Poor agreement between light transmission aggregometry, Verify Now P2Y12 and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials.

Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of "true poor responders" to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 µmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y12 (VN, results expressed as P2Y12 reaction unit: PRU) and vasodilatator-stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R(2 )= 0.642, p < 0.001), LTA/VASP (R(2 )= 0.409, p < 0.001) and VN/VASP (R(2 )= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as "poor or good responders" (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as "good" or "poor responders" by the three tests. Altogether, 33% of the patients were defined as "poor responders" by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as "poor or good responder" by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy.

Impact of initial clinical presentation on clopidogrel low response.

BACKGROUND: Large interindividual variability exists in clopidogrel response. Clopidogrel low response correlates with poor prognosis after percutaneous coronary intervention. Some authors also suggest intraindividual variability over time. AIM: To assess the impact of initial clinical presentation on clopidogrel low response. METHODS: In this prospective study, clopidogrel response was assessed in 100 patients. Fifty patients presenting with acute coronary syndromes (ACS group) were compared with 50 patients with stable coronary artery disease matched 1:1 for age, sex, body mass index and diabetes (stable group). All patients were tested 18-24h after a 600 mg loading dose of clopidogrel using the VerifyNow-P2Y12 test (results expressed as platelet reaction units [PRUs]). Patients under chronic clopidogrel therapy or treated with glycoprotein IIb/IIIa inhibitors, bivalirudin or thrombolytics were excluded. RESULTS: Mean age was 61 ± 12 years in each group; 28% of patients in each group were diabetic; mean body mass index was 27.6 ± 5.6 kg/m(2) in the ACS group and 27.9 ± 5.9 kg/m(2) in the stable group (p=0.80). Mean PRU values were 197 ± 81 in the ACS group and 159 ± 94 in the stable group (p=0.03). By multivariable analysis, the ACS group was significantly associated with a higher PRU value (p=0.02). There were significantly more clopidogrel low responders (PRU value>230) in the ACS group (38% vs. 18%; p=0.04). CONCLUSION: Our study confirms that initial clinical presentation, especially ACS, is a strong predictor of clopidogrel low response; this suggests that the evolution of coronary artery disease for one patient influences the clopidogrel response over time. These results are in accordance with recent trials showing a benefit for more aggressive antiplatelet therapy in ACS patients.

French Ministry of Health prospective multicentre study using bio-active stents coated with titanium nitride oxide: the EVIDENCE registry.

BACKGROUND: Coronary stents have evolved over time, from bare-metal stents to drug-eluting stents, and now to bioactive stents. AIMS: We sought to explore the immediate outcome of the titanium-nitride-oxide-coated bioactive stent, Titan2(®), in real-world practice, and the incidence of major cardiac events at follow-up. METHODS: Consecutive patients admitted for percutaneous intervention for at least one significant (≥50%) lesion in a native coronary artery were treated with Titan2(®) stent implantation. The primary endpoint was total major adverse cardiac events at 12-month follow-up. Secondary endpoints included target lesion revascularization at 12-month follow-up and the duration of dual antiplatelet therapy. RESULTS: Among 356 patients (mean age 67.4 ± 12.1 years), 77.2% were male and 39.3% were treated for myocardial infarction (MI). A total of 546 Titan2(®) stents were implanted in 420 lesions. Angiographic and clinical procedural success was achieved in all cases. No cases of in-hospital major adverse cardiac events or acute stent thrombosis were reported. Of 335 patients (94.1%) with 12-month clinical follow-up, four (1.2%) died, MI occurred in five (1.5%), target lesion revascularization was performed in 17 (5.1%) and major adverse cardiac events occurred in 24 (7.2%). One patient (0.3%) suffered late stent thrombosis during follow-up, but no cases of acute or subacute stent thrombosis occurred. Dual antiplatelet therapy continued beyond 6 months in 64.5% of patients. CONCLUSIONS: In real-world practice, Titan2(®) stent implantation achieves an excellent immediate outcome, with a low incidence of major adverse cardiac events at 12-month follow-up.

Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation: a review of the current guidelines and literature.

