Does Extended Use of Clopidogrel-Based Dual Anti-Platelet Therapy Increase the Risk of Gastrointestinal Bleeding?

BACKGROUND: Clopidogrel-based dual anti-platelet therapy (CDAPT) has shown significant benefits in the management of coronary artery disease (CAD), up to 1-year duration. Gastrointestinal bleeding (GIB) is one of the limiting factors for prolonged use of CDAPT. METHODS: We identified all patients taking CDAPT from our ambulatory clinics. Demographic, clinical, laboratory and pharmacological data were abstracted. American Heart Association (AHA) guidelines were used to determine the duration of CDAPT therapy. The study population was divided into two groups based on the duration of therapy. Individuals who received CDAPT more than 12 months were deemed as extended use. RESULTS: A total of 351 patients with CAD were taking CDAPT. Majority of patients (276/351, 79%) were taking CDAPT beyond 1 year. There were no differences in baseline characteristics between the two groups. There was no significant difference in the incidence of GIB between the two groups. However, in subgroup analysis, there was a significant difference in the incidence of GIB in men. Men who were taking CDAPT beyond 12 months had almost three times higher incidence of GIB compared to those who were taking less than 12 months (25% vs. 8%, P = 0.04). The excess GIB in men prevailed despite adjusting for non-steroidal anti-inflammatory drugs (NSAIDs) or direct oral anticoagulant (DOAC) use. CONCLUSIONS: We found that a majority of patients were taking CDAPT beyond the recommended duration. We observed that men taking CDAPT for an extended duration had a three times higher incidence of GIB. It would be reasonable for physicians to be aware of the higher risk of GIB in men and carefully assess the risks and benefits of extended use of CDAPT.

Recurrent intrathoracic dedifferentiated liposarcoma: A case report and literature review.

BACKGROUND: Liposarcoma (LPS) is the second most common type of soft tissue sarcoma, accounting for approximately 15-20% of all the sarcomas. Primary intrathoracic LPS, however, is quite rare. LPS is a malignant mesenchymal tumor, comprised of lipogenic tissue with varying degrees of atypia. It can be subclassified into well-differentiated LPS (WDLPS), myxoid LPS (MLPS)/round cell LPS, pleomorphic LPS (PLPs), and dedifferentiated LPS (DDLPS), based on the histology. CASE PRESENTATION: A 76-year-old male patient initially presented to the emergency room with a complaint of precordial chest pain for one month. Computed tomography (CT) of his chest showed a large, 8 cm × 8 cm x 10 cm, supradiaphragmatic, complex solid mass in the lower left hemithorax, along the anterior chest wall. Chest wall mass excision revealed dedifferentiated LPS, with excision of margins. Positron emission tomography (PET) scan did not show metastatic disease. Seven months later, he presented with shortness of breath, and CT of the chest showed large, left pleural-based masses, causing compression of surrounding structures. He was not a candidate for surgical resection. This patient subsequently failed chemotherapy and opted for hospice. CONCLUSION: Intrathoracic LPS is a rare tumor. Recurrence is higher with dedifferentiated histology forms. Radical surgery with excision of margins is the primary recommended treatment.

Prevalence, correlates, and impact of coronary calcification on adverse events following PCI with newer-generation DES: Findings from a large multiethnic registry.

