Impact of anticoagulation strategy with bivalirudin or heparin on nonaccess site bleeding in percutaneous coronary interventions: A meta-analysis of randomized trials.

BACKGROUND: Transradial approach has significantly decreased the rate of access site bleeding in patients undergoing percutaneous coronary interventions (PCI), therefore potentially mitigating the benefits offered by bivalirudin in lowering major bleeding complications as compared to heparin. However, nonaccess site bleeding, that represent the majority of hemorrhagic complications, still carry negative prognostic consequences for these patients and no study has so far defined the exact impact of bivalirudin on nonaccess site bleeding, that was therefore the aim of present meta-analysis. METHODS AND STUDY OUTCOMES: Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions were scanned comparing bivalirudin vs. heparin in patients undergoing PCI. Primary endpoint was the occurrence of nonaccess site bleeding within 30 days. Secondary endpoints were 30 days mortality and the occurrence of access-site bleeding. RESULTS: A total of nine randomized clinical trials were finally included, involving 32,587 patients, 55.8% randomized to bivalirudin. Bivalirudin significantly reduced the rate of nonaccess site bleeding (2.6 vs. 3.8%, OR [95% CI] = 0.68 [0.60-0.77], P < 0.00001, Phet = 0.10). However, the reduction of hemorrhagic events was more pronounced when bivalirudin was compared to heparin plus glycoprotein IIbIIIa inhibitors than when it was compared to heparin alone (r = -0.01 (-0.02; -0.001), P = 0.02). Similar results were observed for access-site bleeding (OR [95% CI] = 0.67 [0.57-0.79], P < 0.000001, Phet = 0.10), with a significant role of glycoprotein IIbIIIa inhibitors use (r = -0.02 (-0.04; -0.004), P = 0.017). Moreover, the observed benefits in hemorrhagic complications did not translate into mortality benefits (OR [95% CI] = 0.89 [0.76-1.05], P = 0.18; Phet = 0.12; r = 0.21 (-1.12; 1.53), P = 0.76). CONCLUSIONS: The present meta-analysis shows that bivalirudin can provide a significant reduction of both access and nonaccess site bleeding in patients undergoing PCI. However, these hemorrhagic benefits did not impact on survival, and moreover, were significantly conditioned by the association of heparin with potent antithrombotic strategies, such as glycoprotein IIbIIIa inhibitors, rather than by heparin or bivalirudin alone. Therefore, we could not provide any clinical evidence for the routine use of bivalirudin as preferred anticoagulation strategy for PCI. © 2017 Wiley Periodicals, Inc.

Risk and Benefits of Triple Therapy in Patients Undergoing Coronary Stent Implantation Requiring Oral Anticoagulation: A Meta-Analysis of 16 Studies.

BACKGROUND: Patients with coronary artery disease who undergo stent implantation and have concomitant indication for long-term oral anticoagulation represent a considerable proportion of the overall population. To date there is still no consensus about the optimal antithrombotic strategy to choose in this kind of patients, due to the difficult balance between an increased risk of bleeding and thromboembolic complications. Therefore, the aim of this study was to perform a meta-analysis to evaluate the risk and benefits of triple antithrombotic therapy versus dual antithrombotic therapy in patients undergoing coronary stent implantation, requiring long-term oral anticoagulation. METHODS: We performed formal searches of PubMed, EMBASE, Cochrane central register of controlled trials and major international scientific session abstracts from January 1990 to September 2015 regarding the use of triple antithrombotic therapy (TT) versus dual therapy (DT) in patients undergoing percutaneous coronary stent implantation that required chronic oral anticoagulation. Data regarding study design, inclusion/exclusion criteria, number of patients, and selected endpoints was extracted by 2 investigators. Disagreements were resolved by consensus. RESULTS: Sixteen trials with a total of 21716 patients undergoing coronary stent implantation with indication to long term oral anticoagulation, were finally included. A total of 6950 received TT, whereas 14766 received DT alone. The follow-up period ranged from 180 to 730 days. Data regarding mortality were available in 21658 patients (99.7 %). All cause mortality was observed in 10.4 % patients in TT versus 16.3 % in DT (OR [95 % CI] =0.73 [0.66-0.80], p <0.001; p het <0.001). In addition, TT was associated with a reduced incidence of MI (6.4 versus 9.8 %, OR [95 % CI] = 0.74 [0.65-0.84], p < 0.001; phet < 0.001) and ischemic stroke (1.8 versus 3.9 %, OR [95 % CI] = 0.55 [0.45-0.68], p < 0.001; p het = 0.07). As expected, TT was associated with a significant increase in major bleeding events (10.8 versus 8.5 %, OR [95 % CI] = 1.38 [1.25-1.53], p < 0.001; p het = 0.02). By meta regression analysis we found that benefits in mortality with TT were inversely related with the risk of bleedings (beta [95 % CI] = 2.25 (1.55; 2.95), p < 0.00001). The benefits with TT regarding overall mortality, recurrent MI and ischemic stroke were also confirmed in a pre-specified analysis versus DAPT or oral anticoagulation in association with a single antiplatelet agent. CONCLUSION: This meta-analysis showed that among patients undergoing coronary stent implantation, requiring chronic OAC, the use of a TT is associated with a significant reduction in overall mortality, recurrent MI and ischemic stroke. As expected, we found a higher incidence of bleedings in patients treated with triple therapy. The benefits in mortality were lost in patients at high-risk for bleedings.