Dual antiplatelet therapy is the mainstay of medical treatment after percutaneous coronary intervention regarding the risk of stent thrombosis occurrence. Since the beginning of the stenting era, antiplatelet regimens have evolved according to the emerging and widespread diffusion of new devices and more challenging indications for their use. In the past years, concerns have been raised about the safety of drug-eluting stent implantation with regard to late and very late stent thrombosis. Thus, the length of dual antiplatelet therapy has been progressively increased with marked individual and local differences. However, prolonged antiplatelet therapy leads to increased risk of bleeding, especially in the setting of surgical procedures, traumas, and/or other diseases. To date, the exact duration of dual antiplatelet therapy after drug-eluting stent implantation is still debated in the literature. The aim of this article is to review the literature and the current guidelines on the risks and benefits of pursuing dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation.

Early and long-term results of unprotected left main coronary artery stenosis with paclitaxel-eluting stents: the FRIEND (French multicentre RegIstry for stenting of uNprotecteD LMCA stenosis) registry.

AIMS: To evaluate the angiographic and clinical outcome of patients undergoing paclitaxel-eluting stent (PES) implantation for unprotected left main coronary artery (ULMCA) stenosis in a "real-world" multicentre, prospective registry. Percutaneous coronary intervention (PCI) is an increasingly utilised method of revascularisation in patients with ULMCA. METHODS AND RESULTS: A prospective registry including all patients with a significant (>50%) ULMCA stenosis. Of 151 such patients, the target lesion involved the distal bifurcation in 100 patients (66%), which was treated predominantly by a "provisional T-stenting" strategy. In the distal ULMCA disease group, 72% had only one stent implantation while 28% had multiple (either two or three) stents implanted. At a median follow-up of 1,123±80 days, cardiac death occurred in five patients (3.3%) and major adverse cardiac and cerebrovascular events (MACCE) in 32 patients (21.2%). The three-year survival rate was 93.3%. CONCLUSIONS: In the drug-eluting stent era, paclitaxel-eluting stent implantation of ULMCA stenosis provided excellent immediate and long-term results in this selected population, suggesting that this approach may be considered as a safe and effective alternative to CABG for selected patients with ULMCA who are treated in experienced institutions performing large numbers of PCI procedures.

Hybrid revascularization, comprising coronary artery bypass graft with exclusive arterial conduits followed by early drug-eluting stent implantation, in multivessel coronary artery disease.

AIM: To assess the feasibility and safety of a hybrid myocardial revascularization strategy combining "exclusive arterial" conventional coronary artery bypass grafting (CABG) followed by early drug-eluting stent (DES) implantation in multivessel coronary artery disease (CAD). METHODS: Eighteen consecutive patients with multivessel CAD were enrolled prospectively. Within 48 hours of CABG using left internal mammary artery (IMA) to left anterior descending (LAD) coronary artery with or without right IMA to non-LAD vessel in an open chest approach, DESs were implanted systematically in an additional vessel after a clopidogrel 300-mg preloading dose. This group was compared with 18 matched patients who underwent standard CABG alone using left IMA to LAD and at least one additional graft. RESULTS: Baseline clinical characteristics were similar in both groups. There were 46 grafts in the CABG group and 28 in the hybrid group. In the hybrid group, 27.8% of patients were treated off-pump versus none in the CABG group; a median of 2 (interquartile range: 1-2) stents was implanted per patient. The hybrid procedure was associated with shorter durations of cardiopulmonary bypass (77 [67-100] min versus 97 [90-105] min, P=0.049). Major bleeding rates were higher in the CABG group, but the difference was not statistically significant (44.4% versus 11.1%, P=0.06). Re-intervention for bleeding was not needed in either group. One (5.6%) myocardial infarction occurred in hospital in each group following CABG. At 1 year, the cumulative rates of major adverse cardiac events (death, myocardial infarction, target vessel revascularization) were similar (11.2% in hybrid group versus 5.6% in CABG group, P=0.99). One death occurred in the CABG group and one target vessel revascularization in the hybrid group. CONCLUSION: A hybrid revascularization strategy, combining conventional CABG with exclusive arterial conduits followed by early DES implantation, is feasible. One-year event rates compare favourably to those with traditional CABG alone.

