Platelet HPA-1 a/HPA-1 b polymorphism and the risk of periprocedural myocardial infarction in patients undergoing elective PCI

Abstract

Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI) and large interests have been focused on platelets in order to prevent such a complication. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related to an increased platelet reactivity, a lower response to antiplatelet agents and higher risk of stent restenosis. Therefore, aim of our study was to evaluate the impact of this polymorphism on PMI in elective patients undergoing PCI. Our population is represented by 422 consecutive patients with cardiac biomarkers within normality undergoing elective PCI. We measured cardiac biomarkers (CK–MB and Troponin I) at baseline, and 8, 24 and 48 hours after the procedure. For all subjects, we performed genetic analysis to assess the presence of Leu33Pro polymorphism. A total of 136 patients (32.2%) were polymorphic. Those patients were younger (p?=?0.03) and more often dislypidemic (p?=?0.01). Angiographic features did not differ according to genetic status. Pharmacological treatment pre and during angioplasty was similar. PCI-related complications did not differ according to genotype, with the only exception of higher rate of distal embolization in polymorphic patients. However, Leu33Pro polymorphism was not associated with increased risk of periprocedural myonecrosis and PMI even after correction for baseline differences, (respectively OR?=?1.22 [0.81–1.84], p?=?0.34 for myonecrosis and OR?=?1.66 [0.85–3.23]; p?=?0.14 for PMI). At subgroup analysis, the Leu33Pro substitution was associated with higher risk of PMI only among diabetics (adjusted OR?=?4.46 [1.12–17.76], p?=?0.03). Among patients undergoing elective PCI, the polymorphism Leu33Pro of platelet glycoprotein IIIa is associated with increased risk of PMI only in diabetic patients.     

Predictors of antiplatelet response to prasugrel during maintenance treatment

Insufficient P2Y12 receptor inhibition is associated with a higher risk of thrombotic events after percutaneous coronary intervention (PCI). The third generation thienopyridine prasugrel achieves stronger platelet inhibition as compared to its predecessor clopidogrel. Little is known about predictors of prasugrel drug responsiveness. The aim of this study was to explore predictors of prasugrel responsiveness in patients with a recent PCI on prasugrel maintenance dose (MD) treatment. In a registry of PCI-treated patients (n?=?163, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA) was assessed on a Multiplate analyzer. The mean (interquartile range (IQR)) ADP-induced PA on prasugrel MD treatment was 206 (138–331) AU?×?min. Obese (defined by a body mass index (BMI)?≥?30) patients (n?=?42) (303 [192–467] vs. 187 [117–305] AU?×?min, p?=?0.0001), patients (n?=?70) with a history of clopidogrel low responsiveness (278 [161–409] vs. 192 [126–282] AU?×?min, p?=?0.002) and patients (n?=?18) on a low (5?mg) prasugrel MD (483 [252–798] vs. 198 [133–313] AU?×?min; p?=?0.0001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model, the latter three variables were independently associated with higher PA values on prasugrel MD treatment. In summary response variability is observed in patients on prasugrel MD treatment. Obesity, a history of clopidogrel low responsiveness and a reduced prasugrel MD of 5?mg are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.     

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study

Background

Potent P2Y₁₂ inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type.

Effect of platelet receptor gene polymorphisms on outcomes in ST-elevation myocardial infarction patients after percutaneous coronary intervention