Immature platelet fraction and high-on treatment platelet reactivity with ticagrelor in patients with acute coronary syndromes.

Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; ≥4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.

Impact of diabetes on immature platelets fraction and its relationship with platelet reactivity in patients receiving dual antiplatelet therapy.

Contrasting data have been reported so far on the role of reticulated platelets in suboptimal response to antiplatelet therapies. In particular, still unexplored is whether they may contribute to explain the higher risk of thrombotic complications observed in diabetic patients. Aim of the present study was to evaluate the impact of diabetes on the levels of reticulated platelets and its relationship with high residual on-treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy. In patients treated with ASA (100-160 mg) and clopidogrel (75 mg daily) or ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days post-discharge for an acute coronary syndrome or elective PCI. Aggregation was assessed by multiple-electrode aggregometry. We included 386 patients, 158 (40.9 %) diabetics. The percentage of IPF was similar in diabetic and non diabetic patients, both at baseline (3.5 ± 2.5 vs 3.6 ± 2.7 %, p = 0.91) and at 30-90 days re-assessment (3.3 ± 2.1 vs 3.5 ± 2.5 %, p = 0.30), with diabetes not emerging as an independent predictor of IPF above III tertile (adjusted OR [95 %CI] = 0.58 [0.30-1.09], p = 0.10). Diabetic patients displayed an enhanced platelet reactivity and a higher rate of HRPR with ADP antagonists (32.8 vs 22.5 %, p = 0.009). However, no association was found between the percentage of IPF and platelet function (r = -0.004; p = 0.95 for ASPI test, r = -0.04; p = 0.59 for ADP-mediated aggregation), or the rate of HRPR for ADP antagonsist across IPF tertiles. Results were similar for diabetics both receiving clopidogrel and ticagrelor. Diabetic patients display a higher platelet reactivity and suboptimal response to ADP-antagonists. However, the rate of reticulated platelets is neither influenced by diabetic status nor associated with an increased platelet reactivity among diabetic patients receiving dual antiplatelet therapy for a recent acute coronary syndrome or PCI.

Vitamin D levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

BACKGROUND: Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCIs). However, very few are known so far on the predictors of high-residual platelet reactivity (HRPR) despite antiplatelet strategies. Increasing attention has been paid in the last years to the role of vitamin D in atherothrombosis. Therefore, the aim of our study was to evaluate the impact of vitamin D levels on platelet function in patients treated with dual antiplatelet therapy (DAPT). Patients treated with DAPT (ASA and clopidogrel or ticagrelor) after a recent acute coronary syndrome (ACS) or elective PCI were scheduled for platelet function assessment at 30-90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®-Roche Diagnostics AG), HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values ≥417 AU*min (for ADP-antagonists). Fasting samples were obtained for main chemistry parameters and vitamin D level assessment. Our population is represented by 503 patients, who were divided according to vitamin D quartiles (≤9.1; 9.2-14.4; 14.5-21.7; >21.7 ng/ml). Lower vitamin D levels related with age (p = 0.04), diabetic status (p = 0.05), and previous coronary surgery (p = 0.007), therapy with beta-blockers and statins (p = 0.01 and p = 0.02). Vitamin D inversely related to the levels of total cholesterol (p = 0.01), triglycerides (p < 0.001), hemoglobin (p = 0.05), and HbA1c (p < 0.001). Significantly higher platelet reactivity was observed after platelet stimulation with ADP (p = 0.01), but not with other platelet activators. The prevalence of HRPR for ASA was low (1.2%) and not conditioned by Vitamin D levels (adjusted OR[95%CI] = 1.56[0.71-3.5], p = 0.27). HRPR with ADP-antagonists was observed in 26% of patients, and the rate increased with lower vitamin D quartiles (37.3% vs 22.2% vs 24.4% vs 20.2%, p = 0.005, adjusted OR[95%CI] = 1.23[1.02-1.49], p = 0.04). An absolute increase in HRPR with lower vitamin D levels was similarly observed among patients receiving ticagrelor (adjusted OR[95% CI] = 1.40[0.95-2.06], p = 0.08), and those on clopidogrel (adjusted OR[95%CI] = 1.31[0.99-1.75], p = 0.06). Thus, lower vitamin D levels are associated with higher platelet reactivity and impaired effectiveness of ADP-antagonists, while not influencing the effectiveness of ASA. Future studies will tell whether vitamin D supplementation can reduce platelet reactivity, overcoming the phenomenon of resistance to antiplatelet agents.

