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Studies have linked on-treatment platelet reactivity (PR) to adverse clinical outcomes. Because new P2Y12 inhibitors (prasugrel and ticagrelor) have been predominantly tested against clopidogrel, data on pharmacodynamic comparisons between these 2 drugs are scarce. We compared ticagrelor with prasugrel in a network meta-analysis. PubMed, Cochrane, and EMBASE were searched for studies assessing PR in patients with coronary artery disease treated with ticagrelor or prasugrel. All studies using prasugrel and/or ticagrelor providing platelet function measurement data using VerifyNow P2Y12 reaction units (PRUs), platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein phosphorylation, or maximal platelet aggregation (MPA) by light transmission aggregometry were considered eligible. Mixed treatment comparison models directly compared ticagrelor and prasugrel and indirectly compared them using clopidogrel as a comparator with data presented as mean difference (95% confidence interval). Data were extracted from 29 studies, including 5,395 patients. Compared with clopidogrel 75 mg, both prasugrel 10 mg and ticagrelor 90 mg twice daily were associated with lower PRU (mean difference -117 [-134.1, -100.5] and -159.7 [-182.6, -136.6], respectively), a lower PRI (-24.2 [-28.2, -20.3] and -33.6 [-39.9, -27.6], respectively), and lower MPA (-11.8 [-17, -6.3] and -20.7 [-28.5, -12.8], respectively). Similar results were obtained with clopidogrel 150 mg. Ticagrelor 90 mg twice daily was associated with lower PRU (-42.5 [-62.9, -21.9]), lower PRI (-9.3 [-15.6, -3.5]), and lower MPA (-8.9 [-16.4, -1.2]) compared with prasugrel 10 mg. In conclusion, our meta-analysis suggests that ticagrelor achieved significantly lower on-treatment PR compared with prasugrel, with both being superior to clopidogrel standard or high dose. [ABSTRACT FROM AUTHOR]

Baseline anemia is associated with transfusions and increased risk of mortality in patients who underwent cardiac surgery and percutaneous coronary intervention. The impact of blood transfusions in anemic patients who underwent transcatheter aortic valve implantation (TAVI) remains unclear. All patients who underwent transfemoral TAVI at our institution were retrospectively included. We determined the effect of blood transfusions on short- and long-term mortality and its interaction with baseline hemoglobin levels and bleeding complications. Additionally, we evaluated baseline hemoglobin effect on mortality. A total of 332 patients were included. All patients (99%) except 2 (1%) met the definition for anemia. Of the 332 patients, 124 (37%) received a blood transfusion and 208 (63%) did not. Blood transfusions were associated with increased in-hospital (p <0.001), 30-day (p <0.001), and 1-year (28% vs 13%, p = 0.001) mortality; however, after a landmark analysis, the effect of blood transfusion on mortality was only seen within 30 days of the procedure (p = 0.001). The increased risk of mortality associated with blood transfusion was present after multivariate adjustment at 30 days (hazard ratio 3.59 [1.04 to 12.4]; p = 0.04). Major vascular complications were a correlate for short- and long-term death. In contrast, baseline hemoglobin level and bleeding complications were not independently associated with mortality. The p value for interaction was not significant between transfusion and hemoglobin level and for transfusion and bleeding complication and transfusion and major vascular complication. In conclusion, the presence of anemia in patients who underwent TAVI does not affect mortality. Transfusion is a correlate of all-cause mortality in this patient population and should be used with caution. [ABSTRACT FROM AUTHOR]

Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/ PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p = 0.67). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department. [ABSTRACT FROM AUTHOR]