Polymorphisms in platelet receptor genes may influence platelet function. This study aimed to assess the impact of five polymorphisms of genes encoding platelet receptors on the risk of ischemic and bleeding events in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). 503 consecutive Chinese patients with STEMI after an uneventful PCI and exposed to standard dual antiplatelet therapy for 12 months were enrolled. Polymorphisms of platelet receptors, GPIa (ITGA2, 807C?>?T, rs1126643), GPVI (GP6, 13254T?>?C, rs1613662), PAR-1 (F2R, IVS-14A?>?T, rs168753) and P2Y12 (P2RY12, 34C?>?T, rs6785930 and H1/H2 haplotype, 52G?>?T, rs6809699) were detected by the ligase detection reaction. The follow-up period was 12 months. Overall, 34 (6.8%) ischemic events occurred and 46 (9.1%) major bleedings occurred. Multivariate Cox regression analysis showed the carriage of F2R rs168753 minor allele was an independent predictor of the composite ischemic events (HR 0.387, 95% CI 0.193–0.778, p?=?0.008) after adjusted for established risk factors. Multivariate logistic regression model identified that carriage of P2RY12 rs6809699 minor allele (OR 2.71, 95% CI 1.298–5.659, p?=?0.008) was an independent predictor of major bleedings. The associations were then validated in a second cohort of 483 STEMI patients. In STEMI patients after PCI, F2R rs168753 minor allele could significantly contribute to the risk of ischemic events, and P2RY12 rs6809699 minor allele could predict bleedings. The genetic testing of platelet receptors can be valuable in predicting adverse events in STEMI patients after PCI.     

Monocyte–Platelets Aggregates as Cellular Biomarker of Endothelium-Dependent Coronary Vasomotor Dysfunction in Patients with Coronary Artery Disease

Monocyte–platelet aggregates (MPA) are increased in patients with acute coronary syndrome. We investigated whether MPA are associated with the presence of functionally significant coronary stenoses or with coronary arterial endothelial dysfunction. One hundred forty five patients undergoing elective coronary angiography were prospectively enrolled. Functional significance of coronary stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected patients underwent pacing protocol to evaluate Coronary endothelium-dependent vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with FFR?≤?0.8 (FFR_pos, n?=?75), MPA did not significantly differ from FFR >0.8 patients (FFR_neg, n?=?70) (38.1 % [25.7–56.6] vs 34.0 % [20.5–49.9], p?=?0.08). CVF was similar in FFR_pos and FFR_neg patients (percent vessel diameter change, %VDC?=?7.19 % [6.01–10.9] vs 8.0 % [0.81–9.80], p?=?0.78). Yet, patients with abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3 % [28.8–53.4] vs 20.5 % [17.0–32.9], p?=?0.01). Moreover, MPA was inversely correlated with %VDC (R ²?=?0.26, p?<?0.01). MPA levels are significantly higher in patients with abnormal coronary vasomotor function regardless of the presence of functionally significant coronary stenosis.     

Platelet adenosine diphosphate receptor antagonists: ticlopidine to ticagrelor-a long continuing journey

Platelet aggregation plays a central role in the pathogenesis of atherothrombosis. Platelet adenosine diphosphate (ADP) receptor antagonists (ticlopidine, clopidogrel, prasugrel, and ticagrelor) are a major advance in the treatment of atherothrombotic diseases, especially acute coronary syndromes (ACS). Ticlopidine was the first thienopyridine introduced into clinical practice, but its potentially serious haematological side-effects limited its use and it was quickly eclipsed by clopidogrel. Clinical trials established aspirin plus clopidogrel as the standard dual anti-platelet therapy in patients with ACS and patients undergoing percutaneous coronary intervention (PCI) with stenting. Clopidogrel was found to have pharmacokinetic and pharmacodynamic limitations. Prasugrel is the next approved thienopyridine that has shown superior efficacy in ACS patients undergoing PCI in comparison to clopidogrel, although at the cost of a higher bleeding risk. Ticagrelor is the latest non-thienopyridine ADP receptor blocker that is potent, effective, reversible, and relatively safer as compared to clopidogrel. Both prasugrel and ticagrelor are more potent than clopidogrel. The data so far suggests that ticagrelor has a wider applicability in usage in patients with ACS as compared to prasugrel. Prasugrel however seems to be better tolerated. Search is on for newer more potent but safer anti-platelet agents.     

