Triple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine.

Statins, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs) have markedly changed the clinical progression of patients with coronary artery disease (CAD). The goal of this paper is to review the rationale and evidence for combining these three drug classes in hypertensive patients with hypercholesterolemia or CAD. Data sources include a literature search for publications on the use of a statin combined with various antihypertensive drugs in patients with hypertension and hypercholesterolemia or stable CAD. Hypercholesterolemia and hypertension constitute major physiological risk factors of ischemic heart disease. Current guidelines recommend a global approach to risk management, using agents that address as many risk factors as possible. Dual combination therapies are an important component of guideline-recommended therapy in hypertension. Our review of the literature indicates that triple therapy with a statin, ACE inhibitor, and CCB is associated with a significant reduction in major cardiovascular events. For example, a post hoc analysis in 1056 patients with stable CAD participating in the EUROPA trial indicated that the addition of perindopril to a CCB and a lipid-lowering agent was associated with a 46 % reduction in the composite of cardiovascular death, myocardial infarction, and resuscitated cardiac arrest (p = 0.023). In addition, single pill formulations are known to result in better adherence to the treatment. Single-pill formulations that combine a statin, an ACE inhibitor, and a CCB appear to offer an effective approach to the management of global cardiovascular risk.

Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model.

BACKGROUND: Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. METHODS AND RESULTS: Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective. CONCLUSIONS: Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit.

Impact of anticoagulation regimen prior to revascularization in patients with non-ST-segment elevation acute coronary syndromes: The ACUITY trial.

AIM: To evaluate the impact of antithrombotic regimens during the medical phase of treatment among 13,819 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) treated with an early invasive strategy in the acute catheterization and urgent intervention triage strategy (ACUITY) trial. METHODS AND RESULTS: Endpoints included composite major adverse cardiac events (MACE), major bleeding, and net adverse clinical events (NACE; MACE or major bleeding). The median (interquartile range) duration of antithrombin use in the medical only treatment phase was 6.5 (1.8-22.5) hours. MACE, major bleeding, and NACE during the medical only phase occurred in 63 (0.5%), 117 (0.9%), and 178 (1.3%) patients, respectively. MACE rates in the medical-treatment-only phase were not significantly different between the four randomized medical regimens used (heparin alone, bivalirudin alone, heparin plus a glycoprotein IIb/IIIa inhibitor [GPI], and bivalirudin plus GPI) (Ptrend = 0.65). The lowest rates of major bleeding and NACE during the medical treatment phase occurred in patients treated with bivalirudin alone (Ptrend = 0.0006 and Ptrend = 0.0004, respectively). CONCLUSIONS: In patients with NSTE-ACS undergoing an early invasive strategy, treatment with bivalirudin alone significantly reduced major bleeding and improved net clinical outcomes during the upstream medical management phase with comparable rates of MACE. © 2015 Wiley Periodicals, Inc.

Perindopril and ß-blocker for the prevention of cardiac events and mortality in stable coronary artery disease patients: A EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) subanalysis.

BACKGROUND: ß-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to ß-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including ß-blocker. METHODS: EUROPA was a multicenter, double-blind, placebo-controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received ß-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. RESULTS: At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received ß-blocker. Treatment with perindopril/ß-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/ß-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/ß-blocker. CONCLUSIONS: The addition of perindopril to ß-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including ß-blocker.

Incidence and impact of totally occluded culprit coronary arteries in patients presenting with non-ST-segment elevation myocardial infarction.

The accuracy of the 12-lead electrocardiogram in detecting coronary artery occlusion is limited. We sought to determine the incidence, distribution, and outcomes of patients who have total occlusion of the culprit artery but present with non-ST-segment elevation myocardial infarction (NSTEMI). The randomized Acute Catheterization and Urgent Intervention Triage Strategy trial enrolled 13,819 patients presenting with non-ST-segment elevation acute coronary syndromes who underwent an early invasive strategy. The present study includes 1,319 patients with baseline biomarker elevation (NSTEMI) and no history of coronary artery bypass graft who underwent percutaneous coronary intervention of a single culprit vessel. We compared the baseline characteristics and outcomes according to whether the culprit vessel was occluded (baseline Thrombolysis In Myocardial Infarction [TIMI] 0 to 1) or patent (TIMI 2 to 3 flow) by angiographic core laboratory assessment. TIMI 0 to 1 flow in the culprit artery was present in 262 of 1,319 (19.9%) patients. The incidence of coronary occlusion was 28.4%, 19.3%, and 12.6% in patients with NSTEMI because of right coronary, left circumflex, and left anterior descending artery disease, respectively. Patients with an occluded culprit artery were more commonly men and had ST-segment deviation ≥1 mm. One-year outcomes, including death (3.5% vs 3.0%, p = 0.68) and myocardial infarction (8.4% vs 9.6%, p = 0.47), did not differ significantly between patients with versus without occluded culprit arteries, respectively. In conclusion, the present study demonstrates that the culprit artery is totally occluded in approximately 1 in 5 patients presenting with NSTEMI and single-vessel disease; however, the presence of total occlusion in NSTEMI was not associated with an incremental hazard of death or reinfarction at 1 year.