A consensus on what constitutes a clinically meaningful periprocedural myocardial infarction (PMI) remains highly debated. We evaluated the accuracy of 2 PMI definitions currently implemented for quality outcome assessment and clinical trial end points. Patients who underwent elective percutaneous coronary intervention with normal baseline troponin- I and creatine kinase-MB were included. PMI was defined according to either the 2007 Task Force (National Cardiovascular Database Registry [NCDR] CathPCI Registry) definition or the updated 2012 Task Force definition. Multivariate analysis was performed for the end point of 1-year all-cause death or myocardial infarction (MI). Of the 7,333 patients included, 31.9% and 2.1% were identified as having a PMI by NCDR or 2012 definition, respectively. Mean age was 66 - 11 years; 66.8% were men, 1.4 - 0.9 stents implanted per patient, 84.5% bivalirudin use, and 29.7 type C lesions. Death or MI occurred in 5.6% of NCDR and 6.6% of 2012 defined patients. Neither biomarker was independently associated with death or MI for either definition (NCDR odds ratio 1.1, 95% confidence interval 0.9 to 1.5, p[0.34; 2012 Task Force odds ratio 1.4, 95% confidence interval 0.7 to 3.0, p[0.38). Only a modest correlation exists for either definition to predict death or MI, which did not improve for the 2012 definition. In conclusion, PMI definitions currently used for catheterization lab quality metrics and those used for clinical trial end points have poor discrimination for adverse events. Although the 2012 definition drastically reduced the number of PMIs defined, it did not decrease the predictive accuracy over the NCDR definition. [ABSTRACT FROM AUTHOR]

Although statins have been shown to improve outcomes in retrospective analyses of patients with heart failure (HF), recent randomized placebo-controlled trials have shown mixed results. The goal of this study was to systematically review randomized trials comparing statins to placebo for HF and compare the impact of different statins. CENTRAL, mRCT, and PubMed were searched for eligible studies that prospectively randomized patients with HF to statins or placebo. Primary end points were all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, adverse drug events, and changes in left ventricular ejection fraction (LVEF). Pooling was performed with random effect methods with summary effect estimates (95% confidence intervals). Ten studies (10,192 patients) with follow-up from 3 to 47 months were included. Three trials randomized patients to rosuvastatin, 1 to simvastatin, and 6 to atorvastatin. Overall, statins did not affect all-cause or cardiovascular mortality but did significantly decrease hospitalization for worsening HF during follow-up (odds ratio [OR] 0.67, p = 0.008). Patients randomized to statins had a significant 4.2% increase in LVEF at follow-up (95% confidence interval 1.3 to 7.1, p = 0.004). Furthermore, post hoc analyses showed heterogeneity among different statins and demonstrated that randomization to atorvastatin significantly decreased all-cause mortality (OR 0.39, p = 0.004), decreased hospitalization for worsening HF (OR 0.30, p <0.000 01), and randomization to atorvastatin and simvastatin led to a significant improvement in LVEF, whereas these benefits were not observed in patients randomized to rosuvastatin. In conclusion, meta-analysis of randomized controlled trials demonstrated that statins are safe and improve LVEF and decrease hospitalization for worsening HF. [Copyright &y& Elsevier]

Recent studies have reported a higher incidence of late stent thrombosis in patients undergoing drug-eluting stent (DES). Reduced left ventricular (LV) ejection fraction (EF) is considered a risk factor for this complication after both bare-metal stent (BMS) and DES implantation. Therefore, the aim of this study was to evaluate the safety of DES on long-term follow-up in patients with LV dysfunction undergoing percutaneous coronary intervention. We retrospectively selected all patients with an EF <45% undergoing percutaneous coronary intervention with implantation of ≥1 sirolimus- or paclitaxel-eluting stent at our institution. The primary endpoint of the study was all-cause mortality, retrieved using both Social Security Database and hospital records. We also compared the results of this group with a historical cohort of patients with LV dysfunction undergoing BMS implantation; 121 patients who received ≥1 DES were enrolled. The mean LVEF was 36 ± 8%, with 20 patients (16%) with a LVEF ≤25%; 36 patients (30%) had diabetes mellitus, and DES implantation was considered off-label in 100 patients (83%). Survival at 1-, 2-, and 3-year follow-up was 94% (95% confidence interval [CI] 88 to 100), 90% (95% CI 82 to 98) and 88% (95% CI 80 to 96), respectively. In conclusion, the favorable results of this study demonstrate the safety of DES in patients with LV dysfunction. [Copyright &y& Elsevier]

