Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Design and rationale of the randomized trial of comprehensive lifestyle modification, optimal pharmacological treatment and utilizing PET imaging for quantifying and managing stable coronary artery disease (the CENTURY study).

BACKGROUND: The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice. METHODS: The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization. CONCLUSIONS: The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.

Regional, Artery-Specific Thresholds of Quantitative Myocardial Perfusion by PET Associated with Reduced Myocardial Infarction and Death After Revascularization in Stable Coronary Artery Disease.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest-stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET (P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size-severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone.

Clinical Utility of Enhanced Relative Activity Recovery on Systolic Myocardial Perfusion SPECT: Lessons from PET.

UNLABELLED: SPECT and PET myocardial perfusion images show greater myocardial intensity and homogeneity in systole than diastole because of greater systolic myocardial thickness, less partial volume loss, and enhanced activity recovery. Consequently, conventional myocardial perfusion images obtained from whole cardiac cycles have lower myocardial intensity and greater heterogeneity than systolic images. Considering relative activity distribution on SPECT systolic images may add clinical utility to whole-cycle images and wall motion. METHODS: Patients undergoing coronary angiogram within 4 mo after SPECT myocardial perfusion imaging were reviewed. Images were interpreted by 2 masked interpreters using a 17-segment, 5-point scale to determine summed rest scores (SSS), summed stress scores, and summed difference scores on conventional and systolic images in 603 patients (55.6% no coronary artery disease [no-CAD] and 44.4% CAD). Studies were considered normal when the SSS was less than 4 and summed difference score was less than 2. RESULTS: In the no-CAD group, systolic SSS was lower than SSS from conventional images (2 ± 2.3 vs. 3 ± 2.6, P < 0.001). In contrast, SSS derived from systolic and conventional images were not different in the obstructive CAD group (9.1 ± 7.6 vs. 9.2 ± 7.4, P = 0.559). When systolic images were considered, true-negative studies increased from 27.2% to 43.3% (P < 0.001) whereas false-positive studies decreased from 28.4% to 12.3% (P < 0.001). True-positive (38% vs. 37.2%, P = 0.505) and false-negative studies (6.5% vs. 7%, P = 0.450) were not significantly changed. Diagnostic accuracy increased from 65.2% to 80.8% (P < 0.001). CONCLUSION: For gated SPECT myocardial perfusion imaging, when relative activity distribution on systolic images was considered, false-positive studies were reduced and diagnostic accuracy was improved.

Comparison of outcomes for patients ≥75 years of age treated with pre-hospital reduced-dose fibrinolysis followed by percutaneous coronary intervention versus percutaneous coronary intervention alone for treatment of ST-elevation myocardial infarction.

A coordinated system of care for patients with ST-segment elevation myocardial infarctions that includes prehospital administration of reduced-dose fibrinolytic agents coupled with urgent percutaneous coronary intervention (PCI), termed FAST-PCI, has been shown to be at least as effective as primary PCI (PPCI) alone. However, this reduced-dose fibrinolytic strategy could be associated with increased bleeding risk, especially in elderly patients. The purpose of this study was to examine 30-day outcomes in patients aged ≥75 years with ST-segment elevation myocardial infarctions treated with either strategy. Data from 120 patients aged ≥75 years treated with FAST-PCI were compared with those of 94 patients aged ≥75 years treated with PPCI. The primary comparator was mortality at 30 days. Stroke, reinfarction, and major bleeding were also compared. The groups were well matched for age, cardiac risk factors, and ischemic times. At 30 days, mortality was lower with FAST-PCI than with PPCI (4.2% vs 18.1%, p <0.01). Rates of stroke, reinfarction, and major bleeding (4% vs 2%) were similar in the 2 groups. The FAST-PCI cohort had lower rates of cardiogenic shock on hospital arrival (15% vs 26%, p = 0.05) and completely occluded infarct arteries (Thrombolysis In Myocardial Infarction [TIMI] grade 0 flow, 35% vs 61%, p <0.01). In conclusion, for patients aged ≥75 years with ST-segment elevation myocardial infarctions, a FAST-PCI strategy in a coordinated system of care was associated with reduced 30-day mortality, earlier infarct artery patency, and lower incidence of cardiogenic shock at arrival compared with PPCI, without apparent bleeding, stroke, or reinfarction penalties.

Cost analysis of PET and comprehensive lifestyle modification for the reversal of atherosclerosis.

