Treatment Characteristics and Real-World Progression-Free Survival in Patients With Unresectable Stage III NSCLC Who Received Durvalumab After Chemoradiotherapy: Findings From the PACIFIC-R Study.

INTRODUCTION: The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS). METHODS: PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan-Meier method). RESULTS: As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1-24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease. CONCLUSIONS: Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.

Circulating free tumor-derived DNA to detect EGFR mutations in patients with advanced NSCLC: French subset analysis of the ASSESS study.

BACKGROUND: The non-interventional ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for epidermal growth factor receptor (EGFR) mutation testing in patients with advanced non-small-cell lung cancer (NSCLC), in a real-world setting across 56 centers in Europe and Japan. The high mutation status concordance between 1162 matched tissue/cytology and plasma samples (89%, sensitivity =46%, specificity =97%) suggested that ctDNA is a feasible sample for EGFR mutation analysis. We report data for the French subset of patients (pre-planned analysis). METHODS: Eligible patients (stage IIIA/B/IV locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytology and plasma samples. DNA extracted from tissue/cytology samples was subjected to EGFR mutation testing as per local practice; a designated laboratory performed ctDNA extraction/mutation testing of plasma samples. The primary outcome was EGFR mutation status concordance between matched tumor and plasma samples. RESULTS: Of the 1,311 patients enrolled in the ASSESS trial, 145 were recruited from 9 centers in France. Tumor samples from 130 patients were collected and 126 were evaluable for EGFR mutation analysis. Activating EGFR mutations were identified in 13 of the 126 patient tumor samples (EGFR mutation frequency 10.3%). For plasma testing, 10 of the 145 samples tested were positive for EGFR mutations (EGFR mutation frequency 6.9%). EGFR mutation rate was significantly higher in never- versus ever-smokers (stepwise logistic regression: tumor, P<0.0001; plasma, P=0.0008). Mutation status concordance between 126 matched patient samples was 96.0% [121/126; 95% confidence intervals (CI), 91.0-98.7]. Of the 113 EGFR mutation-negative patient tissue samples, one tested plasma-positive; reanalysis of plasma via two different techniques confirmed the presence of a L858R mutation, indicating a tissue false-negative result. Based on these data, sensitivity of plasma testing was 64.3% (9/14; 95% CI, 35.1-87.2%) and its specificity was 100.0% (112/112; 95% CI, 96.8-100.0%). CONCLUSIONS: Data confirm ctDNA as an alternative sample for EGFR mutation analysis in patients with advanced NSCLC.

Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine.

BACKGROUND: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management. METHODS: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded. RESULTS: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02). CONCLUSIONS: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Association Between Clinical Pathways Leading to Medical Management and Prognosis in Patients With NSTEACS.

INTRODUCTION AND OBJECTIVES: A large proportion of patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) are initially selected for medical management (MM) and do not undergo coronary revascularization during or immediately after the index event. The aim of this study was to explore the clinical pathways leading to MM in NSTEACS patients and their influence on prognosis. METHODS: Patient characteristics, pathways leading to MM, and 2-year outcomes were recorded in a prospective cohort of 5591 NSTEACS patients enrolled in 555 hospitals in 20 countries across Europe and Latin America. Cox models were used to assess the impact of hospital management on postdischarge mortality. RESULTS: Medical management was the selected strategy in 2306 (41.2%) patients, of whom 669 (29%) had significant coronary artery disease (CAD), 451 (19.6%) had nonsignificant disease, and 1186 (51.4%) did not undergo coronary angiography. Medically managed patients were older and had higher risk features than revascularized patients. Two-year mortality was higher in medically managed patients than in revascularized patients (11.0% vs 4.4%; P < .001), with higher mortality rates in patients who did not undergo angiography (14.6%) and in those with significant CAD (9.3%). Risk-adjusted mortality was highest for patients who did not undergo angiography (HR = 1.81; 95%CI, 1.23-2.65), or were not revascularized in the presence of significant CAD (HR = 1.90; 95%CI, 1.23-2.95) compared with revascularized patients. CONCLUSIONS: Medically managed NSTEACS patients represent a heterogeneous population with distinct risk profiles and outcomes. These differences should be considered when designing future studies in this population.

Prehospital and in-hospital use of healthcare resources in patients surviving acute coronary syndromes: an analysis of the EPICOR registry.