Patients with chronic kidney disease and heart failure (HF) have been shown to be at higher risk for major adverse cardiovascular events and death. Recent studies have demonstrated that blood urea nitrogen (BUN) might serve as a powerful predictor of mortality in acutely decompensated HF. The goal of this study was to determine the impact of BUN on long-term mortality in patients with stage B and C HF. Our retrospective analysis included patients undergoing percutaneous intervention with a calculated left ventricular ejection fraction ≤50%. Patients on dialysis or with technically inadequate left ventriculograms were excluded. Chart review was performed and mortality data were obtained. Our population included 444 patients with a mean ejection fraction of 38 ± 10%, mean age of 59 ± 11 years, median BUN of 14 mg/dl, and median glomerular filtration rate (GFR) of 81 ml/min/1.73 m2; 31% had stage C HF, and 33% died during follow-up. Patients with increased BUN (≥17 mg/dl) and decreased GFR (≤69 ml/min/1.73 m2) had significantly increased long-term mortality on Kaplan-Meier analysis (8-year mortalities of 57% and 55%, respectively). In patients with stage C HF, mortalities at 8 years were 69% and 73% with abnormal BUN and GFR, respectively. Proportional hazard regression analysis demonstrated that BUN and stage C HF were independently associated with increased mortality, whereas GFR was not. In conclusion, we demonstrated that BUN is strongly associated with mortality in patients with stage B and C HF and may serve as a better biomarker than GFR for prognostication. [Copyright &y& Elsevier]

We retrospectively analyzed exercise treadmill and coronary angiographic data of 2,193 men to compare heart rate (HR) recovery with angiographic and mortality data during a follow-up study of 7 ± 2.7 years. Only the first 2 minutes of HR recovery predicted mortality (p <0.001), and the HR decrease during the second minute of recovery predicted the presence of coronary artery disease (p <0.05). [Copyright &y& Elsevier]

Although metallic coronary stents significantly reduce angina pectoris compared with optimal medical therapy, angina after percutaneous coronary intervention (PCI) remains frequent. We, therefore, sought to compare the incidence of any angina during the 1 year after PCI among the spectrum of commercially available metallic stents. Metallic stent type was classified as bare metal stent, Cypher, Taxus Express, Xience V, Promus Element, and Resolute. The primary end point was patient-reported angina within 1 year of PCI. Multivariable logistic regression was performed to assess the independent association of stent type with any angina at 1 year. Overall, 8,804 patients were queried in regard to angina symptoms; 32.3% experienced angina at some point in the first year after PCI. Major adverse cardiovascular events, a composite of all-cause mortality, target vessel revascularization, and Q-wave myocardial infarction, increased with angina severity: 6.8% for patients without angina, 10.0% for patients with class 1 or 2 angina, and 19.7% for patients with class 3 or 4 angina (p <0.001 for trend). After multivariable adjustment, there was no significant association between stent type and angina at 1 year after PCI. Baseline Canadian Cardiovascular Society class 3 or 4 angina, history of coronary artery bypass grafting, and history of PCI were associated with a higher likelihood of angina at 1 year; increasing age, male gender, presentation with acute coronary syndrome, and higher stented length were associated with less angina. In conclusion, metallic stent type is not associated with the occurrence of angina at up to 1 year after PCI. [ABSTRACT FROM AUTHOR]

