Monica Verdoia

Bivalirudin as compared to unfractionated heparin among patients undergoing coronary angioplasty - A meta-analyis of randomised trials

It has been shown that bleeding complications are associated with higher mortality rates among patients undergoing coronary angioplasty. Due to its properties, bivalirudin may provide benefits in terms of bleeding and thrombotic complications as compared to unfractionated heparin (UFH). The aim of the current study was to perform a meta-analysis of randomised trials to evaluate whether bivalirudin might offer benefits in terms of mortality as compared to UFH. We obtained results from all randomised trials evaluating the benefits of adjunctive bivalirudin as compared to UFH with or without Gp IIb-IIIa inhibitors among patients undergoing coronary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to October 2008. The following keywords were used: randomised trial, coronary angioplasty, stent, reperfusion, primary angioplasty, bivalirudin, direct thrombin inhibitors, hirulog. Primary endpoint was mortality. Secondary endpoint was infarction. Safety endpoint was the risk of major bleeding complications. No language restriction was applied. A total of nine randomised trials were included in the meta-analysis, with 15655 patients randomised to bivalirudin and 13104 patients randomised to UFH. We did not observe any difference in mortality between bivalirudin and UFH (1.73% vs 1.67%, p = 0.15) without any relationship between the baseline risk of mortality (r = 0.17, p = 0.71) or the reduction in major bleeding complications (r = -0.29, p = 0.53) and the benefits in mortality with bivalirudin. A trend in higher risk of myocardial infarction was observed with bivalirudin (6.9% vs 5.9%, p = 0.07, p het = 0.65). Bivalirudin was associated with a significant reduction in major bleeding complications (1.7% vs 3.4%, p < 0.0001), as compared to UFH. This meta-analysis shows that among patients undergoing coronary angioplasty, bivalirudin is associated with significant reduction in major bleeding complications. However, these benefits did not translate into benefits in mortality, with even a trend in higher risk of myocardial infarction.

Platelet distribution width and the extent of coronary artery disease: Results from a large prospective study

It has been postulated that large platelets may be an indicator of platelet activation, and thus be related to the extent of coronary artery disease (CAD). Platelet distribution width (PDW) directly measures the variability in platelet size. However, no data has been so far reported on this index and CAD. Thus, the aim of the current study was to investigate whether PDW is associated with the extent of CAD. We measured PDW in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least one coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. Patients with higher PDW were older (p = 0.012), with higher weight (p < 0.0001) and waist (p < 0.0001), larger prevalence of diabetes (p = 0.014), dilated cardiomyopathy or valvular heart disease (p < 0.0001) and less often family history of CAD (p = 0.021), more often on statins (p = 0.005), and diuretics (p = 0.016). PDW was significantly associated with baseline glycaemia (p = 0.002) and Red Blood Cell count (p < 0.0001), but inversely related to platelet count (p < 0.0001). PDW was not associated with the prevalence of coronary artery disease (OR [95% CI] = 0.91 [0.81–1.04], p = 0.16; adjusted OR [95% CI] = 0.96 [0.82–1.12], p = 0.56). No relationship was observed between IMT and PDW as tertiles or as continuous variable (Mean IMT: r = 0.04; p = 0.46; Maximal IMT: r = 0.036, p = 0.49). This study showed that PDW is not related to the extent of CAD and carotid IMT. Thus, PDW can not be considered as a risk factor for CAD.

Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: a meta-analysis of 8 randomized trials.

BACKGROUND Adjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty. METHODS We obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2-3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications. RESULTS A total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI]=1.76 [1.28-2.42], p<0.001), without significant benefits in terms of mortality (OR [95% CI]=0.85 [0.59-1.23], p=0.39), reinfarction (OR [95% CI]=0.79 [0.46-1.33], p=0.37), or major bleeding complications (OR [95% CI]=1.19 [0.76-1.87], p=0.44). However, we observed a significant relationship between patients risk profile and mortality benefits from IC abciximab administration (p=0.011). CONCLUSIONS The present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patients risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients.

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

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.

Ischaemic and bleeding complications with new, compared to standard, ADP-antagonist regimens in acute coronary syndromes: a meta-analysis of randomized trials