Impact of Diabetes on Homocysteine Levels and Its Relationship with Coronary Artery Disease: A Single-Centre Cohort Study.

BACKGROUND/AIMS: Coronary artery disease (CAD) is a major cause of mortality worldwide. Hyperhomocysteinemia has been identified as a risk factor for CAD due to increased thrombogenicity, oxidative stress status and endothelial dysfunction. Few data have been provided on the impact of diabetes on homocysteine and its relationship with the prevalence and extent of CAD in this high-risk subset of patients and therefore, this is the aim of this study. METHODS: Our population is represented by a consecutive cohort of patients undergoing coronary angiography at Azienda Ospedaliera-Universitaria, 'Maggiore della Carità', Novara, Italy from March 2007 to October 2012. RESULTS: Diabetes was observed in a total of 1,125 out of 3,534 patients. Diabetes was associated with more advanced age, hypercholesterolemia, arterial hypertension, renal failure, previous myocardial infarction, coronary revascularization (p < 0.001, respectively) and smoking (p = 0.001). Patients with diabetes were more frequently on angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-antagonists, diuretics, statins (p < 0.001, respectively), and acetylsalicylic acid (p = 0.004). Patients with diabetes displayed higher creatinine and triglycerides (p < 0.001), but lower total and high-density lipoprotein-cholesterol (p < 0.001) and haemoglobin (p < 0.001). Diabetes was associated with a significantly higher prevalence and extent of CAD and more complex lesions at angiography, including calcified lesion, total occlusions, in-stent restenosis. No significant difference was found in total homocysteine (tHcy) levels between diabetic and non-diabetic patients (p = 0.2). No difference in the percentage of patients with tHcy above the third tertile (≥18.2 nmol/ml) was observed between patients with or without diabetes (32.8 vs. 35%, p = 0.18; adjusted OR 0.88, 95% CI 0.73-1.05, p = 0.14). Among patients with diabetes, no significant association was found between tHcy, CAD (82.4 vs. 83.6 vs. 78.6%, p = 0.19) or severe CAD (33.2 vs. 33.1 vs. 36.9%, p = 0.18). Same results were observed after correction for baseline differences (adjusted OR 0.78, 95% CI 0.61-1.02, p = 0.11) for CAD and severe CAD (adjusted OR 0.92, 95% CI 0.76-1.13, p = 0.46). CONCLUSIONS: In our study, diabetes was not associated with higher tHcy levels. Furthermore, elevated tHcy is not a risk factor for CAD among patients with diabetes.

Effect of diabetes mellitus on periprocedural myocardial infarction in patients undergoing coronary stent implantation.

BACKGROUND: Diabetic patients undergoing percutaneous coronary interventions are still regarded as a very high risk category because of an increased platelet reactivity and risk of complications, especially in patients with inadequate glycaemic control. However, although its prognostic effect on long-term outcome is well-defined, still unclear is the effect of diabetes on the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary interventions, which was therefore the aim of our study. METHODS: Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after nonemergent percutaneous coronary interventions. Periprocedural myocardial infarction was defined as creatine kinase-MB increase by three times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as troponin I increase by three times the upper limit normal or 50% of baseline. RESULTS: Of 1311 patients, diabetes mellitus was found in 458 patients (34.9%) and associated with age (p = 0.03), hypertension (p < 0.001), renal failure (p = 0.01), previous MI (p = 0.03), previous coronary revascularization (p < 0.001), higher fasting glycaemia and lower haemoglobin (p < 0.001), more severe coronary disease (p < 0.001), multivessel percutaneous coronary interventions (p = 0.03), coronary calcification (p = 0.003) and in-stent restenosis (p < 0.001) but lower presence of thrombus (p = 0.03). Diabetic patients were receiving significantly more frequent specific pharmacological treatment at admission. Diabetic status did not influence the risk of periprocedural myocardial infarction or periprocedural myonecrosis [adjusted OR(95%CI) = 0.90(0.64-1.27), p = 0.57 and adjusted OR(95%CI) = 0.92(0.70-1.21), p = 0.55]. Amongst diabetic patients, we did not observe any effect of chronic glycaemic control on periprocedural myocardial infarction. CONCLUSIONS: Diabetic status, independent of chronic glycaemic control, is not associated with increased risk of periprocedural myocardial infarction and myonecrosis in patients undergoing percutaneous coronary interventions.

Body Mass Index and Platelet Reactivity During Dual Antiplatelet Therapy With Clopidogrel or Ticagrelor.