Prognostic value of angiographic lesion complexity in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the acute catheterization and urgent intervention triage strategy trial).

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

Impact of nonculprit vessel myocardial perfusion on outcomes of patients undergoing percutaneous coronary intervention for acute coronary syndromes: analysis from the ACUITY trial (Acute Catheterization and Urgent Intervention Triage Strategy).

OBJECTIVES: This study evaluated the impact of nonculprit vessel myocardial perfusion on outcomes of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients. BACKGROUND: ST-segment elevation myocardial infarction patients have decreased perfusion in areas remote from the infarct-related vessel. The impact of myocardial hypoperfusion of regions supplied by nonculprit vessels in NSTE-ACS patients treated with percutaneous coronary intervention (PCI) is unknown. METHODS: The angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial included 6,921 NSTE-ACS patients. Complete 3-vessel assessments of baseline coronary TIMI (Thrombolysis In Myocardial Infarction) flow grade and myocardial blush grade (MBG) were performed. We examined the outcomes of PCI-treated patients according to the worst nonculprit vessel MBG identified per patient. RESULTS: Among the 3,826 patients treated with PCI, the worst nonculprit MBG was determined in 3,426 (89.5%) patients, including 375 (10.9%) MBG 0/1 patients, 475 (13.9%) MBG 2 patients, and 2,576 (75.2%) MBG 3 patients. Nonculprit MBG 0/1 was associated with worse baseline clinical characteristics. Patients with nonculprit MBG 0/1 versus MBG 3 had increased rates of 30-day (3.0% vs. 0.7%, p < 0.0001) and 1-year (4.4% vs. 1.0%, p < 0.0001) death. Similar results were found among patients with pre-procedural TIMI flow grade 3 in the culprit vessel, where nonculprit vessel MBG 0/1 (hazard ratio: 2.81 [95% confidence interval: 1.63 to 4.84], p = 0.0002) was the strongest predictor of 1-year mortality. CONCLUSIONS: Reduced myocardial perfusion in an area supplied by a nonculprit vessel is associated with increased short- and long-term mortality rates in NSTE-ACS patients undergoing PCI. Furthermore, worst nonculprit MBG is able to risk-stratify patients with normal baseline flow of the culprit vessel.

Automated 3D analysis of multislice computed tomography to define the line of perpendicularity of the aortic annulus and of the implanted valve: benefit on planning transcatheter aortic valve replacement.

AIMS: We aimed to determine whether preprocedural analysis of multislice computed tomography (MDCT) scan could accurately predict the "line of perpendicularity" (LP) of the aortic annulus and corresponding C-arm angulations required for prosthesis delivery. METHODS AND RESULTS: A 3D analysis of preprocedural MDCT dedicated to define the LP of the aortic annulus was performed in 60 consecutive patients referred for transcatheter aortic valve replacement (TAVR). In 24 patients, the analysis was performed retrospectively to evaluate reproducibility. In 11 patients of this cohort, additional fluoroscopy and MDCT were performed postprocedure to compare the LP of the aortic annulus and the LP of the implanted bioprosthesis. In 36 patients, the analysis was performed prospectively and the results were available at the time of the procedure. In those 36 patients, the postprocedure fluoroscopy-defined LP of the implanted bioprosthesis was used to validate the LP of the aortic annulus as predicted by MDCT. Intraobserver and interobserver reproducibility of the 3D analysis of MDCT to define the LP of the aortic annulus (κ = 1 and 0.94, respectively) and of the bioprosthesis (κ= 1 and 1, respectively) were excellent. Comparison between the LP of the aortic annulus and the LP of the bioprosthesis showed that the two LPs were virtually identical, demonstrating both self-centering of the device during implantation and the possibility to use the LP of the implanted bioprosthesis as a surrogate of the LP of the aortic annulus. In the prospective cohort, the ability of MDCT analysis to predict the LP of the aortic annulus was very good (accuracy = 94% and κ = 0.89). CONCLUSION: Automated 3D analysis of preimplantation MDCT accurately predicts the LP of the aortic annulus and the corresponding C-arm position required for TAVR.