BACKGROUND Platelets play a pivotal role in the pathogenesis of acute coronary syndromes (ACS) and their inhibition remains a mainstay therapy in this setting. We aimed to perform a meta-analysis of randomized trials to evaluate the benefits of new oral antiplatelet regimens to block platelet ADP-receptors compared to standard-dose clopidogrel (300 mg loading dose followed by 75 mg/daily). METHODS We obtained results from all randomized trials enrolling patients with ACS. Primary endpoint was mortality. Secondary endpoints were myocardial infarction and definite in-stent thrombosis. Safety endpoint was the risk of major bleeding complications. We prespecified subanalyses according to new antiplatelet drugs (prasugrel/ticagrelor), high-dose clopidogrel (600 mg) and patients undergoing percutaneous coronary intervention. RESULTS A total of seven randomized trials were finally included in the meta-analysis (n = 58 591). We observed a significant reduction in mortality (2.9% vs. 3.4%, OR = 0.87, 95% CI 0.79-0.95, P = 0.002), recurrent myocardial infarction (4.2% vs. 5.2%, OR = 0.80, 95% CI 0.74-0.87, P < 0.0001), definite in-stent thrombosis (0.9% vs. 1.7%, OR = 0.52, 95% CI 0.43-0.63, P < 0.0001). The benefits in mortality and reinfarction were driven by the treatment with prasugrel or ticagrelor, without a significant difference in terms of major bleeding complications as compared to standard-dose clopidogrel (5% vs. 4.7%, OR = 1.06 95% CI 0.96-1.17, P = 0.25). CONCLUSION This meta-analysis showed that new oral antiplatelet regimens are associated with a significant reduction in mortality, reinfarction and in-stent thrombosis in ACS patients without an overall increase of major bleeding when treated with new antiplatelet drugs.

Aspirin desensitization in patients undergoing planned or urgent coronary stent implantation. A single-center experience

INTRODUCTION Dual antiplatelet therapy (aspirin and ADP-antagonists) is mandatory after stent implantation in order to avoid stent thrombosis, especially in the era of DES. In fact, a delayed re-endothelization process may enlarge the window of occurrence of stent thrombosis beyond 1-year after implantation. Allergy to acid acetylsalicylic is not a rare event and may influence the use and the choice of coronary stent with an important impact in terms of outcome especially in patients at high risk for in-stent restenosis. The aim of this study was to evaluate the safety and efficacy of a new intravenous rapid desensitization protocol in patients with acetylsalicylic acid sensitivity undergoing coronary stent implantation. METHODS Among a total of 1385 patients undergoing coronary angioplasty at our catheterization laboratory from January 2007 to June 2011, a total of 43 patients (3.1%) had history of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions). Twenty-three patients (53.5%) presented with acute coronary syndromes. All patients underwent a novel rapid desensitization procedure before or after cardiac catheterization (in case of ST-elevation myocardial infarctions, n=5). The desensitization procedure was based on intravenous administration of 9 sequential doses of aspirin (1, 2, 4, 8, 16, 32, 64, 128, 250 mg) over 4.5h without the use of corticosteroids or antihistamines. Patients were followed for at least 30 days and up to 12 months to assess compliance with aspirin therapy and adverse events. RESULTS The desensitization procedure was successful in 42 patients (97.6%). All patients underwent stent implantation (1.6 stents/patient). Drug-eluting stents were used in 36 patients (85.7%). At follow-up, all patients who successfully responded to the desensitization procedure did not develop any allergic reaction. CONCLUSIONS This study showed the safety and efficacy of a new rapid intravenous protocol desensitization for patients with history of aspirin sensitivity undergoing planned or urgent coronary stent implantation.

PlA(1)/PlA(2) polymorphism does not influence response to Gp IIb-IIIa inhibitors in patients undergoing coronary angioplasty

Glycoprotein IIb-IIIa (Gp IIb-IIIa), a fibrinogen receptor located on platelet surface, is a key point in the pathway leading to platelet aggregation. Therefore, great interest has emerged in the last decades on its pharmacological block, both by irreversible binding of abciximab or by competitive small molecules (tirofiban and eptifibatide). Gp IIb-IIIa inhibitors, in fact have demonstrated to provide benefits in clinical outcome among patients with acute myocardial infarction and in complex elective percutaneous coronary intervention (PCI) procedures. Still unclear is whether the genetic Leu 33Pro substitution in Gp IIIa may affect the extent of platelet aggregation inhibition by these drugs. Therefore, the aim was to evaluate whether this polymorphism (PlA) may influence inhibition of platelet aggregation after Gp IIb-IIIa administration in patients undergoing coronary angioplasty. We analyzed 80 patients undergoing nonurgent coronary revascularization and receiving Gp IIb-IIIa inhibitors (bolus and endovenous infusion; 40 patients with Abciximab and 40 patients with eptifibatide or tirofiban). The aggregation tests were performed at baseline and after 10 min, 1 h and 4 h, through multiplate impedance aggregometry. The PlA2 polymorphic variant was found in 26 patients (32.5%). The PlA2 carriers did not differ significantly from wild-type subjects for main clinical and angiographic features, except for in-stent restenosis that was more frequent among PlA2 carriers (P = 0.003). Therapy and aggregation values at baseline were similar in the two groups. The Leu33Pro substitution did not influence platelet response after Gp IIb-IIIa administration, which was confirmed for both abciximab and small molecules. This study showed that Leu33Pro polymorphism of Gp IIIa does not affect the extent of inhibition of platelet aggregation by Gp IIb-IIIa inhibitors.