UNLABELLED: We present a preliminary cost analysis of a combination intervention using PET and comprehensive lifestyle modification to reverse atherosclerosis. With a sensitivity of 92%-95% and specificity of 85%-95%, PET is an essential tool for high-precision diagnosis of coronary artery disease, accurately guiding optimal treatment for both symptomatic and asymptomatic patients. PET imaging provides a powerful visual and educational aid for helping patients identify and adopt appropriate treatments. However, little is known about the operational cost of using the technology for this purpose. METHODS: The analysis was done in the context of the Century Health Study for Cardiovascular Medicine (Century Trial), a 1,300-patient, randomized study combining PET imaging with lifestyle changes. Our methodology included a microcosting and time study focusing on estimating average direct and indirect costs. RESULTS: The total cost of the Century Trial in present-value terms is $9.2 million, which is equal to $7,058 per patient. Sensitivity analysis indicates that the present value of total costs is likely to range between $8.8 and $9.7 million, which is equivalent to $6,655-$7,606 per patient. CONCLUSION: The clinical relevance of the Century Trial is significant since it is, to our knowledge, the first randomized controlled trial to combine high-precision imaging with lifestyle strategies. The Century Trial is in its second year of a 5-y protocol, and we present preliminary findings. The results of this cost study, however, provide policy makers with an early estimate of the costs of implementing, at large scale, a combined intervention such as the Century Trial. Further, we believe that imaging-guided lifestyle management may have considerable potential for improving outcomes and reducing health-care costs by eliminating unnecessary invasive procedures.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Comparison of in-hospital outcomes with low-dose fibrinolytic therapy followed by urgent percutaneous coronary intervention versus percutaneous coronary intervention alone for treatment of ST-elevation myocardial infarction.

In patients with acute ST-elevation myocardial infarction (STEMI), a strategy of prehospital reduced dose fibrinolytic administration coupled with urgent percutaneous coronary intervention (PCI), termed FAST-PCI strategy, has been found to be superior to primary PCI (PPCI) alone. A coordinated STEMI system of care that includes FAST-PCI should offer better outcomes than a system in which prehospital diagnosis of STEMI is followed by PPCI alone. The aim of this study was to compare the in-hospital outcomes for patients treated with the FAST-PCI approach with outcomes for patients treated with the PPCI approach in a common system. The in-hospital data for 253 STEMI patients (March 2003-December 2009) treated with a FAST-PCI protocol were compared with 124 patients (January 2010-August 2011) treated with PPCI strategy alone. In-hospital mortality was the primary comparator. Stroke, major bleeding, and reinfarction during index hospitalization were also compared. The in-hospital mortality was significantly lower with FAST-PCI than with PPCI (2.77% vs 10.48%, p = 0.0017). Rates of stroke, reinfarction, and major bleeding were similar in the 2 groups. There was a lower frequency of pre-PCI Thrombolysis In Myocardial Infarction 0 flow (no patency) seen in patients treated with FAST-PCI compared with the PPCI patients (26.7% vs 62.7%, p <0.0001). Earlier infarct artery patency in the FAST-PCI group had a favorable impact on the incidence of cardiogenic shock on hospital arrival (3.1% vs 20.9%, p <0.0001). In conclusion, compared with a PPCI strategy in a common STEMI system of care, the FAST-PCI strategy was associated with earlier infarct artery patency and lower incidence of cardiogenic shock, as well as with reduced in-hospital mortality.

Economic methods in the century trial--a comprehensive lifestyle modification study for managing coronary artery disease.

While most studies assess the cost-effectiveness of treating acute coronary conditions, the Century Health Study for Cardiovascular Medicine (Century Trial) focuses on ameliorating coronary artery disease (CAD) through a comprehensive lifestyle modification program. This 1,300-patient phase III randomized study uses positron emission tomography for risk stratification, complemented with comprehensive educational and motivational therapy for patients with preclinical or established CAD. The Century Trial is in its second year of a five-year follow-up protocol, and it is one of the first to combine imaging technology and lifestyle modification as a way to improve patient behavior and health. In this article, we present the economic study design used in the Century Trial and provide considerable methodological detail to serve as reference for other researchers. We describe the cost and effect estimation methods as well as our analysis and uncertainty modeling plans. The study will incorporate quality-adjusted life years and use a societal perspective to measure both in-trial and lifetime costs through incremental cost-effectiveness ratios. The approach we follow should provide further evidence on the cost-effectiveness of comprehensive lifestyle modification programs in regressing coronary artery disease.

Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers.