The impact of the coronary collateral circulation on outcomes in patients with acute coronary syndromes: results from the ACUITY trial.

OBJECTIVE: We sought to assess the prognostic role of collaterals in a large population of patients presenting with an acute coronary syndrome (ACS). METHODS: The coronary collateral circulation was assessed by an independent angiographic core laboratory using the Rentrop Score in patients enrolled in the randomised Acute Catheterization and Urgent Intervention Triage Strategy trial. RESULTS: The cohort comprised 5412 patients with moderate to high risk ACS. A total of 858 patients (16.0%) had visible collaterals while 4554 patients (84.0%) had no collaterals. After multivariable adjustment, there were no differences in clinical outcomes at 1 year between the groups, including major adverse cardiac events (MACE) (HR 0.94 (95% CI 0.76 to 1.16), p=0.55), mortality (HR 1.03 (0.65 to 1.62), p=0.91), myocardial infarction (MI) (HR 1.07 (0.83 to 1.38), p=0.60) and unplanned target vessel revascularisation (TVR) (HR 0.95 (0.71 to 1.28), p=0.75). Similarly, in the subgroup of patients undergoing percutaneous coronary intervention (PCI), the adjusted HR for major adverse cardiac events was 1.1 (0.76 to 1.61), p=0.595; 0.81 (0.10 to 6.44), p=0.999 for mortality; and 0.86 (0.54 to 1.35), p=0.564 for MI. The risk of unplanned TVR was increased (HR 2.74 (1.48 to 5.10), p=0.004). CONCLUSIONS: In contrast to other studies, this large core laboratory-based analysis does not confirm a beneficial role of visible coronary collateral vessels on clinical outcomes in patients with ACS; the presence of collaterals was even associated with increased mortality in the unadjusted analysis. Collaterals were associated with a higher risk of TVR in patients undergoing PCI, a finding that may not have been fully corrected given confounders and clinical differences between the groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00093158.

Automated 3D analysis of pre-procedural MDCT to predict annulus plane angulation and C-arm positioning: benefit on procedural outcome in patients referred for TAVR.

OBJECTIVES: The aim of this study was to determine whether pre-procedural analysis of multidetector row computed tomography (MDCT) scans could accurately predict the "line of perpendicularity" (LP) of the aortic annulus and corresponding C-arm angulations required for prosthesis delivery and impact the outcome of the procedure. BACKGROUND: Optimal positioning of the transcatheter aortic prosthesis is paramount to transcatheter aortic valve replacement (TAVR) procedural success. METHODS: All patients referred for TAVR at our center underwent a routine pre-procedural MDCT scan. A 3-dimensional (3D) analysis using software dedicated to define the LP of the aortic annulus and the corresponding C-arm positioning was performed in 71 consecutive patients. In 35 patients, the results of the MDCT analysis were not available at the time of the procedure (angiography cohort). In that cohort the position of the C-arm was determined during the procedure using ad-hoc angiography. In 36 patients, the MDCT analysis was performed pre-procedure and results were available at the time of the procedure (MDCT cohort). In that cohort the position of the C-arm was derived from the MDCT analysis rather than by ad-hoc angiography. RESULTS: Intraobserver and interobserver reproducibility of MDCT analysis to predict the LP of the aortic annulus were excellent (kappa = 1 and 0.94, respectively). Patient variations of the LP ranged >70°. Compared with the angiography cohort, the MDCT cohort was associated with a significant decrease in implantation time (p = 0.0001), radiation exposure (p = 0.02), amount of contrast (p = 0.001), and risk of acute kidney injury (p = 0.03). Additionally, the combined rate of valve malposition and aortic regurgitation was also reduced (6% vs. 23%, p = 0.03). CONCLUSIONS: Automated 3D analysis of pre-implantation MDCT accurately predicts the LP of the aortic annulus and the corresponding C-arm position required for TAVR. With this approach, the implantation of the balloon-expandable prosthetic valve can be performed without an aortogram in the majority of cases and still be safe, with a low rate of valve malpositioning and regurgitation.

