteristics in patients referred for TAVI. METHODS The study cohort consisted of 718 high-risk patients with severe aortic stenosis who were considered for participation in a TAVI clinical trial. The performance of the STS and logistic EuroSCOREs was evaluated in three groups: (a) medical management or balloon aortic valvuloplasty (BAV), 474 (66%); (b) 133 patients (18.5%) with surgical aortic valve replacement (AVR); (c) 111 (15.4%) with TAVI. The mean age was 81.8 ± 8.1 years, and 394 (54.8%) were female. RESULTS The mean STS score was 11.5 ± 6.1, and the mean logistic EuroSCORE was 39.7 ± 23.0. Pearson correlation coefficient showed moderate correlation between the STS and logistic EuroSCOREs (r = 0.61, P < .001). At a median follow-up of 190 days (range, 67-476), 282 patients (39.2%) died. The STS and logistic EuroSCOREs were both higher in patients who died as compared to those in survivors (13.1 ± 6.2 vs.10.0 ± 5.8 and 43.4 ± 23.1 vs. 37.5 ± 22, respectively; P < .001). The observed and predicted 30-day mortality rates in the medical/BAV group were 10.1% observed, 12.3% by STS and 43.1% by logistic EuroSCORE. In the surgical AVR group, the rates were 12.8% observed, 8.4% by STS and 25.6% by logistic EuroSCORE. In the TAVI group, the rates were 11.7% observed, 11.8% by STS and 41.2% by logistic EuroSCORE. The odds ratio (OR) for 30-day mortality in the medical/BAV group was 1.05 (P = .01) with STS and 1.003 (P = .7) with logistic EuroSCORE. In the surgical AVR group, the OR was 1.09 (P = .07) with STS and 1.007 (P = .6) with logistic EuroSCORE. In the TAVI group, the OR was 1.14 (P = .03) with STS and 1.03 (P = .04) with logistic EuroSCORE. CONCLUSION In high-risk patients with severe aortic stenosis, STS score is superior to the logistic EuroSCORE in predicting mortality. Clinical judgment should play a major role in the selection of patients with severe aortic stenosis for the different therapeutic options.

Correlation between Light Transmission Aggregometry, VerifyNow P2Y12, and VASP-P Platelet Reactivity Assays Following Percutaneous Coronary Intervention

BACKGROUND High on-treatment platelet reactivity is an established risk factor for adverse cardiac events in patients taking clopidogrel following percutaneous coronary intervention (PCI). METHODS Two hundred patients underwent platelet reactivity testing with VerifyNow P2Y12, vasodilator-stimulated phosphoprotein phosphorylation (VASP), and light transmission aggregometry (LTA) with both 5 and 20 μM of adenosine diphosphate (ADP) following PCI. High on-treatment platelet reactivity was defined as a maximum platelet aggregation ≥46% for LTA ADP 5 μM or ≥60% for 20 μM; platelet reactivity index (PRI) ≥50% for VASP; and platelet reactivity units ≥235 for VerifyNow. Correlation between assays was tested using Spearman coefficients (ρ); agreement among tests in regards to high on-treatment platelet reactivity was evaluated with Kappa statistics (κ). RESULTS All Spearman correlations had P values <0.001, although ρ ranged from 0.60-0.86. The incidence of high on-treatment platelet reactivity was 39.3% with VASP, 27.3% with VerifyNow, 23.1% with LTA ADP 5 μM, and 16.2% with LTA ADP 20 μM. The strongest correlation was between LTA ADP 5 μM and LTA ADP 20 μM (κ= 0.53, 95% CI 0.37-0.68); the weakest was between VASP and LTA ADP 5 μM (κ= 0.33, 95% CI 0.19-0.47). Overall, the level of agreement between assays was in the moderate to poor range. CONCLUSION Despite evidence that the most commonly used tests are correlated, agreement among tests is modest at best and demonstrates they are not interchangeable. 

