A. Schaffer

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.

Comprehensive meta-analysis of radial vs femoral approach in primary angioplasty for STEMI.

INTRODUCTIONnPrimary angioplasty has improved survival as compared to thrormbolysis. However, bleeding complications still represent the Achilles heel, mainly related to access site. Although the radial approach is getting larger consensus for elective percutaneous procedures, its safety and advantages in the setting of ST-segment elevation (STEMI) is controversial. Therefore, the aim of the current study was to perform a comprehensive meta-analysis of randomized and non randomized trials comparing radial vs transfemoral approach in primary angioplasty for STEMI.nnnMETHODSnThe literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to October 2012. No language restrictions were enforced.nnnRESULTSnA total of 27 trials were finally included, with 29,194 patients (4685 enrolled in 11 randomized trials and 24,509 in 15 non randomized trials). A total of 10,052 patients underwent radial approach and 19,142 patients underwent femoral approach. A total of 2499 patients (8.6%) had died at follow-up. Radial approach was associated with a significant reduction in short-term mortality (5.2% vs 10.3%, OR [95% CI]=0.55 [0.40, 0.76], p<0.001, p het=0.97) (primary endpoint). Significant benefits were observed in both randomized (2.7% vs 4.7%, OR [95% CI]=0.55 [0.40, 0.76], p<0.001, p het=0.97) and observational studies (5.9% vs 11.1%, OR [95% CI]=0.48 [0.43, 0.54, p<0.001, p het=0.44]). Major bleeding complications were observed in a total of 808 patients (2.8%). Radial approach was associated with a significant reduction in major bleeding complications as compared to femoral approach (1.9% vs 4.7%, OR [95% CI]=0.38 [0.31, 0.47], p<0.0001, p het=0.17), similarly in both randomized (2.7% vs 5%, OR [95% CI]=0.51 [0.37, 0.70], p<0.001, p het=0.87) and observational studies (1.4% vs 4.6%, OR [95% CI]=0.32 [0.25, 0.42], p<0.0001, p het=0.32). Both benefits in death and major bleeding complications were not related to baseline risk profile.nnnCONCLUSIONSnThis meta-analysis of randomized and non-randomized trials showed that among STEMI patients undergoing primary angioplasty the radial approach is associated with a consistent reduction in mortality and major bleeding complications and. Therefore, routine use of radial approach should be strongly encouraged in primary angioplasty.

High fibrinogen level is an independent predictor of presence and extent of coronary artery disease among Italian population

Few reports have so far investigated the relationship between fibrinogen levels and the extent of coronary artery disease (CAD) as evaluated by coronary angiography, that is therefore the aim of the current study. We measured fibrinogen in 2,121 consecutive patients undergoing coronary angiography. Patients were divided in 5 groups based on quintiles of fibrinogen levels. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured carotid intima-media thickness (CIMT) in a subgroup of 359 patients. Patients with elevated fibrinogen were older (Pxa0=xa00.038), with larger prevalence of diabetes (Pxa0=xa00.027), female gender (P < 0.0001), hypertension (P < 0.001), chronic renal failure (P < 0.0001), previous CVA (Pxa0=xa00.036), less often with family history of CAD (Pxa0=xa00.019) and previous PCI (P < 0.0001), more often presenting with ACS (P < 0.0001), more often on nitrates (P < 0.0001), clopidogrel (Pxa0=xa00.009) and diuretics (P < 0.0001). Fibrinogen levels were linearly associated with baseline glycaemia (P < 0.017), WBC count (P < 0.0001), creatinine (P < 0.0001), and Platelet count (P < 0.0001) but inversely associated with RBC count (P < 0.0001). Fibrinogen levels were associated with CAD (Pxa0=xa00.001), especially for extremely high levels (5th percentile, P < 0.0001). At multivariate analysis, after correction for baseline confounding factors, high fibrinogen level (5th percentile) was still associated with the prevalence of CAD (Pxa0=xa00.034). Furthermore, fibrinogen levels were related with maximal CIMT (rxa0=xa00.12; Pxa0=xa00.01), with larger prevalence of carotid plaques in patients with higher fibrinogen levels (5th quintile) as compared to remaining patients (Pxa0=xa00.046). This study showed that high fibrinogen level is significantly associated with CAD and carotid atherosclerosis.