A prospective "oversizing" strategy of the Edwards SAPIEN bioprosthesis: results and impact on aortic regurgitation.

OBJECTIVE: Moderate to severe aortic regurgitation is occurring in 20% to 30% of cases after transcatheter aortic valve implantation. METHODS: The purpose of the study was to investigate the impact of a prospective policy of "oversizing" the Edwards SAPIEN bioprosthesis (Edwards Lifesciences LLC, Irvine, Calif) relative to the diameter of the aortic annulus on the rate and severity of aortic regurgitation in 28 consecutive patients initially considered eligible for transcatheter aortic valve implantation on the basis of angiography, multislice computed tomography, and transthoracic echocardiography. This policy included the systematic use of transesophageal echocardiography to exclude borderline patients and the modification of the procedure to use the larger device possible. The results were studied on an individual patient basis. RESULTS: Because 6 of 28 patients (21%) had an annulus diameter greater than 24 mm by transesophageal echocardiography, 22 patients underwent implantation of the Edwards SAPIEN prosthesis. In 6 of 22 patients, the procedure was adapted to follow our "oversizing" policy. As a result, the "prosthesis/annulus cover index" was 12.4% ± 4.3%. The procedure was successful in 21 of 22 patients (95%), and 18 patients were available for echocardiography at 1 month. Although a moderate to severe aortic regurgitation was observed pretreatment in 4 of 18 patients (22%), it was no longer the case at 1 month (0/18, 0%; P = .03). The improvement was secondary to a disappearance of the aortic regurgitation in all 7 patients with a significant aortic regurgitation at pretreatment, whereas the new aortic regurgitations appearing in 5 of the 11 patients with no aortic regurgitation at pretreatment were only mild aortic regurgitations. CONCLUSIONS: In patients with a successful implantation of an Edwards SAPIEN valve, a simple "oversizing" policy based on a systematic use of transesophageal echocardiography and modification of the procedure may prevent the occurrence of moderate and severe aortic regurgitations.

The Future REvascularization Evaluation in patients with Diabetes mellitus: optimal management of Multivessel disease (FREEDOM) trial: clinical and angiographic profile at study entry.

BACKGROUND: The optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD) remains uncertain for lack of an adequately powered, randomized trial. The FREEDOM trial was designed to compare contemporary coronary artery bypass grafting (CABG) to percutaneous coronary intervention (PCI) with drug-eluting stents in diabetic patients with MVD against a background of optimal medical therapy. METHODS: A total of 1,900 diabetic participants with MVD were randomized to PCI or CABG worldwide from April 2005 to March 2010. FREEDOM is a superiority trial with a mean follow-up of 4.37 years (minimum 2 years) and 80% power to detect a 27.0% relative reduction. We present the baseline characteristics of patients screened and randomized, and provide a comparison with other MVD trials involving diabetic patients. RESULTS: The randomized cohort was 63.1 ± 9.1 years old and 29% female, with a median diabetes duration of 10.2 ± 8.9 years. Most (83%) had 3-vessel disease and on average took 5.5 ± 1.7 vascular medications, with 32% on insulin therapy. Nearly all had hypertension and/or dyslipidemia, and 26% had a prior myocardial infarction. Mean hemoglobin A1c was 7.8 ± 1.7 mg/dL, 29% had low-density lipoprotein <70 mg/dL, and mean systolic blood pressure was 134 ± 20 mm Hg. The mean SYNTAX score was 26.2 with a symmetric distribution. FREEDOM trial participants have baseline characteristics similar to those of contemporary multivessel and diabetes trial cohorts. CONCLUSIONS: The FREEDOM trial has successfully recruited a high-risk diabetic MVD cohort. Follow-up efforts include aggressive monitoring to optimize background risk factor control. FREEDOM will contribute significantly to the PCI versus CABG debate in diabetic patients with MVD.

Measuring and targeting aldosterone and renin in atherosclerosis-a review of clinical data.