INTRODUCTION: Dual antiplatelet therapy (DAPT) is considered essential in clinical management of patients undergoing percutaneous coronary revascularization or acute coronary syndromes. However, the optimal platelet inhibition is not always obtained, with high residual platelet reactivity (HRPR) increasing stent thrombosis and recurrent ischemic events. Aim of this study was to investigate the impact of body mass index (BMI) on platelet reactivity in patients on DAPT. METHODS: We included patients treated with acetylsalycilic acid (ASA) (100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day) for acute coronary syndromes or drug-eluting stent implantation. Platelet reactivity was assessed at 30-90 days postdischarge by multiple-electrode aggregometry. HRPR for adenosine diphosphate (ADP) antagonists was defined as ADP test results >417 AU*min. HRPR for ASA was considered for ASPI test >862 AU*min. RESULTS: Our population is represented by 498 patients, 308 (61.8%) were treated with clopidogrel and 190 (38.2%) with ticagrelor. Overall, higher BMI was related with younger age (P = 0.003), higher prevalence of diabetes mellitus (P < 0.001), hypercholesterolemia (P = 0.017), hypertension (P < 0.001), chronic therapy with angiotensin-receptor blockers (P = 0.019), calcium channel blockers (P = 0.003). Higher values of BMI directly related with hemoglobin (P = 0.02), triglycerides (P < 0.001), glycemia (P = 0.035), HbA1c (P < 0.001), and inversely related with high-density lipoprotein cholesterol (P = 0.01). BMI did not influence the effectiveness of ASA, whereas it was associated to a nonsignificant trend for higher platelet reactivity (r = 0.08, P = 0.08) for ADP antagonists. In fact, 111 patients (22.3%) displayed HRPR at ADP test (>417 AU*min) with no statistically significant difference according to BMI {20.3% vs. 27.1% vs. 25.7%, P = 0.28; adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.19 [0.86-1.64], P = 0.30}. However, results were different when considering separately patients receiving clopidogrel or ticagrelor. In the clopidogrel-treated subgroup, significantly higher ADP-mediated aggregation values were found in patients with higher BMI (r = 0.14, P = 0.023) that emerged as an independent predictor of HRPR with clopidogrel [OR (95% CI), 1.45 (1.01-2.12), P = 0.049]. On the contrary, no impact of BMI was observed in the ticagrelor-treated subgroup for platelet reactivity (r = -0.036, P = 0.62) or the prevalence of HRPR [adjusted OR (95% CI), 0.73 (0.39-1.36), P = 0.32]. CONCLUSIONS: This study shows that among patients treated with DAPT for coronary artery disease, higher BMI is related to increased platelet reactivity and a higher prevalence of HRPR in clopidogrel-treated patients while not significantly influencing the effectiveness of ticagrelor or ASA.

Homocysteine Levels Influence Platelet Reactivity in Coronary Artery Disease Patients Treated With Acetylsalicylic Acid.

BACKGROUND: Suboptimal platelet inhibition with antiplatelet treatments is associated with a severe prognosis in patients with coronary artery disease (CAD), and the identification of its determinants is still challenging. Homocysteine elevation has emerged as a prothrombotic factor, influencing coagulative status and endothelial function and potentially modulating platelet aggregation. We therefore aimed to evaluate the effects of homocysteine (Hcy) levels on platelet reactivity in patients receiving acetylsalicylic acid (ASA) with or without ADP antagonists. METHODS: Patients undergoing coronary angiography and receiving ASA (100-160 mg daily) for >7 days, with or without ADP antagonists, were included. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition was defined as on-treatment aggregation above the lower limit of normality. RESULTS: Our population is represented by 508 ASA-treated patients, 406 (80.1%) of whom on dual antiplatelet therapy (ASA and ADP antagonists). Hcy levels above the median (15.1 nmol/mL) were associated with male gender (P = 0.04), hypertension (P = 0.004), hypercholesterolemia (P = 0.03), aging, renal failure (P < 0.001, respectively), previous coronary bypass grafting (P = 0.04), therapy with calcium antagonists (P = 0.04) and diuretics (P = 0.001), and multivessel CAD (P = 0.03). Higher Hcy is directly related with serum creatinine and uric acid (P < 0.001). Suboptimal platelet inhibition was found in 16 patients (3.2%) for ASA and for ADP antagonists in 80 patients (19.7%). Hcy levels significantly affected suboptimal response to ASA, but not to ADP-mediated aggregation. In fact, a linear relationship was found between homocysteine and platelet reactivity after stimulation with arachidonic acid (r = 0.14, P = 0.004) and collagen (r = 0.12, P = 0.02), but not with ADP (r = 0.02, P = 0.77). Moreover, after correction for baseline differences, Hcy above the median was confirmed as an independent predictor of impaired ASA response [adjusted odds ratio (95% confidence interval) = 3.7 (1.08-12.4), P = 0.04]. CONCLUSIONS: Among patients with CAD, elevated homocysteine is an independent predictor of suboptimal response to ASA, but not to ADP antagonists.

Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual Antiplatelet Therapy.

BACKGROUND: Low response to antiplatelet agents has been associated to an increased risk of thrombotic complications and recurrent ischemic events. Platelet size has been proposed as a potential marker of platelet reactivity. Therefore, the aim of the present study was to evaluate the impact of platelet Larger Cell Ratio (p-LCR) on platelet aggregation and the prevalence of residual high-on treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy (DAPT) after a recent acute coronary syndrome or coronary revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. HRPR was considered for ASPI test >862 AU*min (for ASA) or ADP test values ≥417 AU*min (for ADP-antagonists) using impedance aggregometry. RESULTS: Our population consisted of 530 patients receiving DAPT, who were divided in tertiles according to values of p-LCR (< 27.6; 27.6-34.7; ≥34.7 l). p-LCR was related with use of beta-blockers (p = 0.02) and statins (p = 0.002), and inversely with acute presentation (p = 0.05). Higher platelet count (p < 0.001) and haemoglobin levels (p = 0.001) were observed in higher p-LCR tertiles. The prevalence of HRPR for ASA was low and not significantly different across tertiles of p-LCR (1.1 vs 1.1 vs 1.7%, p = 0.66; adjusted OR[95%CI] = 1.68[0.66-4.29], p = 0.27). Moreover, p-LCR did not influence the occurrence of HRPR for ADP-antagonists (24.4% vs 20.9% vs 25.6 %%, p = 0.80, adjusted OR[95%CI] = 0.88[0.67-1.17], p = 0.38) and similar results were obtained when considering separately patients receiving clopidogrel (adjusted OR[95%CI] = 1.21[0.86-1.69], p = 0.29) or ticagrelor (adjusted OR[95%CI] = 1.17[0.69-2], p = 0.56). CONCLUSION: In patients receiving DAPT for coronary artery disease, p-LCR does not impact platelet reactivity. Larger platelets did not influence the prevalence of high-on treatment platelet reactivity with the antiplatelet agents ASA, clopidogrel or ticagrelor.

Absolute eosinophils count and the extent of coronary artery disease: a single centre cohort study.

Leukocytes have been involved in the pathogenesis of atherosclerosis, and recent attention has been raised on eosinophils, that have been claimed for a wide number of cardiovascular pathologies, affecting endocardium, myocardium and vascular walls. However, few data have been reported so far on the relationship between absolute eosinophils count (AEC) and the prevalence and extent of coronary artery disease (CAD), that was the aim of present study. Consecutive patients undergoing non-urgent coronary angiography were included. Haematological parameters were measured at admission. Significant CAD was defined as at least 1 vessel stenosis >50 %, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Our population is represented by 3,742 patients, divided according to tertiles values of AEC (≤0.1; 0.1-0.2; >0.2 × 10(3)/µl). Higher eosinophils values were significantly associated to male gender, main established cardiovascular risk factors, previous percutaneous or surgical coronary revascularization, antihypertensive and antiplatelet therapy at admission but inversely with acute presentation. Higher AEC was directly related with platelets count (p < 0.001), haemoglobin levels (p = 0.02), white blood cells count (p = 0.02), higher serum creatinine (p < 0.001), triglycerides (p < 0.001) and glycosylated haemoglobin (p < 0.001), while inversely with HDL cholesterol (p < 0.001). AEC was associated with multivessel disease (p = 0.03), chronic occlusions (p = 0.01), in-stent restenosis (p = 0.002), while inversely with the presence of intracoronary thrombus (p < 0.001). A significant relationship was found between AEC and the prevalence of coronary artery disease (p = 0.049), but not for the extent of more severe LM/trivessel CAD (p = 0.31). At multivariate analysis no independent role of eosinophils was found for CAD (adjusted OR [95 % CI] = 1.02 [0.91-1.15], p = 0.70), or severe CAD (adjusted OR [95 % CI] = 0.99 [0.89-1.1], p = 0.9), even when considering separately acute and elective patients. In conclusion, among patients undergoing coronary angiography, higher eosinophils levels are not independently associated with the prevalence and extent of coronary artery disease, but appear confounded by their link with major cardiovascular risk factors.

Impact of red blood cells count on the relationship between high density lipoproteins and the prevalence and extent of coronary artery disease: a single centre study [corrected].