Neutrophil to Lymphocyte Ratio and the Extent of Coronary Artery Disease: Results From a Large Cohort Study.

The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, may be of predictive and prognostic value for cardiovascular (CV) events. We evaluated the relationship of NLR with the prevalence and extent of coronary artery disease (CAD) in consecutive patients undergoing elective or urgent coronary angiography. Our population (n = 3738 patients) was divided into NLR quartiles. Higher NLR was associated with aging and established CV risk factors, previous percutaneous coronary revascularization, acute presentation, and more complex pharmacological therapy. The NLR was related to platelet count, white blood cell count, creatinine, glycemia, uric acid, and C-reactive protein (all P = .001) levels but inversely related to hemoglobin (P < .001), total cholesterol (P = .005), and triglycerides (P < .001) levels. The NLR was associated with multivessel disease (P < .001), anterior descending, right coronary arteries (P < .001) or circumflex branch lesions (P = .01), percentage of stenosis (P < .001), coronary calcification (P < .001), and intracoronary thrombus (P < .001) but inversely with in-stent restenosis (P < .001) and thrombolysis in myocardial infarction flow (P = .04). The NLR was directly related to the prevalence of CAD (P = .001) and severe CAD (P < .001). In patients undergoing coronary angiography, the NLR is independently associated with the prevalence and severity of CAD.

Mean platelet volume and the risk of periprocedural myocardial infarction in patients undergoing coronary angioplasty.

BACKGROUND Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI). Mean platelet volume (MPV) has been proposed as a marker for platelet activation, as larger sized platelets have been associated with higher pro-thrombotic risk. Therefore, aim of the current study was to evaluate whether MPV is associated with increased risk of PMI after PCI. METHODS We included 1056 consecutive patients undergoing PCI. We measured myonecrosis biomarkers at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined for troponin I increase by 3 times the ULN or by 50% if elevated at the time of the procedure. PMI was defined as CK-MB increase by 3 times the ULN or 50% if elevated at the time of the procedure. RESULTS We grouped patients according to tertiles values of MPV (<10.4 fl; 10.5-11.3 fl; >11.4 fl). High MPV was associated with diabetes (p = 0.025) and higher prevalence of cerebrovascular events (p = 0.005). MPV significantly related with haemoglobin levels (p < 0.001), but inversely to platelet count (p < 0.001) and higher presence of thrombus (p = 0.03). Larger sized platelets did not increase risk of periprocedural myonecrosis (p = 0.91; OR[95% CI] = 1.04[0.90-1.2], p = 0.64) or PMI (p = 0.09; OR[95%IC] = 1.13[0.93-1.37]; p = 0.20). Subgroup analysis confirmed no impact of MPV on periprocedural MI also in high-risk subsets of patients, such as those with ACS at presentation (OR[95%CI] = 1.09 [0.87-1.38]; p = 0.44), diabetes (OR[95% CI] = 1.02[0.71-1.47], p = 0.91), female gender (OR [95% CI] = 1.15 [0.78-1.71], p = 0.48), elderly patients (age ≥ 75 years) (OR[95%CI] = 1.21[0.87-1.69], p = 0.25) or with renal failure (OR[95%CI] = 1.55[0.91-2.61], p = 0.1). CONCLUSIONS This study demonstrates that MPV does not predict the risk of PMI in patients undergoing PCI.

Relation of Gender to Infarct Size in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty

Previous reports have shown that female gender is associated with impaired outcomes among patients with ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, mainly owing to a worst risk profile (more diabetes, more advanced age, and higher Killip class at presentation) compared to men. Still contrasting are data on the effect of gender on the outcome in patients with STEMI undergoing primary angioplasty. In particular, it is still unclear whether a larger infarct size might contribute to the explanation of the worse outcome in women. Therefore, the aim of the present study was to investigate gender-related differences in infarct size as evaluated by myocardial scintigraphy in a large cohort of patients with STEMI undergoing primary percutaneous coronary intervention. We included 830 patients with STEMI undergoing primary percutaneous coronary intervention. The infarct size was evaluated at 30 days using technetium-99m-sestamibi. A logistic regression analysis was performed to determine the relation between gender and infarct size (as percentage of patients above the median) after correction for baseline confounding factors. We also evaluated the presence of a potential age-gender interaction. A total of 183 patients (20.8%) were women. Female gender was associated with more advanced age and a greater prevalence of hypertension; previous infarction and smoking were more frequently observed in men. Female gender was associated with a smaller infarct size (p <0.001) that was confirmed after correction for baseline confounding factors (adjusted odds ratio 0.48, 95% confidence interval 0.33-0.7, p <0.001). No age-gender interaction was observed (p = 0.13). In conclusion, the results of the present study have shown that despite the presence of high-risk features at presentation, female gender was associated with a smaller infarct size than that in men, without any interaction between age and gender.