OBJECTIVES: We sought to quantify ranges of normal myocardial perfusion and flow reserve in young, asymptomatic volunteers after systematic historical and laboratory screening for unexpected factors affecting coronary flow. BACKGROUND: Noninvasive cardiac positron emission tomography (PET) quantifies absolute flow and coronary flow reserve (CFR), thereby defining physiological severity of coronary artery disease for clinical studies or management. Defining "normal" coronary flow is a necessary prerequisite to its broad clinical application. METHODS: Volunteers aged 20 to 40 years of age without cardiac disease or other conditions underwent rest-dipyridamole stress cardiac PET with absolute quantitative flow measurements using Rb-82 in paired studies at least 7 days apart for reproducibility. The presence of coronary calcium, detectable blood nicotine or caffeine, dyslipidemia, and an extended family history of early clinical atherosclerosis were objectively and systematically examined for grouping subjects as true normal or not normal. RESULTS: We enrolled 125 volunteers, 107 (86%) underwent 2 PET scans. Fifty-six (45%) were classified as true normal, whereas 69 (55%) were classified as not normal. True normals had higher high-density lipoprotein and less PET scan heterogeneity. Hemodynamic responses to dipyridamole stress were similar. Rest flow was the same in both groups (0.72 ± 0.17 ml/min/g vs. 0.69 ± 0.14 ml/min/g, p = 0.164). However, stress flow (2.89 ± 0.50 ml/min/g vs. 2.63 ± 0.61 ml/min/g, p = 0.005) and CFR (4.17 ± 0.80 vs. 3.91 ± 0.86, p = 0.047) were higher in true normals. Paired studies were performed a median of 22 days (interquartile range: 15 to 39) apart. Reproducibility was improved in the true normal group. CONCLUSIONS: One-half of young, asymptomatic volunteers from the community harbor unexpected factors that mildly but systematically reduce stress flow, CFR, and reproducibility. This study establishes normal ranges and reproducibility for flow and CFR as the basis for clinical applications.

Partial volume correction incorporating Rb-82 positron range for quantitative myocardial perfusion PET based on systolic-diastolic activity ratios and phantom measurements.

BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18. CONCLUSION: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.

Prehospital 12-Lead Electrocardiogram within 60 Minutes Differentiates Proximal versus Nonproximal Left Anterior Descending Artery Myocardial Infarction.

INTRODUCTION: Acute anterior myocardial infarctions caused by proximal left anterior descending (LAD) artery occlusions are associated with a higher morbidity and mortality. Early identification of high-risk patients via the 12-lead electrocardiogram (ECG) could assist physicians and emergency response teams in providing early and aggressive care for patients with anterior ST-elevation myocardial infarctions (STEMI). Approximately 25% of US hospitals have primary percutaneous coronary intervention (PCI) capability for the treatment of acute myocardial infarctions. Given the paucity of hospitals capable of PCI, early identification of more severe myocardial infarction may prompt emergency medical service routing of these patients to PCI-capable hospitals. We sought to determine if the 12 lead ECG is capable of predicting proximal LAD artery occlusions. METHODS: In a retrospective, post-hoc analysis of the Pre-Hospital Administration of Thrombolytic Therapy with Urgent Culprit Artery Revascularization pilot trial, we compared the ECG findings of proximal and nonproximal LAD occlusions for patients who had undergone an ECG within 180 minutes of symptom onset. RESULTS: In this study, 72 patients had anterior STEMIs, with ECGs performed within 180 minutes of symptom onset. In patients who had undergone ECGs within 60 minutes (n = 35), the mean sum of ST elevation (STE) in leads V1 through V6 plus ST depression (STD) in leads II, III, and aVF was 19.2 mm for proximal LAD occlusions and 11.7 mm for nonproximal LAD occlusions (P = 0.007). A sum STE in V1 through V6 plus STD in II, III, and aVF of at least 17.5 mm had a sensitivity of 52.3%, specificity of 92.9%, positive predictive value of 91.7%, and negative predictive value of 56.5% for proximal LAD occlusions. When the ECG was performed more than 60 minutes after symptom onset (n = 37), there was no significant difference in ST-segment deviation between the 2 groups. CONCLUSION: The sum STE (V1-V6) and STD (II, III, aVF) on a 12-lead ECG can be used to predict proximal LAD occlusions if performed within the first hour of symptom onset. This should be considered a high-risk finding and may prompt prehospital direction of such patients to PCI-capable hospitals.

Pelvic ischemia is measurable and symptomatic in patients with coronary artery disease: a novel application of dynamic contrast-enhanced magnetic resonance imaging.