Effect of Insurance Type on Adverse Cardiac Events After Percutaneous Coronary Intervention

Previous studies have documented disparities in both access to invasive cardiovascular procedures and outcomes in patients with Medicaid, Medicare, or no insurance. Outcomes by insurance have yet not been examined in a percutaneous coronary intervention (PCI) population. Data from patients undergoing PCI from June 2000 to June 2009 were retrospectively analyzed. Insurance was categorized as private, Medicare, Medicaid, and uninsured, according to the primary insurance at discharge. The outcome variable of interest was major adverse cardiac events (a composite of death, Q-wave myocardial infarction, and target vessel revascularization) at 1 year. Multivariable Cox regression analysis was stratified according to age <65 and ≥65 years. Of the 13,573 patients who had undergone PCI, 6,653 (49.0%) had private insurance, 6,150 (45.3%) had Medicare, 486 (3.6%) had Medicaid, and 284 (2.1%) were uninsured. Of the patients <65 years old, Medicaid (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.04 to 2.43), Medicare (HR 2.18, 95% CI 1.58 to 2.99), and no insurance (HR 2.41, 95% CI 1.36 to 4.27) were associated with greater rates of adjusted major adverse cardiac events at 1 year compared with private insurance. Of the patients ≥65 years old, only Medicaid (HR 3.07, 95% CI 1.09 to 8.61) was associated with a greater rate of adjusted major adverse cardiac events at 1 year. In conclusion, patients with government-sponsored insurance and no insurance have worse cardiovascular outcomes than patients with private insurance after PCI at 1 year. This implies that the provision of health insurance alone might not have a dramatic effect on cardiovascular outcomes after PCI.

Association Between Bleeding Severity and Long-Term Mortality in Patients Experiencing Vascular Complications After Percutaneous Coronary Intervention

Vascular complications (VCs) occur in 3% to 8% of percutaneous coronary interventions (PCIs). However, only a portion of patients who experience VCs bleed significantly. The aim of this study was to assess the covariates associated with the amount of blood loss in patients experiencing postprocedural VCs as well as the effect of the degree of blood loss on long-term mortality. Overall, 7,718 unselected patients who underwent PCI through femoral access were evaluated. Those experiencing VCs were identified and stratified with regard to the degree of hematocrit (HCT) decrease after the procedure. In total, 444 patients (5.8%) had VCs. Compared to those without VCs, patients with VCs were older and had more extensive co-morbidities. Severe blood loss was most frequent in those who had vascular perforation requiring surgical repair or in those who had retroperitoneal bleeding. Overall, <25% of patients with hematoma had severe blood loss. The raw 1-year mortality was doubled in patients with minimal or moderate HCT decrease and was tripled in those with severe decreases in HCT. Similarly, the rate of definite stent thrombosis was tripled in patients with VCs and moderate or severe decreases in HCT. After adjustment, only patients with VCs and the greater HCT decreases had an increased risk for death at 1 year (hazard ratio 1.80, 95% confidence interval 1.03 to 3.14). Independent predictors of severe HCT decrease included age, female gender, glycoprotein IIb/IIIa inhibitor use, and activated clotting time peak. Bivalirudin and closure devices were independently associated with less frequent severe HCT decrease. In conclusion, VCs do not entail an increased risk for death at 1 year unless associated with severe blood loss. The use of bivalirudin and closure devices seems to reduce the risk for such complications.