OBJECTIVES: We sought to determine the prevalence, predictors, and clinical impact of target lesion calcification in patients undergoing percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES) and devices. BACKGROUND: Coronary calcification is independently associated with adverse outcomes following PCI. While newer DES and contemporary devices are considered safer and more efficacious, their influence on outcomes following PCI of heavily calcified lesions is unknown. METHODS: We performed a retrospective analysis of a large, multiethnic cohort of patients undergoing PCI with new generation DES at an academic center between 2009 and 2013. Coronary calcification was qualitatively assessed as none/mild, moderate, or severe. Independent demographic, clinical, and anatomic predictors of moderate/severe calcification were identified using logistic regression. Associations between coronary calcification and 1-year MACE (death, myocardial infarction, or target vessel revascularization) were examined using Cox modeling. RESULTS: Compared to patients with none/mild (n = 10,180; 82.0%), those with moderate (n = 1,271; 10.0%) or severe (n = 994; 8.0%) calcification were older, more often Caucasian, had more complex target lesions, and worse renal function. The strongest demographic, clinical, and anatomic correlates of moderate/severe calcification were age, Caucasian race, renal dysfunction, lesion length, and left main location. Unadjusted MACE rates among those with none/mild, moderate, and severe calcification were 8.3, 14.6, and 17.8%, respectively (P < 0.001). After multivariable adjustment, the hazard ratio (95% CI) for MACE associated with moderate or severe coronary calcification was 1.63. CONCLUSIONS: Target lesion calcification remains independently associated with adverse outcomes in patients treated with newer generation DES and modern devices.

A comparative study of odontogenic keratocyst and orthokeratinized odontogenic cyst using Ki67 and α smooth muscle actin.

AIM: This study aimed to demonstrate and evaluate the expression of stromal myofibroblasts (MFs) and epithelial cell proliferation using α-smooth muscle actin (α-SMA) and Ki67 markers, respectively, in odontogenic keratocyst (OKC) and orthokeratinized odontogenic cyst (OOC) to correlate their aggressive behavior. MATERIALS AND METHODS: Twenty cases of OKC and twenty cases of OOC were stained with α-SMA and Ki67 markers for demonstration of stromal MFs and epithelial cell proliferation, respectively, and ten cases of well-differentiated squamous cell carcinoma were used as positive control. Assessment of the number of α-SMA-positive stromal cells and Ki67-positive epithelial cells determined by MFs and proliferative epithelial cell frequency in 10 high-power fields (×400) was presented as the mean number of positive cells per field. STATISTICAL ANALYSIS: Kruskal-Wallis and Mann-Whitney test were used to analyze the difference in the mean number of α-SMA- and Ki67-positive cells per field between OKC and OOC. RESULTS: The mean number of positively stained cells for α-SMA and Ki67 is significantly higher in OKC compared to OOC. CONCLUSION: Impression is that, the different behaviors of these two entities are compatible with their immunohistochemical view. The high value of stromal MFs and proliferative epithelial cells in OKC in comparison to OOC indicates its aggressiveness and potential for recurrence.

Intracoronary brachytherapy for in-stent restenosis of drug-eluting stents.

PURPOSE: Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population. METHODS AND MATERIALS: A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired t tests and χ2 tests were used to compare the groups. RESULTS: There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, P = .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group (P = .649). CONCLUSIONS: This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.

Dedicated two-stent technique in complex bifurcation percutaneous coronary intervention with use of everolimus-eluting stents: the EES-bifurcation study.

OBJECTIVES: To compare the outcomes of initial one-stent (1S) versus dedicated two-stent (2S) strategies in complex bifurcation percutaneous coronary intervention (PCI) using everolimus-eluting stents (EES). BACKGROUND: PCI of true bifurcation lesions is technically challenging and historically associated with reduced procedural success and increased restenosis. Prior studies comparing initial one-stent (1S) versus dedicated two-stent (2S) strategies using first-generation drug-eluting stents have shown no reduction in ischemic events and more complications with a 2S strategy. METHODS: We performed a retrospective study of 319 consecutive patients undergoing PCI at a single referral center with EES for true bifurcation lesions, defined by involvement of both the main vessel (MV) and side branch (SB). Baseline, procedural characteristics, quantitative coronary angiography and clinical outcomes in-hospital and at one year were compared for patients undergoing 1S (n=175) and 2S (n=144) strategies. RESULTS: Baseline characteristics were well-matched. 2S strategy was associated with greater SB acute gain (0.65±0.41 mm vs. 1.11±0.47 mm, p<0.0001). In-hospital serious adverse events were similar (9% with 2S vs. 8% with 1S, p=0.58). At one year, patients treated by 2S strategy had non-significantly lower rates of target vessel revascularization (5.8% vs. 7.4%, p=0.31), myocardial infarction (7.8% vs. 12.2%, p=0.31) and major adverse cardiovascular events (16.6% vs. 21.8%, p=0.21). CONCLUSION: In this study of patients undergoing PCI for true coronary bifurcation lesions using EES, 2S strategy was associated with superior SB angiographic outcomes without excess complications or ischemic events at one year.