Our understanding of the development and progression of atherosclerosis has increased substantially over the past decades. A significant role for the renin-angiotensin-aldosterone system (RAAS) in this process has gained appreciation in recent years. Preclinical and clinical studies have associated components of the RAAS with various cardiovascular disease conditions. Classically known for its contribution to hypertension, dysregulation of the system is now also believed to promote vascular inflammation, fibrosis, remodeling, and endothelial dysfunction, all intimately related to atherosclerosis. The reduction in cardiovascular mortality and morbidity, as seen with the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, supports the concept that RAAS is involved in the pathogenesis of atherosclerotic disease. However, the underlying molecular mechanisms of the pathophysiology remain to be completely understood. Evidence points toward additional benefit from therapeutic approaches aiming at more complete inhibition of the system and the possible utility of renin or aldosterone in the prediction of cardiovascular outcome. This review will summarize the current knowledge from clinical studies regarding the presumptive role of renin and aldosterone in the prediction and management of patients with atherosclerosis. For this purpose, a literature search was performed, focusing on available clinical data regarding renin or aldosterone and cardiovascular outcome.

Prognostic significance of coronary thrombus in patients undergoing percutaneous coronary intervention for acute coronary syndromes: a subanalysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.

OBJECTIVES: The objective of this study is to investigate the incidence and clinical implications of thrombus on baseline angiography among patients presenting with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Given current advances in the pharmacological and mechanical treatment of ACS patients managed with an early invasive strategy, the incidence and prognostic importance of pre-procedural lesion thrombus is warranted. METHODS: In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, a total of 3,627 patients with moderate- and high-risk ACS undergoing PCI had their baseline and final post-PCI angiograms analyzed by an independent angiographic core laboratory. RESULTS: Patients with thrombus (n = 530 [15%]) compared with those without thrombus had higher rates of impaired final epicardial coronary flow (final Thrombolysis In Myocardial Infarction [TIMI] flow grade 3: 89.6% vs. 97.1%, p < 0.0001). Thrombus was an independent predictor of 30 day death (odds ratio [OR]: 3.16 [95% confidence interval (CI): 1.20 to 8.37], p = 0.02), and myocardial infarction (MI) at 30 days (OR: 1.62 [95% CI: 1.17 to 2.24], p = 0.003) and at 1 year (OR: 1.56 [95% CI: 1.16 to 2.08], p = 0.003). Patients with thrombus had significantly higher rates of stent thrombosis (ST) compared with patients without thrombus at 30 days (2.8% vs. 1.1%, p = 0.002) and at 1 year (3.7% vs. 1.8%, p = 0.003), and thrombus was an independent predictor of ST at both 30 days (OR: 2.61 [95% CI: 1.38 to 4.91]) and 1 year (OR: 2.98 [95% CI: 1.64 to 5.42]). CONCLUSIONS: Pre-procedural thrombus was present in 15% of moderate- and high-risk ACS patients undergoing PCI in the ACUITY trial. Baseline thrombus predicts increased ischemic complications at 30 days including a 3-fold increased risk of death as well as MI up to 1 year. Further evaluation of adjunctive pharmacotherapy is needed in this high-risk population.

Predictive value of C-reactive protein on 30-day and 1-year mortality in acute coronary syndromes: an analysis from the ACUITY trial.

We sought to evaluate the association between C-reactive protein (CRP) sampled on admission and short- and long-term mortality in patients with acute coronary syndromes (ACS) undergoing early invasive treatment. Baseline levels of CRP were determined in 2,974 patients with moderate and high-risk ACS undergoing an early invasive treatment strategy in the large-scale randomized ACUITY trial. The relationship of CRP to 30-day and 1-year clinical outcomes were assessed according to quartiles of CRP values. Patients with CRP levels in the fourth quartile compared to the first quartile had significantly higher 30-day mortality (2.3 vs. 0.3%, P = 0.0004) and 1-year mortality (5.5 vs. 2.8%, P = 0.0003). CRP level as a continuous variable was associated with 30-day mortality (OR [95% CI] for one unit increase in logarithmically transformed CRP level = 1.42 [1.08-1.89], P = 0.01) and 1-year mortality (OR [95% CI] = 1.24, [1.04-1.47], P = 0.02). By multivariable analysis, higher baseline CRP levels independently predicted 30-day and 1-year mortality, a relationship that was particularly strong for patients with the highest quartile of CRP (OR [95% CI] = 5.19 [1.14-23.68], P = 0.009). In troponin-positive patients, increasing quartiles of CRP were associated with a trend for 30-day mortality (P (trend) = 0.08) and a significant increase in 1-year mortality (P (trend) = 0.02); this relationship was not present in troponin-negative patients. Baseline CRP level is a powerful independent predictor of both early and late mortality in patients with ACS being treated with an early invasive strategy, especially in troponin positive patients.