We have hypothesized that high red blood cells (RBC) count can potentially play an atheroprotective role in patients with coronary atherosclerosis. We, therefore, have investigated the relationship between high density lipoproteins cholesterol (HDL-C) and RBC levels in patients undergoing coronary angiography. Coronary artery disease (CAD) is a major cause of mortality. Impaired lipid profile represents a major risk factor for atherosclerosis. High density lipoprotein (HDL) is a key factor in atherosclerosis disease development. RBC can mimic HDL's reverse cholesterol transportation with a potential atheroprotective role. Coronary angiography has been evaluated in 3,534 patients. Fasting samples were collected for haematology and lipids levels assessment. Coronary disease was defined for at least 1 vessel stenosis >50 %. Patients were divided according to HDL-C and RBC tertiles. Lower HDL-C was significantly associated to the prevalence of CAD (84.8 vs 78.5 vs 67.3 %, p ≤ 0.001; adjusted OR [95 % CI] = 1.55 [1.3-1.8], p < 0.001) and severe CAD (30 % vs 30 % vs 24.4 %, p = 0.002; adjusted OR [95 % CI] = 1.08 [1.01-1.16], p = 0.02), this relationship was maintained even dividing our population according to RBC tertiles (p < 0.001).In conclusion, HDL-C levels are directly related to RBC count and inversely to the prevalence and extent of coronary disease. Higher RBC levels can reduce the risk of CAD in patients with lower HDL-C levels, suggesting an important atheroprotective role.

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-PlA(1)/PlA(2) 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 PlA(2) polymorphism, 163 of them in homozygosis. Angiographically defined CAD was present in 3573 (74.3%) PlA(1)/PlA(1) patients and in 1430 (75.5%) PlA(2) carriers. PlA(2) polymorphism was not associated with an increased prevalence of coronary artery disease, (OR [95% CI] = 1.07 [0.95-1.21], p = 0.28, pheterogeneity = 0.39). Similar results were obtained for multivessel disease (OR [95% CI] = 1.07[0.95-1.20], p = 0.27, pheterogeneity = 0.12). Meta-regression analysis demonstrated a significant inverse relationship between the risk of CAD among the PlA(2) 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.

Platelet-larger cell ratio and the risk of periprocedural myocardial infarction after percutaneous coronary revascularization.

Periprocedural myocardial infarction (PMI) represents a frequent complication in patients undergoing percutaneous coronary revascularization. Despite great attention focused on pharmacological prevention of periprocedural damage, very little is known about using biomarkers to potentially predict the risk of PMI. Larger platelets have been associated with enhanced reactivity, increased cardiovascular risk, and higher rates of complications after coronary stenting. The platelet-larger cell ratio (P-LCR) identifies the largest-sized fraction of platelets, the proportion potentially more closely related to thrombotic events. The present study evaluated the relationship between P-LCR and PMI. We included 1,285 patients undergoing PCI. Myonecrosis biomarkers were dosed at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I increase by three times the upper limit of normal (ULN) or by 50 % of an elevated baseline value, whereas PMI was defined as an increase in creatine kinase MB by 3 × ULN or 50 % of baseline. We grouped patients according to tertile values of P-LCR (<27.5; ≥35.1). Higher P-LCR was associated with age (P = 0.01), diabetes (P = 0.001), previous cerebrovascular accidents (P = 0.007), therapy with statins (P < 0.001), angiotensin receptor blockers (P < 0.001), aspirin (P = 0.002), and nitrates (P = 0.01). P-LCR was related to hemoglobin levels (P < 0.001), and inversely related to platelet count (P < 0.001) and glycemia (P = 0.05). Patients with higher P-LCR had a lower presence of coronary thrombus (P = 0.003). Higher P-LCR values did not increase the risk of PMI (P = 0.10; adjusted odds ratio (OR) (95 % confidence interval (CI)) = 0.97 (0.69-1.38)), P = 0.89) or periprocedural myonecrosis (P = 0.96; adjusted OR (95 % CI) = 1.003 (0.76-1.32), P = 0.99). Results were confirmed even in higher-risk subgroups of patients. P-LCR does not increase the risk of periprocedural myocardial infarction and myonecrosis in patients undergoing coronary stenting.

Vitamin D deficiency is independently associated with the extent of coronary artery disease.