OBJECTIVE: The aim of this report is to provide insight into real-world healthcare resource use (HCRU) during the critical management of patients surviving acute coronary syndromes (ACS), using data from EPICOR (long-tErm follow-up of antithrombotic management Patterns In acute CORonary syndrome patients) (NCT01171404). METHODS: EPICOR was a prospective, multinational, observational study that enrolled 10 568 ACS survivors from 555 hospitals in 20 countries in Europe and Latin America, between September 2010 and March 2011. HCRU was evaluated in patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS), with or without a history of cardiovascular disease (CVD). Multivariable analysis was performed to determine factors that affected resource use. RESULTS: Before hospitalisation, more patients with STEMI than with NSTE-ACS had their first ECG (44.1% vs 36.4%, p<0.0001) and received antithrombotic medication (26.6% vs 15.2%, p<0.0001). Patients with NSTE-ACS with prior CVD were less likely than those without to be catheterised (73.1% vs 82.8%, p<0.0001). More patients with STEMI than with NSTE-ACS had percutaneous coronary intervention (77.1% vs 54.9%, p<0.0001), but fewer underwent coronary artery bypass grafting (1.2% vs 3.7%, p<0.0001). Multivariable analysis showed that resource use, including length of hospital stay and coronary revascularisation, was significantly influenced by multiple factors, including ACS type, site characteristics and region (all p≤0.05). CONCLUSIONS: In this large-scale, real-life study, findings were generally in line with clinical logic, although site characteristics and region still significantly affected resource use. Moreover, and unexpectedly, resource use tended to be slightly higher in patients without a history of CVD. TRIAL REGISTRATION NUMBER: NCT01171404 (ClinicalTrials.gov).

Effect of Pre-Hospital Ticagrelor During the First 24 h After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H²4 Analysis.

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study. BACKGROUND: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. RESULTS: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).

Opportunities for improvement in anti-thrombotic therapy and other strategies for the management of acute coronary syndromes: Insights from EPICOR, an international study of current practice patterns.

AIMS: To describe international patterns and opportunities for improvement of pre- and in-hospital care of patients hospitalized for acute coronary syndromes (ACS), with special focus on anti-thrombotic therapy. METHODS AND RESULTS: EPICOR (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary syndrome patients), an international, cohort study, which enrolled 10,568 consecutive ACS survivors from 555 hospitals in 20 countries across Europe and Latin America (September 2010 to March 2011), prospectively registered detailed information on pre- and in-hospital management. Globally, 4738 (44.8%) were attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944 patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel, single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of ACS patients were medically managed. A significant decreasing gradient was found between Northern, Southern and Eastern Europe and Latin America in use of more potent patterns of anti-platelet therapy, reperfusion therapy and invasive strategy. CONCLUSION: This large international study shows room for improvement in use of anti-thrombotic drugs and other strategies for optimal management of ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice differences not based on evidence or conditioned by economic constraints should be reduced.

Predictors of one-year mortality at hospital discharge after acute coronary syndromes: A new risk score from the EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients) study.

AIMS: A reliable prediction tool is needed to identify acute coronary syndrome (ACS) patients with high mortality risk after their initial hospitalization. METHODS: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients: NCT01171404) is a prospective cohort study of 10,568 consecutive hospital survivors after an ACS event (4943 ST-segment elevation myocardial infarction (STEMI) and 5625 non-ST-elevation ACS (NSTE-ACS)). Of these cases, 65.1% underwent percutaneous coronary intervention (PCI) and 2.5% coronary artery bypass graft (CABG). Post-discharge mortality was recorded for up to two years. From over 50 potential predictor variables a new risk score for one-year mortality was developed using forward stepwise Cox regression, and examined for goodness-of-fit, discriminatory power, and external validation. RESULTS: A total of 407 patients (3.9%) died within one year of discharge. We identified 12 highly significant independent predictors of mortality (in order of predictive strength): age, lower ejection fraction, poorer EQ-5D quality of life, elevated serum creatinine, in-hospital cardiac complications, chronic obstructive pulmonary disease, elevated blood glucose, male gender, no PCI/CABG after NSTE-ACS, low hemoglobin, peripheral artery disease, on diuretics at discharge. When combined into a new risk score excellent discrimination was achieved (c-statistic=0.81) and this was also validated on a large similar cohort (9907 patients) in Asia (c=0.78). For both STEMI and NSTE-ACS there was a steep gradient in one-year mortality ranging from 0.5% in the lowest quintile to 18.2% in the highest decile. NSTE-ACS contributes over twice as many high-risk patients as STEMI. CONCLUSIONS: Post-discharge mortality for ACS patients remains of concern. Our new user-friendly risk score available on www.acsrisk.org can readily identify who is at high risk.