Randomized comparison of eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI Trial.

OBJECTIVES: The aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI). BACKGROUND: The glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI. METHODS: A total of 427 patients with ST-segment elevation myocardial infarctions <12 h and planned primary PCI were randomized to double-bolus eptifibatide (n = 226) followed by a 24-h infusion or single-bolus abciximab (n = 201) followed by a 12-h infusion. In this noninferiority trial, the primary end point was the incidence of complete (> or =70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial reperfusion. The assumption was a 60% complete STR rate in the abciximab group. The noninferiority margin was set to 15%. RESULTS: The incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after eptifibatide and abciximab, respectively. CONCLUSIONS: Eptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751).

Impact of thrombus aspiration use and direct stenting on final myocardial blush score in patients presenting with ST-elevation myocardial infarction.

BACKGROUND: Many studies have reported that low final thrombolysis in myocardial infarction (TIMI) flow and/or myocardial blush grade (MBG) are independent predictors of mortality in patients with ST-elevation myocardial infarction (STEMI). In addition, distal coronary embolization is a major pitfall of conventional percutaneous coronary intervention (PCI) in such a context. AIM: This study aimed to assess the impact of thrombus aspiration (TA) use before primary PCI on final myocardial reperfusion in patients presenting with STEMI. METHODS: From January to December 2006, 100 patients presenting with STEMI in our catheterization laboratory were considered for the present study. During this time period, 50 patients underwent TA before primary PCI for treatment of STEMI and were then matched 1:1 to 50 controls who underwent conventional primary PCI for treatment of STEMI without TA. Patients of the control group were chosen after matching on age+/-3 years, sex, history of diabetes, and distribution of the infarct related coronary artery during the same period. RESULTS: Baseline clinical characteristics, initial TIMI flow and initial MBG of both groups were similar. There was a trend for a better final TIMI flow in the group with TA and the final MBG was significantly improved in the group with TA compared to the group without TA: final MBG of two or three in 70% versus 30% of the cases (P=.001). In addition, direct stenting was significantly more often used in the TA group (92% versus 64%, P=.001). There were four patients with evident distal embolizations in the group without TA and none in the group with TA. CONCLUSION: TA use before primary PCI for STEMI treatment resulted in improved final myocardial reperfusion. Of importance, TA use may have led to a better choice of the stent size and more frequent direct stenting. This benefit may directly improve patient outcomes.

Dosing strategies for antiplatelet therapy in percutaneous coronary intervention.

Both clopidogrel and aspirin have been shown to decrease the rate of cardiovascular events and especially stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, recent studies have suggested that there is large inter-individual response variability to these drugs (especially to clopidogrel) and that improved inhibition of platelet reactivity using higher doses or new, more potent agents would further reduce the occurrence of cardiovascular events, but may also increase the risk of bleeding. Many different protocols of antiplatelet therapy have been studied and have shown benefit in reducing the rate of major adverse cardiovascular events after PCI. Therefore, the choice of an appropriate antiplatelet therapy protocol is sometimes difficult for the clinician and should be individualized as per the particular patient risk, accounting for both the risk of recurrent cardiovascular events and bleeding. We review the recent data on efficacy and safety of dosing strategies for antiplatelet therapy in PCI.

Comparison of the efficacy of rosuvastatin versus atorvastatin in reducing apolipoprotein B/apolipoprotein A-1 ratio in patients with acute coronary syndrome: results of the CENTAURUS study.