Impact of chronic antiplatelet therapy before hospitalization on ischemic and bleeding events in invasively managed patients with acute coronary syndromes: the ACUITY trial.

AIMS: Presentation with an acute coronary syndrome (ACS) on chronic aspirin therapy is an independent predictor of adverse short-term outcomes. Whether this finding applies to chronic thienopyridine use, and with the contemporary invasive management of ACS, is unknown. METHODS AND RESULTS: In ACUITY, 13819 patients with moderate and high-risk ACS were studied; patients transferred from an outside hospital were excluded from the present analysis, given uncertain preadmission antiplatelet status. Endpoints included major adverse cardiovascular events (MACE: death, myocardial infarction, or unplanned revascularization), major bleeding, and net adverse clinical events (NACE). Among 11313 study patients, 31 % were naive for antiplatelet agent, 49% were receiving aspirin alone, and 20% were on dual antiplatelet therapy. Chronic antiplatelet users were older and had a higher risk profile. After adjusting for baseline differences, chronic antiplatelet therapy (single or dual) was not associated with an increased incidence of 30-day MACE, bleeding, or NACE. However, patients on chronic aspirin or dual antiplatelet therapy at presentation had significantly higher 1-year rates of MACE [odds ratio (95% confidence interval) = 1.17 (1.01­1.36), P = 0.03 and 1.29 (1.02­1.64), P = 0.03, respectively]. Patients presenting on dual antiplatelet therapy had significantly greater adjusted MACE at 1-year than those on aspirin alone [odds ratio (95% confidence interval) = 1.34 (1.15­1.56), P < 0.0001]. CONCLUSION: Contrary to earlier studies, prior antiplatelet therapy was not associated with an increased risk of adverse outcomes at 30 days in invasively managed patients. Such use did, however, independently predict 1-year ischemic MACE, with outcomes worse for patients presenting on chronic dual antiplatelet therapy compared with aspirin alone.

Comparison of catheterization laboratory initiated abciximab and eptifibatide during percutaneous coronary intervention in acute coronary syndromes (an ACUITY substudy).

Abciximab and eptifibatide have been shown to reduce ischemic complications compared with heparin alone in patients with acute coronary syndromes who undergo percutaneous coronary intervention. Whether 1 agent is safer and/or more effective has not been prospectively examined. The aim of this study was to assess the outcomes related to downstream glycoprotein IIb/IIIa inhibitor treatment selection during percutaneous coronary intervention in 2,211 patients with moderate and high-risk acute coronary syndromes in the prospective multicenter Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. The protocol permitted operator selection of abciximab (n = 835) or eptifibatide (n = 1,376) for routine use in the trial. Multivariate and propensity-based adjustments were used to assess the independent association of glycoprotein IIb/IIIa inhibitor treatment selection with prespecified study end points. Compared to patients receiving eptifibatide, those administered abciximab were older, more likely to be enrolled outside of North America, more frequently had biomarker elevations and ST-segment deviation, but had fewer baseline cardiac risk factors and previous revascularization procedures. After multivariate propensity-based adjustment, abciximab was independently associated with significantly fewer net clinical adverse events (odds ratio 0.61, 95% confidence interval 0.42 to 0.90, p = 0.01), mediated by composite ischemia (odds ratio 0.61, 95% confidence interval 0.38 to 0.98, p = 0.04) and major bleeding (odds ratio 0.58, 95% confidence interval 0.34 to 1.00, p = 0.051). In conclusion, in this prespecified but nonrandomized comparison in patients with acute coronary syndromes who underwent percutaneous coronary intervention with catheterization laboratory initiation of glycoprotein IIb/IIIa inhibitors, the use of abciximab rather than eptifibatide was associated with improved clinical outcomes at 30 days. These findings should be viewed as exploratory in light of the nonrandomized and heterogeneous nature of the comparator groups and significant potential for residual confounding.