INTRODUCTION: Pelvic ischemia can manifest as vascular-mediated erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), and is associated with cardiac ischemia. AIMS: We aimed to develop a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique to measure pelvic perfusion in benign tissue. METHODS: Nine men with coronary artery disease (CAD) were compared with nine without. Images were acquired at 3T with T1-weighted DCE-MRI for perfusion. Two-compartment pharmacokinetic modeling was employed to fit signal enhancement from prostate, corpus cavernosal, and spongiosal tissues. MAIN OUTCOME MEASURES: Perfusion parameters and validated pelvic symptom scores were compared. RESULTS: The mean International Index of Erectile Function (IIEF) total score was worse in CAD (41.3 +/- 19.7) vs. controls (59.4 +/- 14.9, P = 0.04). The IIEF erectile function domain score trended to worse in CAD (13.7 +/- 9.7) vs. controls (22.0 +/- 9.9, P = 0.09). The mean total International Prostate Symptom Score (IPSS) trended to worse in CAD patients (13.2) than controls (7.0) (P = 0.10). Magnetic resonance perfusion analysis demonstrated lower mean maximal percent enhancement to P < 0.0001 in the CAD group vs. controls for all the following comparisons: prostate in CAD (22.4 +/- 0.4) vs. controls (26.3 +/- 0.1); cavernosal tissue in CAD (9.3 +/- 0.2) vs. controls (16.6 +/- 0.8); and spongiosal tissue in CAD (20.6 +/- 1.2) vs. controls (24.0 +/- 0.6). Comparison of mean wash-in rates in the unit of 10(-3)/second was also highly significant (P < 0.0001 for all tissues): prostate in CAD (574.0 +/- 18.0) was lower than controls (1,035.0 +/- 29.0); slower wash-in rates were seen in CAD cavernosal (58.0 +/- 4.0 vs. 139.0 +/- 9.0 in controls) and spongiosal tissue (134.0 +/- 6.0 vs. 278.0 +/- 12.0 in controls). CONCLUSION: These initial data demonstrate that pelvic perfusion can be measured in noncancerous tissues, and that perfusion correlates with validated measures of ED and LUTS.

Reducing radiation dose in rest-stress cardiac PET/CT by single poststress cine CT for attenuation correction: quantitative validation.

UNLABELLED: Cardiac PET/CT is optimized by cine CT with dedicated shift software for manual correction of attenuation-emission misregistration. Separate rest and stress CT scans incur greater radiation dose to patients than does standard helical PET/CT or "pure" PET using rotating rod attenuation sources. To reduce radiation dose, we tested quantitative accuracy of using a single poststress cine CT attenuation scan for reconstructing rest perfusion images to eliminate resting CT attenuation scans. METHODS: A total of 250 consecutive patients underwent diagnostic rest-dipyridamole myocardial perfusion PET/CT with (82)Rb and a 16-slice PET/CT scanner using averaged cine CT attenuation data during breathing at rest and stress. After correcting for any attenuation-emission misregistration, we quantitatively compared resting perfusion images reconstructed using rest cine CT attenuation data with the same resting emission data reconstructed with poststress cine CT attenuation data. Automated software quantifying average regional quadrant activity, severity, size, and combined size and severity of perfusion defects was used for this comparison. RESULTS: Resting perfusion images reconstructed using rest cine CT attenuation data were quantitatively comparable to resting images reconstructed with poststress cine CT attenuation data with no clinically significant differences. Twenty-five (10%) of 250 cases required shifting of stress cine CT attenuation data to achieve optimal attenuation-emission coregistration with resting perfusion data. Eliminating rest CT attenuation scans reduced CT radiation dose by 50% below rest-plus-stress cine CT protocols. CONCLUSION: Resting perfusion images reconstructed using poststress cine CT attenuation data are quantitatively comparable to resting images reconstructed with resting cine CT attenuation data. Eliminating the rest CT scan reduces CT radiation dose by 50%.

A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease.

BACKGROUND: In coronary artery disease (CAD), statins decrease morbidity and mortality but changes in myocardial perfusion abnormalities remain poorly defined. METHODS: We completed a randomized, double blind, placebo controlled, multi-center trial of 145 patients, 43 to 86 years old, with CAD from seven community and academic centers for cardiac positron emission tomography (PET) randomized to 6 months of atorvastatin 80 mg daily (72 patients) or placebo (73 patients). PET scans were obtained at baseline, 6 weeks and 6 months using N-13 ammonia or Rb-82 at rest and after dipyridamole or adenosine stress, submitted to the core PET laboratory in Houston. Change in stress induced perfusion defects from baseline to follow-up PET scans was scored by two independent, double blinded readers and by automated quantitative software. RESULTS: Total and LDL cholesterol decreased by 37% and 51%, respectively in atorvastatin but not placebo groups (P < .05). The primary endpoint, quantitative severity (lowest mean quadrant activity), showed no significant difference between treatment and placebo. The secondary endpoint, predefined blinded visual change scores, improved significantly after atorvastatin compared to placebo at six months (P = .02). Ad-hoc subgroup analysis showed interaction between quantitative defect size and treatment response with perfusion defects in the upper tertile of size by automated software improving more in atorvastatin than placebo groups (P = .016). CONCLUSION: The primary endpoint, quantitative severity of myocardial perfusion abnormalities by PET, did not improve after 6 months of atorvastatin 80 mg daily compared to placebo. The secondary endpoint of predefined blinded visual change scores significantly improved, as did a subgroup in the upper tertile of defect size, compared to placebo.