Urates in exhaled breath condensate as a biomarker of control in childhood asthma

Objective: The aim of this study was to (1) investigate the possibility to use urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation and control in childhood asthma and (2) explore their association with other biomarkers of airway inflammation and clinical indices of asthma control (Asthma Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use, time from last exacerbation [TLE]. Methods: This cross-sectional study comprised 103 consecutive patients (age 6–18 years) divided in groups of uncontrolled ([NC], n?=?53) and controlled asthma ([C], n?=?50). Measured lung function and biomarkers included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), exhaled NO (F_ENO), pH and urates in EBC and exhaled breath temperature (EBT). Results: Statistically significant differences were found between groups for EBC urates, EBC pH and EBT (NC versus C: EBC urates, median [IQR], µmol/L; 10 [6] versus 45 [29], p?<?0.001; EBC pH, mean [SD], 7.2 [0.17] versus 7.33 [0.16], p?=?0.002; EBT mean [SD], °C; 34.26 [0.83], versus 33.90 [0.60], p?=?0.014). EBC urates showed significant association with TLE and F_ENO (r?=?0.518, p?<?0.001; r?=?0.369, p?=?0.007, respectively) in NC, and EBC pH (r?=?0.351, p?<?0.001), FEV₁ (r?=?0.222, p?=?0.024), ACT (r?=?0.654, p?<?0.001), PAQLQ (r?=?0.686, p?<?0.001) and prn salbutamol use (r?=??0.527, p?<?0.001) in all asthmatics. Conclusion: In our study, EBC urates were found to be the best single predictor of asthma control and underlying airway inflammation. Our results provide evidence supporting the potential utility to use EBC urates as an additional non-invasive biomarker of control in childhood asthma.     

Platelet glycoprotein IIIa Leu33Pro gene polymorphism and coronary artery disease: A meta-analysis of cohort studies

Great interest has been focused in the last year on genetic predictors of cardiovascular risk. Glycoprotein IIb/IIIa (GP IIb/IIIa), fibrinogen receptor, is the final common pathway for aggregation and a key point for atherothrombosis. A single nucleotide polymorphism of IIIa subunit (Leu33Pro-PlA¹/PlA² allele) has been suggested to increase aggregation and adhesion, however, contrasting reports have been reported so far on its effects on coronary artery disease (CAD). Aim of the current study was to perform a large meta-analysis including cohorts of patients undergoing coronary angiography in order to evaluate whether this polymorphism is associated with coronary artery disease. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for data of consecutive cohorts of patients undergoing coronary angiography, where PlA genotype was assessed. Primary endpoint was the prevalence of CAD. Secondary endpoint was severity of CAD defined as prevalence of multivessel disease (≥2 vessels). Data from seven studies were extracted, including a final number of 6700 patients. Among them 1893 (28.3%) carried the PlA² polymorphism, 163 of them in homozygosis. Angiographically defined CAD was present in 3573 (74.3%) PlA¹/PlA¹ patients and in 1430 (75.5%) PlA² carriers. PlA² polymorphism was not associated with an increased prevalence of coronary artery disease, (OR [95% CI]?=?1.07 [0.95–1.21], p?=?0.28, p_{heterogeneity}?=?0.39). Similar results were obtained for multivessel disease (OR [95% CI]?=?1.07[0.95–1.20], p?=?0.27, p_{heterogeneity}?=?0.12). Meta-regression analysis demonstrated a significant inverse relationship between the risk of CAD among the PlA² carriers and ageing (r?=??0.044, (?0.09, ?0.0008), p?=?0.046). Present meta-analysis demonstrates that 33Leu?→?Pro substitution of GPIIIa does not influence the prevalence and extent of angiographically defined coronary artery disease in general population, although apparently playing a role among younger patients.     

Chronic traffic pollution exposure is associated with eosinophilic,but not neutrophilic inflammation in older adult asthmatics