BACKGROUND: The mechanism underlying statin-induced event reduction in patients with acute coronary syndrome remains unclear. AIMS: To assess the efficacy of rosuvastatin 20mg versus atorvastatin 80 mg in reducing the apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio at 3 months. Non-inferiority of rosuvastatin 20mg versus atorvastatin 80 mg in reducing low-density lipoprotein cholesterol at 1 and 3 months was also assessed. METHODS: Patients with non-ST-elevation acute coronary syndrome were enrolled into this randomized, double blind, parallel-group trial. RESULTS: In total, 753 patients (369, rosuvastatin 20mg; 384, atorvastatin 80 mg) were included in the intention-to-treat analysis; 478 patients (226, rosuvastatin 20mg; 252, atorvastatin 80 mg) were included in the per-protocol analysis. Rosuvastatin 20mg was more effective than atorvastatin 80 mg in decreasing apoB/apoA-1 ratio at 1 month (-44.4% vs -42.9%, p=0.02) but not at 3 months (both -44.4%, p=0.87). Low-density lipoprotein cholesterol decreased by approximately 50% after 1 and 3 months in both groups. Non-inferiority of rosuvastatin 20mg versus atorvastatin 80 mg was demonstrated at 1 month (difference, -0.3% [95% confidence interval, -2.7; +2.1]), but not at 3 months (+1.0% [-1.6; 3.5]) (intention-to-treat analysis). In the per-protocol analysis, non-inferiority of rosuvastatin 20mg was demonstrated at both 1 (-0.7% [-3.5; 2.0]) and 3 (-0.5% [-3.5; 2.5]) months. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome, rosuvastatin 20mg decreased apoB/apoA-1 ratio at 1 month more than atorvastatin 80 mg. No difference could be shown at 3 months; thus, the primary endpoint was not met.

Thrombus aspiration for the treatment of definite stent thrombosis.

BACKGROUND: Thrombus aspiration (TA) has been associated with high rates of thrombotic material retrieval, which results in improved myocardial reperfusion. In addition, a recent study has shown that systematic TA for treatment of ST-segment elevation myocardial infarction (STEMI) related to de novo lesions improves patient outcomes. AIMS: Evaluation of a single-centre experience of TA before percutaneous coronary intervention (PCI) for stent thrombosis (ST) treatment. METHODS: Between 2004 and 2006, we indexed 24 patients presenting with definite ST. All patients underwent TA (Export Medtronic 6F catheter) followed by PCI for ST treatment. Baseline clinical and angiographic characteristics, and complications related to the TA device were indexed. RESULTS: The median time of ST occurrence was 7 days. All patients except one presented with STEMI. Bare-metal and drug-eluting ST represented 70.8% and 29.2% of cases, respectively. Mean stent length was 18.8 + or - 5.6mm; mean stent diameter was 2.8 + or - 0.4mm; mean number of implanted stents was 1.58 + or - 0.7. There was no failure to cross the catheter and no TA device-related complications were reported. The numbers of patients with initial thrombolysis in myocardial infarction (TIMI) flow grades 0, 1 and 2 were 15 (62.5%), 3 (12.5%) and 6 (25.0%), respectively. No patient had TIMI flow grade 3 before TA. After TA, 16 (66.7%) patients had TIMI flow grade 3; final procedural success was obtained in 23 (95.8%) patients. The 1-year death rate was 12.5%. CONCLUSIONS: In our experience, TA before PCI for ST treatment shows promising results, providing high rates of immediate reperfusion and final angiographic success, and low death rates, compared with the literature.

Preprocedural high-sensitivity C-reactive protein predicts death or myocardial infarction but not target vessel revascularization or stent thrombosis after percutaneous coronary intervention.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) elevation is associated with poor clinical outcome in patients with coronary artery disease (CAD). However, the prognostic value of preprocedural hs-CRP elevation before coronary stent implantation remains debated especially regarding restenosis and target vessel revascularization (TVR). Furthermore, whether hs-CRP elevation may predict stent thrombosis (ST) is unknown. METHODS: We included 560 consecutive patients, who underwent coronary stent implantation in our institution. Blood samples for hs-CRP determination were obtained immediately before the procedure. During a median follow-up of 12.5 months, cardiovascular events including death, myocardial infarction (MI), TVR, and ST were systematically included. RESULTS: Median hs-CRP was 3.10 [25-75th percentile: 1.36-8.63] mg/l. There were 27 (4.8%) deaths, 17 (3.1%) nonfatal MI, 58 (10.5%) TVR, and 12 (2.1%) ST. The composite criteria death-MI occurred in 44 (7.9%) patients. Independent predictors of the composite death-MI were hs-CRP level [hazard ratio (HR)=1.33 (95% CI: 1.05-1.70); P=.021], diabetes (P=.003), and multivessel CAD (P=.011). The composite death-MI occurred in 31 (13.3%) of the 233 patients with hs-CRP >4.63 mg/l vs. 13 (4.0%) of the 327 patients with hs-CRP <4.63 mg/L (P<.001). By contrast, hs-CRP predicted neither TVR [HR=0.88 (0.73-1.08); P=.23] nor ST [HR=1.15 (0.77-1.71); P=.49]. CONCLUSION: High hs-CRP levels before coronary stent implantation are associated with risk of death or MI, but are not related to TVR or ST. These data suggest that preprocedural hs-CRP is more a predictor of global cardiovascular risk than a predictor of stent-related complications.