Impact of smoking on acute phase outcomes of myocardial infarction

ObjectivesPrevious studies have found an apparent paradox in smokers: acute phase outcomes after an acute myocardial infarction are superior to those of nonsmokers. Furthermore, it is reported that smoking has an impact on the metabolism of clopidogrel. This study aimed to examine whether this paradoxical finding exists in patients who undergo drug-eluting stent implantation and are treated with clopidogrel. MethodsFrom April 2003 to June 2010, 1424 consecutive patients with acute myocardial infarction who underwent primary or rescue percutaneous coronary intervention with drug-eluting stent and clopidogrel were enrolled. They were divided into three groups: current smokers (n=486); previous smokers (n=349); and nonsmokers (n=589). The primary end point was a composite of 30-day, all-cause death, nonfatal myocardial infarction, or definite stent thrombosis. ResultsCompared with nonsmokers, current smokers were younger (P<0.001) and more often men (P<0.001). They had larger myocardial infarctions than did nonsmokers [maximum troponin I, 8.9 (2.4, 38.4) vs. 6.8 (1.4, 30.1) ng/ml, P=0.01]. Current smokers less frequently met the primary end point than did nonsmokers (2.9 vs. 6.1%, P=0.01). However, after adjustment for baseline and angiographic characteristics, the beneficial effect of smoking was no longer seen (odds ratio 1.35, confidence interval: 0.53–3.44, P=0.5). ConclusionA beneficial effect of smoking (‘smokers paradox’) in the unadjusted primary end point continues to be present; however, after adjustment for differences in baseline characteristics, no benefit was detectable.

Relation of Body Mass Index to On-Treatment (Clopidogrel + Aspirin) Platelet Reactivity

Previous research has suggested that obesity is associated with increased high on-treatment platelet reactivity. We therefore tested platelet reactivity in 251 patients with VerifyNow P2Y12, vasodilator-stimulated phosphoprotein phosphorylation, and light transmission aggregometry with adenosine diphosphate 5 and 20 μM 6 to 24 hours after percutaneous coronary intervention. High on-treatment platelet reactivity was defined as a maximum platelet aggregation ≥46% for light transmission aggregometry with adenosine diphosphate 5 μM or ≥60% for 20 μM, platelet reactivity index ≥50% for vasodilator-stimulated phosphoprotein phosphorylation, and P2Y12 reaction units ≥235 for VerifyNow. The relation between body mass index (BMI) and platelet reactivity values was examined with Spearman coefficients; BMI and high on-treatment platelet reactivity were assessed with Students t test. Multivariable logistic regression for high on-treatment platelet reactivity was also performed. Average BMI was 30.3 ± 5.9 kg/m² and 44% of patients had a BMI ≥30 kg/m². Overall there was very poor correlation between BMI and on-treatment platelet reactivity, with Spearman coefficients ranging from 0.08 to 0.10. BMI was also not associated with the various definitions of high on-treatment platelet reactivity. Multivariable logistic regressions showed no association between BMI and high on-treatment platelet reactivity. In conclusion, and contrary to previous reports, we found no association whatsoever between BMI and on-treatment platelet reactivity as quantified by a variety of platelet function tests.

Comparison of Long-Term Outcomes Between Everolimus-Eluting and Sirolimus-Eluting Stents in Small Vessels

Although second-generation everolimus-eluting stents (EESs) have demonstrated superiority over first-generation paclitaxel-eluting stents for a broad subset of patients and lesions, it is unclear whether the same applies to sirolimus-eluting stents (SESs). The present study compared the long-term clinical outcomes between EESs and SESs in patients with small coronary artery disease. A cohort of 643 patients treated with EESs (220 patients with 245 lesions) or SESs (423 patients with 523 lesions) in small vessel lesions (defined as those receiving stents ≤2.5 mm) were retrospectively analyzed. The end points included target lesion revascularization, target vessel revascularization, major adverse cardiovascular events (all-cause death, myocardial infarction, or target lesion revascularization), and definite stent thrombosis at 1 year of follow-up. The baseline characteristics were generally similar between the 2 groups, except that more systemic hypertension was seen in the EES group and more patients had a family history of coronary artery disease in the SES group. The 1-year target lesion revascularization (5.6% vs 4.8%, p = 0.68) and target vessel revascularization (5.6% vs 7.6%, p = 0.33) rates showed no significant differences between the EES and SES groups. Overall major adverse cardiovascular events occurred in 9.1% of the EES- and 8.6% of SES-treated patients (p = 0.83). This similar major adverse cardiovascular events rate remained after adjustment. The rate of stent thrombosis was 0% in the EES group and 1.2% in the SES group (p = 0.17). In conclusion, EESs demonstrated comparable clinical outcomes to those of SESs in small vessel interventions. The absence of stent thrombosis among patients treated with EESs suggests a good safety profile for this second-generation drug-eluting stent, which should be carefully studied in a larger series of patients with small vessel disease.