BACKGROUND: Vitamin D (25-OH D3) deficiency represents a rising social and economic problem in Western countries. Vitamin D has been recently reported to modulate inflammatory processes, endothelium and smooth muscle cell proliferation and even platelet function, thus potentially modulating atherothrombosis. Great interest has been addressed on its impact on cardiovascular outcome, with contrasting results. The aim of current study was to evaluate the relationship between 25-OH D3 and the extent of coronary artery disease (CAD) in a consecutive cohort of patients undergoing coronary angiography. MATERIALS AND METHODS: Patients undergoing elective coronary angiography were included in a cross-sectional study. Fasting samples were collected for 25-OH D3 levels assessment. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or trivessel disease, as evaluated by quantitative coronary angiography. RESULTS: Hypovitaminosis D was observed in 70·4% of 1484 patients. Patients were divided according to vitamin D tertiles (< 9·6; 9·6-18·4; ≥ 18·4). Lower vitamin D levels were associated with age, female gender (P < 0·001), renal failure (P = 0·05), active smoking (P = 0·001), acute coronary syndrome at presentation (P < 0·001), therapy with calcium antagonists (P = 0·02) and diuretics (P < 0·001), less beta-blockers (P = 0·02) and statins (P = 0·001) use. Vitamin D was directly related to haemoglobin (P < 0·001) and inversely with platelet count (P = 0·002), total and low-density-lipoprotein cholesterol (P = 0·002 and P < 0·001) and triglycerides (P = 0·01). Vitamin D did not influence angiographic features of coronary lesions, but was associated with higher prevalence of left main or right CAD (P = 0·03). Vitamin D deficiency was significantly associated with higher prevalence of CAD (adjusted OR [95%CI] = 1·32[1·1-1·6], P = 0·004) and severe CAD (adjusted OR [95%CI] = 1·18[1-1·39], P = 0·05). CONCLUSION: Hypovitaminosis D was observed in the vast majority of patients undergoing coronary angiography. Vitamin D deficiency is significantly associated with the prevalence and extent of CAD, especially for patients with values < 10 ng/mL. Therefore, future large studies are needed to evaluate whether vitamin D supplementation may prevent CAD and its progression.

Uric acid and risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention.

BACKGROUND: Periprocedural myocardial infarction still occurs in patients undergoing percutaneous coronary intervention. However, very little is known about the role of biomarkers possibly predicting this complication. Serum uric acid has been associated with enhanced inflammatory status, higher thrombotic risk and poorer outcome after percutaneous coronary intervention. We therefore, evaluated the association between uric acid levels and periprocedural myocardial infarction in patients undergoing percutaneous coronary intervention. METHODS: We evaluated 1272 consecutive patients undergoing percutaneous coronary intervention. We measured myonecrosis biomarkers at intervals from 8 to 48 h after percutaneous coronary intervention. Periprocedural myonecrosis was defined as a troponin I increase by 3 times the upper limit normal (ULN) or by 50% of an elevated baseline value and periprocedural myocardial infarction as creatine kinase-Myocardial Band increase by 3 times the ULN or 50% of baseline. RESULTS: Patients were divided according to tertile values of uric acid (< 5.40, ≥ 6.70 mg/dL). Serum uric acid was related to age, male gender, hypertension, smoking, renal failure (p < 0.001), previous coronary artery bypass grafts (p = 0.05), therapy with ACE inhibitors (p = 0.001) and diuretics (p < 0.001), glycaemia (p = 0.001), creatinine (p < 0.001), haemoglobin (p = 0.002) and white blood cells (p = 0.02). Serum uric acid was inversely related to type C lesions (p = 0.03) and coronary thrombus (p = 0.02). SUA did not affect the risk of periprocedural myocardial infarction (p = 0.29; adjusted odds ratio = 1.11[0.93-1.32], p = 0.26) or periprocedural myonecrosis (p = 0.97; adjusted odds ratio = 0.99[0.86-1.14], p = 0.89). Results were confirmed at subgroup analyses of higher-risk subsets of patients. CONCLUSION: This is the first large study showing that serum uric acid is not associated with an increase in the risk of periprocedural myocardial infarction in patients undergoing percutaneous coronary revascularization.

Benefits from new ADP antagonists as compared with clopidogrel in patients with stable angina or acute coronary syndrome undergoing invasive management: a meta-analysis of randomized trials.

AIMS: New P2Y12 receptor inhibitors have provided new and more potent antiplatelet strategies, although raising several concerns on possible increase of bleedings. The aim of current meta-analysis was to evaluate the efficacy and safety of new adenosine diphosphate (ADP) receptor antagonists as compared with clopidogrel in elective or ACS patients managed invasively. METHODS AND RESULTS: Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions abstracts were scanned for randomized trials comparing new ADP antagonists with clopidogrel in patients with acute coronary syndromes or stable angina. Primary endpoint was mortality. Secondary endpoints were: (1) nonfatal myocardial infarction (MI), (2) recurrent ischemia symptoms or ischemia-driven revascularization (RI/IDR), (3) stent thrombosis (ST), and (4) safety endpoints, defined as for TIMI major bleeding criteria. A total of 8 randomized clinical trials were finally included, for a total population of 67,851 patients. Mean follow-up was 7.6 months, ranging from 48 hours to 30 months. New ADP antagonists significantly reduced mortality {3.1% vs. 3.6%, odds ratio [OR] [95% confidence interval (CI)], 0.86 [0.79-0.94], P = 0.0008, P(het) = 0.18}, with greater impact of oral drugs. Similar benefits were found for MI [6.1% vs. 7%; OR (95% CI) (random-effect model) = 0.88 (0.79-0.98), P = 0.01, P(het) = 0.02], RI [2.7% vs. 3.1%; OR (95% CI) = 0.85 (0.77-0.93), P = 0.0005, P(het) = 0.09], or ST [1.1% vs. 1.7%; OR (95% CI) = 0.60 (0.51-0.71), P < 0.00001, P(het) = 0.13]. By meta-regression analysis, no relationship was observed between benefits in mortality, new MI, RI, and ST with new ADP antagonists and patients' risk profile [beta (95% CI) = -0.01 [-0.30 to 0.27], P = 0.94; beta (95% CI) = -0.05 [-1.49 to 1.43], P = 0.96); beta (95% CI) = 0.19 (-0.18 to 0.57), P = 0.31, and beta (95% CI) = -0.08 (-0.86 to 0.70), P = 0.84, respectively]. CONCLUSIONS: Present meta-analysis shows that the new ADP antagonists prasugrel, ticagrelor, and cangrelor are associated to significant reduction of mortality, reinfarction, RI, and ST respect to clopidogrel alone, without significant increase in bleeding complications.