GuideLiner mother-and-child guide catheter extension: a simple adjunctive tool in PCI for balloon uncrossable chronic total occlusions.

OBJECTIVES: To investigate the use of the GuideLiner "mother-and-child" guide catheter extension system as a simple solution to facilitate initial device delivery in balloon uncrossable chronic total occlusions (CTOs) undergoing percutaneous coronary intervention (PCI). BACKGROUND: During PCIs for CTO lesions, an important reason for procedural failure is the inability to deliver a balloon or microcatheter across the lesion. METHODS: We retrospectively accessed our interventional registry for 07/01/2010 to 03/21/2012 and extracted data on all CTO lesions involving GuideLiner catheter use. Cine review was performed to identify cases where a guidewire had crossed the CTO and the use of a GuideLiner catheter facilitated initial device delivery. RESULTS: We identified 28 patients that underwent PCI for CTO with a GuideLiner catheter used to assist initial balloon or microcatheter advancement across the culprit lesion. Mean overall CTO length was 26.3 ± 18.1 mm. The GuideLiner catheter was successful in delivering a small balloon to the CTO lesion in 85.7% of cases (24/28). A single CTO PCI resulted in a distal guidewire perforation, but there was no hemodynamic compromise or pericardial effusion and the patient was discharged the next day. Overall procedural success in these selected cases (where a guidewire had already crossed the CTO) was 89.3% (25/28). CONCLUSIONS: The GuideLiner mother-and-child catheter is a simple, safe and efficacious adjunctive device for difficult CTO PCIs where despite standard measures it is not possible to deliver an initial balloon or microcatheter across the occluded segment.

Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity.

Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4-6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 - 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.

Comparison of six risk scores in patients with triple vessel coronary artery disease undergoing PCI: competing factors influence mortality, myocardial infarction, and target lesion revascularization.

OBJECTIVES: To compare the discriminatory value of differing risk scores for predicting clinical outcomes following PCI in routine practice. BACKGROUND: Various risk scores predict outcomes after PCI. However, these scores consider markedly different factors, from purely anatomical (SYNTAX risk score [SRS]) to purely clinical (ACEF, modified ACEF [ACEFmod], NCDR), while other scores combine both elements (Clinical SYNTAX score [CSS], NY State Risk Score [NYSRS]). METHODS: Patients with triple vessel and/or LM disease with 12 month follow-up were studied from a single center PCI registry. Exclusion criteria included STEMI presentation, prior revascularization and shock. Clinical events at 12 months were compared to baseline risk scores, according to score tertiles and area under receiver-operating-characteristic curves (AUC). RESULTS: We identified 584 eligible patients (69.8±12.3yrs, 405 males). All scores were predictive of mortality, with the SRS being least predictive (AUC=0.66). The most accurate scores for mortality were the CSS and ACEF (AUC=0.76 for both: P = 0.019 and 0.08 vs. SRS, respectively). For TLR, while the SRS trended toward being positively predictive (P = 0.075), several scores trended towards a negative association, which reached significance for the NCDR (P = 0.045). The SRS and CSS were the only scores predictive of MI (both P < 0.05). No score was particularly accurate for predicting MACE (death+MI+TLR), with AUCs ranging from 0.53 (NCDR) to 0.63 (SRS). CONCLUSIONS: Competing factors influence mortality, MI and TLR after PCI. An increasing burden of comorbidities is associated with mortality, whereas anatomical complexity predicts MI. By combining these outcomes to predict MACE, all scores show reduced utility.