Abstract

Objective: Airway inflammatory patterns in older asthmatics are poorly understood despite high asthma-related morbidity and mortality. In this study, we sought to define the relationship between exposure to traffic pollutants, biomarkers in induced sputum, and asthma control in older adults. Methods: Induced sputum was collected from 35 non-smoking adults ≥65 years with a physician’s diagnosis of asthma and reversibility with a bronchodilator or a positive methacholine challenge. Patients completed the Asthma Control Questionnaire (ACQ), and Elemental Carbon Attributable to Traffic (ECAT), a surrogate for chronic diesel particulate exposure, was determined. Equal numbers of subjects with high (≥0.39?µg/m³) versus low (<0.39?µg/m³) ECAT were included. Differential cell counts were performed on induced sputum, and myeloperoxidase (MPO) and eosinophil peroxidase (EPO) were measured in supernatants. Regression analyses were used to evaluate the relationship between sputum findings, ACQ scores, and ECAT. Results: After adjustment for potential confounders, subjects with poorly controlled asthma based on ACQ?≥?1.5 (n?=?7) had significantly higher sputum eosinophils (median?=?4.4%) than those with ACQ?<?1.5 (n?=?28; eosinophils?=?2.6%; β?=?10.1 [95% CI?=?0.1–21.0]; p?=?0.05). Subjects with ACQ?≥?1.5 also had significantly higher sputum neutrophils (84.2% versus 65.2%; β?=?7.1 [0.2–14.6]; p?=?0.05). Poorly controlled asthma was associated with higher sputum EPO (β?=?2.4 [0.2–4.5], p?=?0.04), but not MPO (p?=?0.9). High ECAT was associated with higher eosinophils (β?=?10.1 [1.8–18.4], p?=?0.02) but not higher neutrophils (p?=?0.6). Conclusions: Poorly controlled asthma in older adults is associated with eosinophilic and neutrophilic inflammation. Chronic residential traffic pollution exposure may be associated with eosinophilic, but not neutrophilic inflammation in older asthmatics.     

Wheezes and desert breezes: when asthma and valley fever collide

Objective: To evaluate interactive effects of pulmonary coccidioidomycosis and asthma.

Methods: We identified three groups of 33 age- and sex-matched patients: Group 1 (both asthma and coccidioidomycosis), Group 2 (asthma only), and Group 3 (pulmonary coccidioidomycosis only). Predetermined end points included: rate of disseminated coccidioidomycosis, duration of symptoms and antifungal therapy, hospitalization, death, and escalation of asthma therapies.

Results: Baseline characteristics were similar across groups. Group 1 patients had worsening asthma outcomes (except forced expiratory volume in 1?s) with coccidioidomycosis. They required more asthma medications (median, 2.0 vs 0.0; p?<?0.001), more corticosteroids (mean [SD], 0.9 [4.2] vs 0.3 [0.6]; p?<?0.001), and more healthcare visits (mean [SD], 0.2 [0.4] vs 0.1 [0.3]; p?=?0.03). Groups 1 and 3 had no differences in coccidioidal end points, including rates of dissemination (1 vs 0; p?>?0.99), symptom duration (mean, 15.2 vs 23.6 weeks; p?=?0.24), antifungal treatment (n?=?21 [63.6%] vs n?=?24 [72.7%]; p?=?0.60), and treatment duration (median, 26.5 vs 11 weeks; p?=?0.09). Ten patients in Group 1 versus none in Group 3 required systemic corticosteroids for coccidioidomycosis (p?<?0.001).

Conclusions: Active pulmonary coccidioidomycosis significantly worsens asthma outcomes. Asthma (or its treatment) does not worsen coccidioidal outcomes, despite increasing the likelihood of treatment with systemic corticosteroids.     

Safety and benefits of protamine administration to revert anticoagulation soon after coronary angioplasty. A meta-analysis

Recent studies suggests that bleeding complications are associated with worse clinical outcome and survival among patients undergoing coronary angioplasty. Thus, in the last years increasing interests have been focused on strategies to prevent bleeding complications. The administration of protamine after coronary stenting for early sheat removal seems very attractive to minimize local and systemic bleeding complications. Thus, the aim of the current study is to perform a meta-analysis of randomized and non-randomized trials evaluating the benefits and safety of protamine administration after coronary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to December 2009. The following key words were used: coronary angioplasty, primary angioplasty, coronary stenting, protamine, heparin neutralization, bleeding complications. Primary endpoints were death and major bleeding complications, respectively. Secondary endpoint was myocardial infarction. A total of 5 trials, 2 randomized and 3 non randomized were included in the meta-analysis, involving 6,762 patients (4,913 or 72.6% in the protamine group and 1,949 or 27.4% in the standard group). Protamine administration was not associated with difference in short-term mortality (2.8% vs. 2.7%, OR [95% CI] = 0.97 [0.69–1.37], P = 0.88, p_het = 1.0), but with a significant reduction in major bleeding complications (2.4% vs. 4.1%, OR [95% CI] = 0.51 [0.37–0.69], P < 0.0001, p_het = 0.53, NNT = 58.8). No difference was observed myocardial infarction (0.9% vs. 0.8%, OR [95% CI] = 1.14 [0.63–2.07], P = 0.66, p_het = 0.89). This meta-analysis shows that protamine administration after percutaneous coronary intervention seems to be safe and associated with a significant reduction in major bleeding complications. Pending the results of larger randomized trials, its use may be considered after coronary angioplasty.     