Clinical Outcomes and Treatment After Drug-Eluting Stent Failure The Absence of Traditional Risk Factors for In-Stent Restenosis

Background— The optimal percutaneous treatment of drug-eluting stent (DES) in-stent restenosis (ISR) and the correlates for recurrent DES ISR remain unclear. Methods and Results— From 2003 to 2008, 563 patients presenting with recurrent symptoms of ischemia and angiographic ISR after DES implantation were included. Of these, 327 were treated with re-DES (58.1%), 132 underwent vascular brachytherapy (23.4%), and 104 were treated with conventional balloon angioplasty (18.5%). Variables associated with target lesion revascularization at 1 year were explored by individual proportional hazard models. This population presents a high prevalence of comorbidities, including diabetes (43.7%), previous myocardial infarction (MI) (45.8%), coronary bypass graft surgery (39.2%), chronic renal failure (18.8%), and heart failure (17.3%). Baseline clinical characteristics were balanced among the 3 groups; however, patients undergoing vascular brachytherapy presented with more complex lesions and a higher prevalence of prior stent/vascular brachytherapy failure than did the rest of the population. The overall incidence of recurrent DES failure at 1-year follow-up was 12.2%, which was similar among the 3 groups (P=0.41). The rate of the composite end point (death, Q-wave-MI and target lesion revascularization) at 1-year follow-up was 14.1% for re-DES, 17.5% for vascular brachytherapy, and 18.0% for conventional balloon angioplasty (P=0.57). After univariable analysis tested the traditional known covariates related to ISR, none of them were associated with repeat target lesion revascularization. Conclusions— Recurrence of ISR after DES treatment failure is neither infrequent nor benign, and optimal therapy remains unclear and challenging. Given the absence of traditional risk factors for ISR in this population, further research is required to elucidate both the correlates involved in DES ISR and the optimal treatment for this condition.

Outcome of Percutaneous Coronary Intervention Utilizing Drug-Eluting Stents in Patients With Reduced Left Ventricular Ejection Fraction

Ischemic cardiomyopathy with depressed left ventricular ejection fraction (LVEF) is predictive of death after percutaneous coronary intervention (PCI), but its association with stent thrombosis (ST) and the need for repeat revascularization is less clearly defined. In total 5,377 patients undergoing PCI were retrospectively evaluated. Multivariable Cox proportional hazards regression and competitive outcome analysis were employed. The primary end point was 1-year major adverse cardiac events (all-cause death, Q-wave myocardial infarction, ST, and target lesion revascularization [TLR]). Individual end points of ST and of TLR were also evaluated. Patients with normal LVEF (>50%) were compared to those with mild (41% to 50%), moderate (25% to 40%), and severe (<25%) decreases in LVEF. Patients with abnormal LVEF were older and more commonly diabetic and had renal insufficiency and heart failure syndrome (p <0.001 for all variables). These patients demonstrated more angiographically complex lesions and less frequently received a drug-eluting stent. The primary end point was significantly increased in patients with lower LVEF (9.7% for normal LVEF vs 20.6% for severely decreased LVEF, p <0.001). ST occurred more frequently in these patients (1.4% for normal LVEF vs 6% for severely decreased LVEF, p <0.001), but clinically driven TLR did not significantly change across LVEF categories. After adjustment, only moderate and severe LVEF decreases (i.e., LVEF ≤40%) demonstrated an association with major adverse cardiac events and with the individual outcome of ST. Subgroup analysis of patients receiving only a drug-eluting stent or a bare-metal stent demonstrated no statistically significant differences for the probability of ST. In conclusion, decreased LVEF is not associated with clinically driven TLR but does increase the risk of ST. Patients with LVEF ≤40% appear to be at significantly higher risk for ST and therefore might benefit from interventional and pharmacologic strategies aimed at minimizing this risk.