The effect of left atrial (LA) structural remodeling and dilatation on the outcome of ablation of atrial fibrillation (AF) remains unknown. We correlated potential prognostic markers of AF ablation, including LA volume from computed tomography, with AF recurrence after ablation. We studied 73 consecutive patients (52 with paroxysmal AF, 21 with persistent AF) undergoing AF ablation. LA volume was calculated by axial slice summation from 3-dimensional computed tomography. Follow-up was through 12 months, with success of ablation determined by electrocardiography and lack of symptoms (unless symptoms proved not AF by Holter monitor). Overall procedure success was 66% (including 15% repeat ablations, 12% on antiarrhythmics). Pulmonary vein isolation was performed, with additional linear ablation in 44 (60%). Mean LA volume (95% confidence interval) for those with recurrent AF was 119 ml (104 to 135) versus 98 ml (90 to 106) for no recurrence (p = 0.01, rank-sum test). Wide variation in LA volume occurred in the 2 groups, but, of the 15% of patients with very large LA volumes (>135 ml), 82% had recurrent AF. A cutpoint of 135 ml yields 36% sensitivity and 96% specificity for recurrence. In multivariable regression analysis, only LA volume and number of cardiovascular co-morbidities were associated with more recurrence (p = 0.02 and p = 0.03, respectively). In conclusion, LA volume varies greatly in those with and without successful AF ablations, mean LA volume is significantly larger in those with recurrence, and patients with LA volumes >135 ml are very likely to develop recurrent AF. [Copyright &y& Elsevier]

Patients with diabetes mellitus are prone to increased adverse outcomes after percutaneous coronary intervention, even with contemporary drug-eluting stents. Randomized controlled trials have demonstrated comparable clinical outcomes between an ultrathin bioresorbable-polymer sirolimus-eluting stent (BP-SES) and a thin-strut durable-polymer everolimus-eluting stent (DP-EES) that has specific labeling for patients with diabetes. We aimed to evaluate the safety and efficacy of the BP-SES in patients with diabetes mellitus. To determine the performance of the BP-SES in diabetic patients, patient-level data from the BIOFLOW II, IV, and V randomized controlled trials were pooled. The primary end point was target lesion failure (TLF), defined as the composite of cardiovascular death, target-vessel myocardial infarction, ischemia-driven target lesion revascularization, and definite or probable stent thrombosis, at 1 year. Among 1,553 BP-SES and 791 DP-EES patients, 757 diabetic patients were identified. Of the diabetic patients included in this analysis (494 BP-SES vs 263 DP-EES), the proportion of insulin- and noninsulin-treated patients was similar between groups. The 1-year TLF rate in the diabetic population was 6.3% in the BP-SES group and 8.7% in the DP-EES group (hazard ratio 0.82, 95% confidence interval 0.047 to 1.43, p = 0.493). There were no significant differences, based on stent type or diabetes treatment regimen, in TLF hazards. In a patient-level pooled analysis of the diabetic population from randomized trials, 1-year clinical safety and efficacy outcomes were similar in patients treated with ultrathin BP-SES and thin-strut DP-EES., (Copyright © 2019. Published by Elsevier Inc.)