Off-pump surgery for the poor ventricle?

Severely decreased ejection-fraction is an established risk-factor for worse outcome after cardiac surgery. We compare outcomes of off-pump coronary artery bypass grafting (OPCAB) and on-pump CABG (ONCABG) in patients with severely compromised EF. From 2004 to 2009, 478 patients with a decreased EF ??35% underwent myocardial-revascularization. Patients received either OPCAB (n?=?256) or ONCABG (n?=?222). Propensity score (PS), including 50 preoperative risk-factors, was used to balance characteristics between groups. PS adjusted logistic regression analysis was performed to assess mortality and major adverse cardiac and cerebrovascular events (MACCE). A composite endpoint for major non-cardiac complications such as respiratory failure, renal failure, rethoracotomy was applied. Complete revascularization (CR) was assumed when the number of distal anastomoses was larger than that of diseased vessels. There was no difference for mortality (2.3 vs. 4.1%; PS-adjusted odds ratio (PS-OR)?=?1.05; p?=?0.93) and MACCE (13.7 vs. 17.6%; PS-OR?=?1.22; p?=?0.50) including myocardial-infarction (1.4 vs. 4.9%; PS-OR?=?0.39; p?=?0.26), low cardiac output (2.3 vs. 4.7%; PS-OR?=?0.75; p?=?0.72) and stroke (2.3 vs. 2.7%; PS-OR?=?0.69; p?=?0.66). OPCAB patients presented with a trend to less frequent occurrence of the non-cardiac composite (12.1 vs. 22.1%; PS-OR?=?0.54; p?=?0.059) including renal dysfunction (PAOR?=?0.77; 95% CI 0.31?C1.9; p?=?0.57), bleeding (PAOR?=?0.42; 95% CI 0.14?C1.20; p?=?0.10) and respiratory failure (PAOR?=?0.39; 95% CI 0.05?C3.29; p?=?0.39). The rate of complete revascularization was similar (92.2 vs. 92.8%; PS-OR?=?0.75; p?=?0.50). OPCAB in patients with severely decreased EF is safe and feasible. It may even benefit these patients in regard to non-cardiac complications and does not come at cost of less complete revascularization.     

Switching directly to prasugrel from clopidogrel results in greater inhibition of platelet aggregation in aspirin-treated subjects

Prasugrel, a novel P2Y₁₂ antagonist, achieves faster onset and greater inhibition of platelet aggregation than clopidogrel 300 and 600 mg loading doses (LD). We studied the safety, time course, and level of platelet inhibition when switching directly from clopidogrel 75 mg maintenance dose (MD) to a prasugrel 60 mg LD/10 mg MD or 10 mg MD regimen. Healthy subjects (n?=?39) on aspirin (81 mg/d) received a clopidogrel 600 mg LD followed by 10 days of clopidogrel MD (75 mg/d). Subjects were then randomized without a washout period to prasugrel 60 mg LD (n?=?16) followed by 10 days of prasugrel MD (10 mg/d) or to prasugrel MD (10 mg/d, n?=?19) for 11 days. Maximal platelet aggregation (MPA) to 20 µM ADP was measured by turbidimetric aggregometry. In subjects on clopidogrel 75 mg MD, mean MPA decreased from 39 to 12% by 30 minutes, and to 5% by 1 hour after a prasugrel 60 mg LD (p?<?0.001 for both) and from 37 to 28% (p?<?0.001) by 1 hour after a prasugrel 10 mg MD. During prasugrel MD, a new pharmacodynamic steady state MPA of ～24% (p?<?0.01 vs. clopidogrel MD) occurred within four to five days of switching from clopidogrel. Changing from clopidogrel to prasugrel did not increase bleeding episodes or other adverse events. Switching directly from clopidogrel MD to either prasugrel LD or MD was well tolerated and resulted in significantly greater levels of platelet inhibition than a clopidogrel 75 mg MD.     