The development of an international, common, prospective, cardiology database. Report of the joint G8 Cardio-Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO)--Societé Française de Cardiologie (SFC) database committee.

BACKGROUND: Sharing and comparing health data at the international level is made difficult by heterogeneity in real world databases. AIM: Our primary objective was to field-test the implementation of the first common database developed conjointly by different national cardiological societies. METHODS: Based upon G8-Cardio feasibility projects, the Italian Society of Hospital Cardiologists and the French Society of Cardiology joined together to standardize a cardiological, patient-oriented database, created by means of consensus agreement for sharing data in a common server. Quantification of standardization was obtained by analysing each dataset according to the possibility of merging corresponding fields. Data merging from national centres was completed in the common server and after proper data integration in the common database; a comparison was performed between French and Italian populations. RESULTS: Standardization of contents allowed for 89% overall interoperability (merged fields) to be achieved with only 11% divergent fields. All (100%) merged homogeneous data on the first 2717 patients from peripheral centres were selected consecutively from the common database and analysed successfully. Relevant differences between the two populations were outlined. CONCLUSIONS: The international standardization and sharing/merging of databases is feasible. This model opens the way to important applications in internationally shared health care policies.

Impact of high loading and maintenance dose of clopidogrel within the first 15 days after percutaneous coronary intervention on patient outcome.

BACKGROUND: An increase in clopidogrel dose results in an improved inhibition of platelet aggregation. However, whether an increase in clopidogrel dose may improve patient outcome is still debated. The aim of this study was to analyze the impact on patient outcome of an increase in clopidogrel loading and maintenance doses within the first 15 days after percutaneous coronary intervention (PCI). METHODS: Between 2003 and 2007, we included 2,954 consecutive patients who underwent PCI and stent implantation. We compared 2 historical groups. In the "low-dose" group (2003-2005, n = 1,984), patients were pretreated with a 300-mg clopidogrel loading dose followed by 75 mg/d after PCI. In the "high-dose" group (2006-2007, n = 970), patients were pretreated with a 600-mg clopidogrel loading dose followed by 150 mg/d within the first 15 days and 75 mg/d thereafter. The composite primary end point (death, myocardial infarction, stent thrombosis) and bleeding were systematically indexed during the 2-month follow-up period. RESULTS: Clinical and most of angiographic characteristics were similar between the 2 groups. By multivariate analysis, high dose of clopidogrel was associated with a decrease in the composite primary end point (hazard ratio 0.694, 95% CI 0.485-0.993, P = .046). The other predictors were age, left ventricular ejection fraction, diabetes, renal failure, and acute coronary syndrome. Major bleeding was similar in the low- and high-dose groups (2.8% vs 3.4%, respectively, P = .379). After propensity score matching, the high-dose group was still associated with a significant clinical benefit. CONCLUSION: Our results show that a 600-mg loading dose followed by a 150-mg maintenance dose of clopidogrel within the first 15 days after PCI is independently associated with a decrease in the composite death-myocardial infarction-stent thrombosis at 2 months without increase in hemorrhagic complications.

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient.