The aim of this network meta-analysis is to assess the impact of strut thickness on clinical outcomes in patients who underwent percutaneous coronary intervention. We searched Medline/PubMed and performed a Bayesian network meta-analysis to compare outcomes of patients who underwent percutaneous coronary intervention with drug-eluting stents (DES) of different strut thicknesses (ultrathin 60 to 80 μm; thin 81 to 100 μm; intermediate 101 to 120 μm; thick ≥120 μm). Studies comparing DES with similar strut thickness, bare metal stents, and fully bioresorbable scaffolds were excluded. Odds ratios with credible intervals (OR [CrIs]) were generated with random-effects models to compare outcomes. Our primary end point was stent thrombosis (ST). We identified 69 RCTs including 80,885 patients (ultrathin group = 10,219; thin group = 36,575; intermediate group = 11,399; thick group = 22,692). Mean age was 64 ± 11 years and 75% were male gender. When compared with thick-strut DES, ultrathin struts had significant less ST and myocardial infarction (OR 0.43 [CrI 0.27 to 0.68]; and OR 0.73 [CrI 0.62 to 0.92], respectively). Sensitivity analysis including only studies with permanent polymer DES gave similar results. Improvement in DES technology with thinner struts is associated with significant reduction in ST and myocardial infarction compared with thicker struts., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Permanent pacemaker (PPM) implantation remains common after transcatheter aortic valve implantation (TAVI). Invasive electrophysiology studies (EPSs) may reduce PPM implantation rates by identifying patients who do not require long-term pacing. At our institution, a new strategy in which patients with equivocal indications for pacing underwent EPSs to determine the need for PPM implantation was adopted. We compared baseline demographics, TAVI procedural details, and outcomes in patients without any conduction disturbance after TAVI, patients with new PPM implantation, and patients with EPS ± new PPM implantation. After exclusion for preexisting PPMs, of a total of 614 consecutive TAVI patients, 117 (19.1%) required new PPM implantation for unequivocal pacing indications, and 95 (15.5%) underwent EPSs. Of those patients who underwent EPSs, 28 (29.5%) required PPM implantation and 67 (70.5%) did not. The overall rate of new PPM implantation was higher for self-expanding versus balloon-expandable valves (34.0% vs 19.9%, p = 0.0011). PPM implantation increased intensive care and hospital length of stay compared with patients without any conduction disturbance (10.7 ± 8.3 vs 8.5 ± 6.4 days, p = 0.003). A negative EPS did not prolong length of stay. There were no significant differences in 30-day and 1-year mortality between groups. In conclusion, among TAVI patients with new-onset conduction disturbance, EPS is a safe strategy to identify those who require PPM implantation and those in whom PPMs can be avoided., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Patients at high bleeding risk (HBR) are at increased risk of bleeding following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) due to the need for longer dual antiplatelet duration. We sought to evaluate the likelihood of receiving DES during PCI in HBR populations and to characterize DES utilization trends over time. Consecutive patients who underwent PCI from April 2003 to September 2015 were identified. HBR is defined as patients fulfilling 1 or more of the HBR criteria: age ≥75 years, anticoagulation use at discharge, history of stroke, cancer in previous 3 years, glucocorticoid use, hemoglobin (Hgb) <11 g/dl, platelet count <100,000/mm 3 , or creatinine clearance (CCr) <40 ml/min. Multivariate analysis was performed to identify which variables predicted DES selection. There were 10,594 patients (41.6%) who the met HBR definition. When adjusting for known risk factors, HBR patients were less likely to receive a DES compared with non-HBR patients (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.54 to 0.62, p <0.001). A preprocedural Hgb <11 g/dl had the greatest association with choosing DES during PCI (OR 0.51, 95% CI 0.45 to 0.57, p <0.001). Within the HBR patients, having 3 or more HBR criteria versus <3 HBR criteria had lower likelihood of receiving a DES (OR 0.50, 95% CI 0.44 to 0.57, p <0.001). In conclusion, presence of HBR has a significant impact upon the decision to use DES., (Copyright © 2017 Elsevier Inc. All rights reserved.)