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels

Background: The cause of anti-TNF-induced psoriasis is still unknown.

Objective: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels.

Methods: In this case-control study we identified 23 patients (21 with Crohn’s disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n?=?20), adalimumab (ADA, n?=?2), and certolizumab pegol (CZP, n=?1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis.

Results: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p?=?0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p?=?0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6?μg/mL [IQR 0.9–5.5] vs. 3.4?μg/mL [IQR 1.4–8.1], p?=?0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies.

Conclusion: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.     

Sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients

Clopidogrel is a prodrug that needs to be converted in vivo by several cytochrome (CYP) P450 iso-enzymes to become active. Both clopidogrel and the oral hypoglycemic drug class sulfonylureas are metabolized by the iso-enzyme CYP2C9. The objective of the study was to evaluate the relationship of sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients undergoing elective coronary stent implantation. In this prospective, observational study, on-clopidogrel platelet reactivity was quantified using adenosine diphosphate (ADP)-induced light transmittance aggregometry in 139 type 2 diabetes mellitus patients undergoing elective coronary stent implantation treated with clopidogrel and aspirin. High on-clopidogrel platelet reactivity was defined as >70.7% platelet reactivity to 20?µmol/L ADP. A total of 53 patients (38.1%) were on concomitant treatment with sulfonylureas. The remaining 86 patients were on other hypoglycemic drugs. On-clopidogrel platelet reactivity was significantly higher in patients with concomitant sulfonylurea treatment as compared to patients without concomitant sulfonylurea treatment (for 5?µmol/L ADP: 46.0%?±?11.8 vs. 40.6%?±?16.0; p?=?0.035, adjusted p?=?0.032 and for 20?µmol/L ADP: 64.6%?±?10.8 vs. 58.7%?±?15.5; p?=?0.019, adjusted p?=?0.017). The concomitant use of sulfonylureas was associated with a 2.2-fold increased risk of high on-clopidogrel platelet reactivity (OR 2.2, 95% CI 1.1–4.7, p?=?0.039 and after adjustment for confounders: OR_adj 2.0, 95% CI 1.0–5.7, p?=?0.048). Concomitant treatment with sulfonylureas might be associated with decreased platelet inhibition by clopidogrel in type 2 diabetes mellitus patients on dual antiplatelet therapy undergoing elective coronary stent implantation.     

Comparison of Clinical Efficacy and Safety of Clopidogrel Resinate With Clopidogrel Bisulfate in Patients Undergoing Percutaneous Coronary Intervention

Objective

A new polymeric salt form of clopidogrel, clopidogrel resinate (CR), is a resinate complex of the (+)-clopidogrel optical isomer wherein the (+)-clopidogrel isomer binds to a water-soluble cation exchange resin via sulfonic acid groups. CR was approved for marketing by the Korean Food and Drug Administration based on a Phase I bioequivalence study. However, no data are available regarding its impact on adverse clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).

Methods

Clopidogrel bisulfate (CB) was used exclusively from January 2004 through April 2010, after which CR was exclusively administered from May 2010 through September 2011, in 8 centers. We categorized the overall population (N?=?10,487) into two groups according to the prescribed clopidogrel type: CB (n?=?9,127) or CR (n?=?1,360). To minimize the covariate imbalance and confounding in comparing CB and CR, we used a multivariable Cox proportional hazard regression model and the propensity score (PS) method to identify a 1:1 matched cohort (n?=?2,470). We compared cumulative adverse outcomes during a 1-year follow-up after PCI in the overall population and in the PS-matched cohort.