Contemporary inter-hospital transfer patterns for the management of acute coronary syndrome patients: findings from the EPICOR study.

AIM: The EPICOR observational study was designed to describe antithrombotic strategies in a broad acute coronary syndrome (ACS) population; it also included information on inter-hospital transfers and institutional resources. METHODS AND RESULTS: EPICOR enrolled 10,568 consecutively discharged patients with ST-elevation (STE) or non-STE (NSTE) ACS in 555 centres in 20 countries across Europe and Latin America. Patients were categorized as non-transferred, transferred in from another hospital and then discharged, or transferred out to a second hospital but discharged from their initial hospital after transfer back. Two-thirds of ACS patients were non-transferred, of which only 14% were hospitalized at a centre without a catheterization laboratory, and one-third were transferred in or transferred out. Almost all transferred out patients were transferred out to a hospital with catheterization facilities, most often for primary/urgent/rescue (78%) or planned catheterization (18%) in STE myocardial infarction (STEMI), and primary/urgent/rescue (44%) or planned (43%) catheterization in NSTE-ACS. Transferred in patients were more likely to have a STEMI (60%) than non-transferred (44%) and transferred out patients (36%). In STEMI patients, time from symptom onset to catheterization was shorter in non-transferred patients (median 3.5 h vs. 5.9 h for transferred in and 6.3 h for transferred out). In NSTE-ACS, cardiac markers were positive in 66% of non-transferred patients versus 78% and 82% in transferred in and transferred out, respectively. CONCLUSIONS: The lack of on-site 24/7 facilities or the availability of more advanced care are frequent reasons for inter-hospital transfer in ACS. Further follow-up of these patients will help to determine whether these practice patterns affect outcome.

Prehospital ticagrelor in ST-segment elevation myocardial infarction.

BACKGROUND: The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. METHODS: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. RESULTS: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used. CONCLUSIONS: Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.).

Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study.

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.

Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial.

BACKGROUND: No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. METHODS: In this randomised, double-blind, phase 2 trial, we enrolled adults (aged ≥18 years) with locally advanced or metastatic differentiated thyroid carcinoma (papillary, follicular, or poorly differentiated) at 16 European medical centres. Eligible patients were sequentially randomised in a 1:1 ratio with a standard computerised scheme to receive either vandetanib 300 mg per day (vandetanib group) or matched placebo (placebo group), balanced by centre. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population based on investigator assessment. This study is registered with ClinicalTrials.gov, number NCT00537095. FINDINGS: Between Sept 28, 2007, and Oct 16, 2008, we randomly allocated 72 patients to the vandetanib group and 73 patients to the placebo group. By data cutoff (Dec 2, 2009), 113 (78%) patients had progressed (52 [72%] patients in the vandetanib group and 61 [84%] in the placebo group) and 40 (28%) had died (19 [26%] patients in the vandetanib group and 21 [29%] in the placebo group). Patients who received vandetanib had longer PFS than did those who received placebo (hazard ratio [HR] 0·63, 60% CI 0·54-0·74; one-sided p=0·008): median PFS was 11·1 months (95% CI 7·7-14·0) for patients in the vandetanib group and 5·9 months (4·0-8·9) for patients in the placebo group. The most common grade 3 or worse adverse events were QTc prolongation (ten [14%] of 73 patients in the vandetanib group vs none in the placebo group), diarrhoea (seven [10%] vs none), asthenia (five [7%] vs three [4%]), and fatigue (four [5%] vs none). Two patients in the vandetanib group and one in the placebo group died from treatment-related serious adverse events (haemorrhage from skin metastases and pneumonia in the vandetanib group and pneumonia in the placebo group). INTERPRETATION: Vandetanib is the first targeted drug to show evidence of efficacy in a randomised phase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma. Further investigation of tyrosine-kinase inhibitors in this setting is warranted. FUNDING: AstraZeneca.

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.

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.