Despite current standards of care aimed at achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure and glycaemia, dyslipidaemic patients remain at high residual risk of vascular events. Atherogenic dyslipidaemia, specifically elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease, type 2 diabetes, obesity or metabolic syndrome and is associated with macrovascular and microvascular residual risk. The Residual Risk Reduction Initiative (R3I) was established to address this important issue. This position paper aims to highlight evidence that atherogenic dyslipidaemia contributes to residual macrovascular risk and microvascular complications despite current standards of care for dyslipidaemia and diabetes, and to recommend therapeutic intervention for reducing this, supported by evidence and expert consensus. Lifestyle modification is an important first step. Additionally, pharmacotherapy is often required. Adding niacin, a fibrate or omega-3 fatty acids to statin therapy improves achievement of all lipid risk factors. Outcomes studies are evaluating whether these strategies translate to greater clinical benefit than statin therapy alone. In conclusion, the R3I highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual vascular risk among dyslipidaemic patients who are treated in accordance with current standards of care.

High incidence of recurrent in stent thrombosis after successful treatment of a first in stent thrombosis.

OBJECTIVES: We attempted to investigate incidence and predictors of recurrent in stent thrombosis (IST) after successful treatment of a first IST. BACKGROUND: The occurrence of recurrent IST after successful treatment of a first IST may be a decisive factor for patient clinical outcome. However, incidence and predictors of recurrent IST are currently poorly described in the literature. METHODS: Between 2003 and 2005, 2,190 patients underwent a percutaneous coronary intervention in our center. During a median follow-up of 19.4 months, 49 patients (2.24%) presented a first definite IST. Patients presenting with a first IST were followed during an additional median period of 40 months. Their baseline characteristics were listed and cardiovascular events especially recurrent IST as defined by the Academic Research Consortium definition were systematically indexed. RESULTS: Altogether 39 (80%) patients were successfully treated with an effective reperfusion after percutaneous coronary intervention. Fourteen (36%) patients presented a recurrent IST and three presented multiple recurrent IST. The median occurrence time of recurrent IST was 5 days, range between 1 and 11 days. Multivariate analysis identified history of neoplasia (HR = 11.53, 95% CI 2.32-57.37, P = 0.003), residual diameter stenosis (HR = 1.15, 95% CI 1.02-1.29, P = 0.02), and residual dissection after treatment (HR = 8.78, 95% CI 1.85-41.62, P = 0.006), as independent predictors of recurrent IST. CONCLUSION: Recurrent IST is a frequent and early event after successful treatment of a first IST. Our results suggest that mechanical factors like residual dissection and residual diameter stenosis should be carefully tracked down. In addition, patients with multiple recurrent IST and the early time course of recurrent IST also suggest a potential role of inadequate antiplatelet therapy.

Effects of rosuvastatin and atorvastatin on the apolipoprotein B/apolipoprotein A-1 ratio in patients with an acute coronary syndrome: The CENTAURUS trial design.

BACKGROUND: The mechanism underlying rapid, statin-induced event reduction in patients with an acute coronary syndrome (ACS) remains to be clarified. AIM: The primary objective is to compare the efficacy of rosuvastatin 20 mg/day and atorvastatin 80 mg/day in reducing the apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio at three months, in ACS patients. Secondary objectives include a comparison of the effects of early-started rosuvastatin and placebo on inflammatory markers. METHODS: This is a randomized, double-blind, parallel-group study. Patients with non-ST-segment elevation ACS, symptom onset less than 48 h before admission, and for whom a percutaneous coronary intervention is planned, are eligible for inclusion and are randomized into three groups (G1, G2 and G3). The study comprises two double-blind periods. Period 1 starts at hospital admission and lasts until Day 0 (discharge or less or equal to 6 days after admission); patients in G1 receive one tablet of rosuvastatin 20 mg/day and patients in G2 and G3 receive one matching placebo tablet per day. Period 2 starts at Day 0 and lasts for three months; patients in G1 continue to receive rosuvastatin 20 mg/day, patients in G2 receive rosuvastatin 20 mg/day and patients in G3 receive atorvastatin 80 mg/day. Recruitment of 1075 patients will ensure an 80 power to detect a 3% difference in percentage change in the apoB/apoA-1 ratio and a 20% difference in percentage change in high-sensitivity C-reactive protein. RESULTS: Inclusion phase is complete; results will be reported at a later date. CONCLUSION: This is the first trial investigating the effect of statins on apolipoproteins in ACS patients.