With steady growth in the use of drug-eluting stents (DES), the indications for bare metal stents (BMS) have significantly changed over the last decade. This study aims to describe trends in the use of BMS and the evolution of the population receiving them over the past 10 years and determine patient characteristics associated with using BMS. Consecutive patients who underwent percutaneous coronary intervention (PCI) at the Washington Hospital Center from January 2005 through March 2015 were included. Baseline characteristics and inhospital outcomes of patients who underwent PCI with BMS versus DES were compared during 2 different time periods: from 2005 to 2010 and from 2011 to 2015. Multivariable analyses were performed for each period of time to determine independent variables associated with the choice of BMS rather than DES; 20,321 patients who underwent PCI were included in the present study. The mean age was 65.0 ± 12.5 years, 65.2% were men, and 30.4% were black. BMS use peaked in 2007 (47%) but has fallen steadily since; BMS accounted for only 10% of stents used in 2015. Presentation with acute coronary syndrome or cardiogenic shock was more common in patients receiving a BMS; this was reflected in higher rates of inhospital mortality and major bleeding among patients receiving BMS versus DES. Covariables independently associated with receiving a BMS common to both time periods included black race, Hispanic ethnicity, cardiogenic shock or acute coronary syndrome, oral anticoagulation, current smoking, increasing age, lower hematocrit, and history of chronic renal insufficiency. In conclusion, there has been a precipitous decline in the use of BMS over the last decade. Newer stent technology that promises shorter duration of dual antiplatelet therapy is likely to lead to the extinction of BMS over the next decade., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 μmol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 ± 65 vs 198 ± 86, p <0.001) and vasodilator-stimulated phosphoprotein (12.8 ± 21.6 vs 58.9 ± 19.9, p <0.001) at 1 hour compared with those with no clopidogrel preload. In conclusion, among patients with ACS receiving ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Transcatheter aortic valve implantation (TAVI) decreases mortality in high-risk patients with severe aortic stenosis, but it remains unclear if female gender is associated with more favorable outcomes after TAVI. All patients who underwent TAVI at a single institution were retrospectively analyzed and stratified by gender. Procedural, in-hospital, 30-day, and 1-year outcomes were defined according to the second Valve Academic Research Consortium. The primary end point was all-cause mortality at 1 year. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were conducted. Overall, 755 patients underwent TAVI and were included in the study; 50.7% were women. Average age was 83.0 ± 7.7 years, with a mean Society of Thoracic Surgeons score of 8.9 ± 4.6. Women were older than men and more likely to be black. Most co-morbidities were less common among women, and they were more likely than men to suffer both in-hospital (8.4% vs 4.3%, p = 0.021) and 30-day (9.4% vs 5.4%, p = 0.035) all-cause mortality. Life-threatening bleeding, transfusion, and iliofemoral dissection or perforation were more common among women. There was no difference in mortality between women and men at 1 year (20.6% vs 21.5%, log-rank p = 0.87). After multivariable adjustment, however, female gender was independently associated with lower mortality at 1 year after TAVI. In conclusion, despite higher rates of major bleeding, vascular complications, and 30-day mortality, female gender was independently associated with improved survival at 1 year after TAVI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We sought to compare the diagnostic performance of coronary computed tomography angiography (CCTA), computed tomography perfusion (CTP), and computed tomography (CT)-fractional flow reserve (FFR) for assessing the functional significance of coronary stenosis as defined by invasive FFR in patients with known or suspected coronary artery disease (CAD). CCTA has proved clinically useful for excluding obstructive CAD because of its high sensitivity and negative predictive value (NPV); however, the ability of CTA to identify functionally significant CAD has remained challenging. We searched PubMed/Medline for studies evaluating CCTA, CTP, or CT-FFR for the noninvasive detection of obstructive CAD compared with catheter-derived FFR as the reference standard. Pooled sensitivity, specificity, PPV, NPV, likelihood ratios, and odds ratio of all diagnostic tests were assessed. Eighteen studies involving a total of 1,535 patients were included. CTA demonstrated a pooled sensitivity of 0.92, specificity 0.43, PPV of 0.56, and NPV of 0.87 on a per-patient level. CT-FFR and CTP increased the specificity to 0.72 and 0.77, respectively (p = 0.004 and p = 0.0009) resulting in higher point estimates for PPV 0.70 and 0.83, respectively. There was no improvement in the sensitivity. The CTP protocol involved more radiation (3.5 mSv CCTA vs 9.6 mSv CTP) and a higher volume of iodinated contrast (145 ml). In conclusion, CTP and CT-FFR improve the specificity of CCTA for detecting functionally significant stenosis as defined by invasive FFR on a per-patient level; both techniques could advance the ability to noninvasively detect the functional significance of coronary lesions., (Copyright © 2015 Elsevier Inc. All rights reserved.)