Results

In the overall population, there is no difference in the 1-year cumulative event rates between the two groups (CB : CR) : composite of any death, nonfatal myocardial infarction or stroke (6.0 % vs. 6.0 %, adjusted HR, 0.82; 95 % CI, 0.61–1.11, p?=?0.57), stent thrombosis (0.4 % vs. 0.2 %; adjusted HR, 0.40; 95 % CI, 0.09–1.72, p?=?0.31), and bleeding (0.9 % vs. 0.6 %; adjusted HR, 0.67; 95 % CI, 0.28–1.58, p?=?0.22). In the PS-matched cohort, the overall findings were consistent.

Conclusions

In this large real-world PCI population, CR was as effective and as safe as CB in preventing adverse clinical outcomes.     

Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC

Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n?=?396). For all patients, median age at ASCT was 56 years (range, 26–71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR?=?2 [1.2–3.4], p?=?.01, and HR?=?2.3 [1.2–4.5], p?=?.01), disease status at time of ASCT (HR?=?1.7 [1.1–2.6], p?=?.01 and HR?=?1.8 [1.1–3.1], p?=?.03), and use of rituximab (HR?=?0.5 [0.3–0.8], p?=?.002 and HR?=?0.5 [0.3–0.9], p?=?.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.     

Number of parity and the risk of non-Hodgkin lymphomas: a dose–response meta-analysis of observational studies

Background: Epidemiological reports have shown that parity is associated with a risk of developing non-Hodgkin lymphomas (NHL). However, the findings have been inconsistent.

Methods: We searched the EMBASE and PubMed databases for eligible studies up to 10 March 2016. Category and generalized least square regression models were used to perform data analyses.

Results: In total, five cohort and seven case–control studies were identified. Categorical analyses indicated that parity number has little association with NHL and its subtypes. In dose–risk analyses, there were no relationships between parity and NHL risk (p_{for association}?=?0.064; n?=?10). The summarized risk ratio (RR) was 0.97 (95% confidence interval (CI): 0.95–1.00; I²?=?57.8%; p_{heterogeneity}?=?0.014; Power?=?0.79) for each additional live birth increase. Similarly, for B-cell NHL, there was a null association between parity and NHL risk (p_{for association}?=?0.121; n?=?5). The combined RR was 0.96 (95% CI?=?0.90–1.03; I²?=?63.7%; p_{heterogeneity}?=?0.026; Power?=?0.71) for each additional live birth. For follicular NHL, there was still a non-significant association identified (p_{for association}?=?0.071; n?=?4), the pooled RR was 1.00 (95% CI?=?0.95–1.07; I²?=?17.3%; p_{heterogeneity}?=?0.305; Power?=?0.26) per additional live birth.

Conclusions: Our data identified little evidence suggesting that high parity is a protective factor against the development of NHL, including its B-cell and follicular subtypes.     

Safety of Prasugrel in Indian patients – Multicentric registry of 1000 cases

Background

Clopidogrel has been the only available antiplatelet drug used along with aspirin in patients of ACS. In recent years 2 new antiplatelet drugs (Prasugrel and Ticagrelor) have become available. Prasugrel in the dose of 10 mg OD has been found to be more efficacious but with increased risk of major bleeding. For this reason it has not gained widespread usage in ACS patients undergoing PCI. There are no systematic data on the use of Prasugrel in Indian population.

Method

This is a prospective, multicentric, hospital registry of 1000 patients with ACS undergoing PCI who were administered Prasugrel. The primary safety endpoint of this study was major and minor bleeding while the efficacy endpoint is the composite of CV death, nonfatal MI, nonfatal stroke up to 30 days after PCI. Patients with high bleeding risk were excluded.

Results

Most patients (91%) received loading dose of Prasugrel along with the maintenance dose getting according to the defined protocol. Patients were followed up to 30 days post procedure. Primary efficacy end point was reached in 3 patients only with two of them dying due to possible stent thrombosis and the third requiring revascularization of the target vessel for stent thrombosis. One major and 19 minor bleeding complications were recorded, with access site bleeding in 0.7% & non-access site bleeding in 1.2% of the subjects.

Conclusion

Prasugrel was found to be effective & not associated with a high incidence of bleeding in the high risk ACS patients when those at a high bleeding risk were excluded.