Switching from high-dose clopidogrel to prasugrel in ACS patients undergoing PCI: a single-center experience.

Prasugrel has been shown to be superior to clopidogrel in the setting of ACS patients undergoing coronary angioplasty. However, few data have been reported so far on those patients who switch from clopidogrel to prasugrel after coronary angioplasty. Aim of the current study was to evaluate the safety of prasugrel loading dose administration in ACS patients undergoing PCI and pretreated with high-dose clopidogrel. From May 2010 to December 2011 150 ACS patients undergoing coronary angioplasty and pretreated with high-dose clopidogrel, were switched to prasugrel loading dose soon after the procedure. They were matched (ratio 1:2) according to sex and age with a group of 300 ACS patients undergoing angioplasty and treated with high-dose clopidogrel only from May 2010 to December 2011. All demographic clinical and angiographic were collected. Primary endpoint was the rate of major bleeding complications (according to ACUITY trial definition) at 30-day follow-up. Secondary endpoints were: TIMI major and minor bleeding, definite stent thrombosis, major adverse cardiac events (MACE) and Net adverse cardiac events (NACE) at 30-day followup. The two groups of patients showed similar baseline demographic, and clinical characteristics. Most of the patients had unstable angina or non-ST segment elevation myocardial infarction. Almost (about 95 %) all patients underwent radial approach. No difference was observed in major bleeding complications according to both ACUITY (2.0 vs 2.0 %) and TIMI Major (0.7 vs 1.3 %) definition. No difference between the two groups was observed in terms of in-stent thrombosis, MACE and NACE at 30-day follow-up. Our observational study showed that switching to prasugrel with loading dose soon after angioplasty among ACS patients who were pretreated with clopidogrel seems to be well tolerated without overt evidence of heightened major bleeding. Future large randomized trials are certainly needed to confirm these findings.

The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials.

Contrast induced nephropathy (CIN) is a common complication of coronary angiography/angioplasty. Prevention is the key to reduce the incidence of CIN and it begins with appropriate pre-procedural management. Statins have been shown to possess pleiotropic effects (anti-oxidant, anti-inflammatory and anti-thrombotic properties) and their effects on CIN were assessed in several studies with conflicting results. Aim of this meta-analysis is to evaluate the efficacy of short-term statins for the prevention of CIN in patients undergoing coronary angiography/percutaneous interventions. We performed formal searches of PubMed, EMBASE, Cochrane central register of controlled trials and major international scientific session abstracts from January 1990 to January 2014 of trials which compares short-term statins versus Placebo for the prevention of CIN in patients undergoing coronary angiography/angioplasty. Data regarding study design, statin dose, inclusion/exclusion criteria, number of patients, and clinical outcome was extracted by 2 investigators. Eight trials were included, with a total of 4734 patients. CIN occurred in 79/2,358 patients (3.3%) treated with statins versus 153/2,376 patients (6.4%) of the placebo group [OR 95% CI 0.50 (0.38-0.66), p < 0.00001; p het = 0.39]. Benefits were both observed with high-dose short-term statins [OR 95% CI 0.44 (0.30-0.65), p < 0.0001; p het = 0.16] and low-dose statins, [OR 95% CI 0.58 (0.39-0.88), p = 0.010; p het = 0.90]. By meta-regression analysis, no significant relationship was observed between benefits from statin therapy and patient's risk profile (p = 0.26), LDL cholesterol (p = 0.4), contrast volume (p = 0.94) or diabetes rate (p = 0.38). This meta-analysis showed that among patients undergoing coronary angiography/percutaneous intervention the use of short-term statins reduces the incidence of CIN, and therefore is highly recommended even in patients with low LDL-cholesterol levels.