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

BACKGROUNDnPlatelets 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 (300u2009mg loading dose followed by 75u2009mg/daily).nnnMETHODSnWe 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 (600u2009mg) and patients undergoing percutaneous coronary intervention.nnnRESULTSnA total of seven randomized trials were finally included in the meta-analysis (nu2009=u200958u2009591). We observed a significant reduction in mortality (2.9% vs. 3.4%, ORu2009=u20090.87, 95% CI 0.79-0.95, Pu2009=u20090.002), recurrent myocardial infarction (4.2% vs. 5.2%, ORu2009=u20090.80, 95% CI 0.74-0.87, Pu2009<u20090.0001), definite in-stent thrombosis (0.9% vs. 1.7%, ORu2009=u20090.52, 95% CI 0.43-0.63, Pu2009<u20090.0001). 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%, ORu2009=u20091.06 95% CI 0.96-1.17, Pu2009=u20090.25).nnnCONCLUSIONnThis 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

INTRODUCTIONnDual 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.nnnMETHODSnAmong 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThis 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 10u200amin, 1u200ah and 4u200ah, 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 (Pu200a=u200a0.003). 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.

Impact of gender difference on vitamin D status and its relationship with the extent of coronary artery disease

BACKGROUND AND AIMnThere has been a surge of interest in the cardiovascular effects of vitamin D (25(OH)D), preventing the processes leading to vascular wall degeneration and coronary artery disease (CAD). Gender differences have been suggested for vitamin D status, with a higher rate of deficiency occurring especially in post-menopausal women, increasing the risk of bone fractures and osteoporosis. However, to date, few studies have evaluated the differences in 25(OH)D levels according to gender and their impact on the extent of CAD, which was therefore the aim of the present study.nnnMETHODS AND RESULTSnIn patients undergoing coronary angiography, fasting samples were collected for the assessment of 25(OH)D levels. Significant CAD was defined as at least one vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. Of the 1811 patients included, 530 (29.3%) were females, who displayed older age (pxa0<xa00.001), higher rate of renal failure (pxa0<xa00.001), hypertension (pxa0=xa00.05), treatment with angiotensin-receptor blockers (pxa0=xa00.03) and diuretics (pxa0<xa00.001), acute presentation (pxa0<xa00.001), higher platelet count (pxa0<xa00.001), glycosylated haemoglobin (pxa0=xa00.02) and cholesterol (pxa0=xa00.001), but an inverse relationship with smoking (pxa0<xa00.001), previous cardiovascular events (pxa0<xa00.001), treatment with statins and acetylsalicylic acid (ASA) (pxa0<xa00.001), body mass index (pxa0=xa00.002), haemoglobin (pxa0<xa00.001), leucocytes (pxa0=xa00.03) and triglycerides (pxa0<xa00.001). Female gender was associated with lower vitamin D levelsxa0(14.5xa0±xa010.9 vs. 15.9xa0±xa09.5, pxa0=xa00.007) and independently associated with severe vitamin D deficiency (41.9% vs. 30.4%, pxa0<xa00.001; adjusted odds ratio (OR) (95% confidence interval (CI))xa0=xa01.42 (1.08-1.87), pxa0=xa00.01). Lower tertiles of vitamin D were associated with an increased prevalence and severity of CAD in females (adjusted OR (95% CIxa0=xa01.26 (1.10-1.44), pxa0=xa00.001 for CAD; adjusted OR (95% CI)xa0=xa01.6 (1.39-1.87), pxa0<xa00.001 for severe CAD). In males, vitamin D status was independently related to the prevalence (adjusted OR (95% CI)xa0=xa01.28 (1.02-1.61), pxa0=xa00.03) of CAD, but not the extent of CAD (adjusted OR (95% CI)xa0=xa01.02 (0.86-1.2), pxa0=xa00.84).nnnCONCLUSIONnGender significantly affects vitamin D status. The lower 25(OH)D levels observed in females, as compared to males, play a more relevant role in conditioning the severity of CAD.

Meta-analysis of 14 trials comparing bypass grafting vs drug-eluting stents in diabetic patients with multivessel coronary artery disease

BACKGROUND AND AIMnClinical trials have reported lower mortality and repeated revascularization rate in diabetic patients treated with coronary artery bypass grafting (CABG) as compared to percutaneous revascularization. However, these studies were conducted in the era of bare-metal stents. Therefore, we performed a meta-analysis to compare CABG to PCI with drug-eluting stents (DES) in diabetic patients with multivessel and/or left main disease.nnnMETHODS AND RESULTSnThe literature was scanned by formal search of electronic databases (Medline, EMBASE, and Cochrane databases), and major international scientific session abstracts from 2000 to 2013. Primary endpoint was mortality. A total of 14 (4 randomized and 10 non-randomized) trials were finally included, with a total of 7072 patients. Up to 5 years follow-up, CABG was associated with a reduction in mortality (7.3% vs 10.4%, OR[95%CI]xa0=xa00.65[0.55-0.77], pxa0<xa00.0001; phetxa0=xa00.00001), with similar results in both RCTs (OR[95%CI]xa0=xa00.64[0.50-0.82], pxa0=xa00.0005) and NRCTs (OR[95%CI]xa0=xa00.75[0.6-0.94)], pxa0=xa00.01) (p intxa0=xa00.93). A significant relationship was observed between risk profile and benefits in mortality with CABG (pxa0<xa00.001). CABG reduced target vessel revascularization (TVR; 5.2% vs 15.7%, OR[95%CI]xa0=xa00.30[0.25-0.36], pxa0<xa00.00001, p hetxa0=xa00.02), with a relationship between risk profile and the benefits from CABG as compared to DES (pxa0<xa00.0001). CABG was associated with a lower rate of MACCE (14.9% vs 22.9%, OR[95%CI]xa0=xa00.59[0.51-0.67], pxa0<xa00.00001, p het<0.00001) but higher risk of CVA (3.6% vs 1.4%, OR[95%CI]xa0=xa02.34[1.63-3.35], pxa0<xa00.00001, p hetxa0=xa00.71).nnnCONCLUSIONSnThe present meta-analysis demonstrates that among diabetic patients with multivessel disease and/or left main disease, CABG provides benefits in mortality and TVR, especially in high-risk patients but it is counterbalanced by a higher risk of stroke. Future trials are certainly needed in the era of new DES and improved antiplatelet therapies.

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

BACKGROUNDnPeriprocedural 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.nnnMETHODSnWe 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.nnnRESULTSnWe 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).nnnCONCLUSIONSnThis study demonstrates that MPV does not predict the risk of PMI in patients undergoing PCI.

Platelet-large cell ratio and the extent of coronary artery disease: results from a large prospective study.

Even though platelet volume has been supposed to be indicator of platelet activation, contrasting results have been reported on its relationship with the extent of coronary artery disease (CAD). No data have been so far reported on Platelet-Large Cell Ratio (P-LCR). Thus, the aim of the current study was to investigate whether P-LCR is associated with CAD. We measured P-LCR in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between P-LCR and platelet aggregation was evaluated by PFA-100 and Multiplate. Patients with higher P-LCR were older (Pxa0=xa00.038), with larger prevalence of diabetes (Pxa0<xa00.0001), dilated cardiomyopathy or valvular heart disease (Pxa0=xa00.004) and less often family history of CAD (Pxa0=xa00.045), more often on statins (Pxa0=xa00.002), and diuretics (Pxa0=xa00.016). P-LCR was significantly associated with baseline glycaemia (Pxa0=xa00.001) and RBC count (Pxa0<xa00.001), but inversely related to platelet count (Pxa0<xa00.0001). P-LCR was not associated with the prevalence of CAD (adjusted Pxa0=xa00.3) or its severity. In addition, P-LCR was not related to Carotid IMT or platelet aggregation in patients with or without aspirin therapy. This study showed that P-LCR is not related to platelet aggregation, aspirin resistance, the extent of CAD and carotid IMT. Thus, P-LCR can not be considered as a marker of platelet reactivity or a risk factor for CAD.