BACKGROUND Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.)

Background Abnormal acid gastroesophageal reflux is common in idiopathic pulmonary fibrosis and is considered a risk factor for its development. Retrospective studies have suggested improved outcomes in patients treated with anti-acid therapy. The aim of this study was to determine the association between anti-acid therapy and disease progression in idiopathic pulmonary fibrosis. Methods Patients with IPF were identified from the placebo arms of the three IPFnet randomized clinical trials. Case report forms were designed to prospectively capture data regarding gastroesophageal reflux diagnosis and treatment. These data were analyzed to determine the relationship between use of anti-acid therapy (i.e. proton pump inhibitors and histamine-2 blockers) and change in forced vital capacity using a longitudinal repeated-measures model. Secondary outcomes analyzed included acute exacerbation, all-cause hospitalization, and all-cause mortality. Findings Two hundred and forty-two patients with idiopathic pulmonary fibrosis were randomized to receive placebo therapy. Fifty-one percent were taking anti-acid therapy upon enrollment. There were no significant differences in demographics and pulmonary physiology between patients taking and not taking anti-acid therapy. After adjustment for sex, baseline forced vital capacity %predicted, and baseline diffusing capacity for carbon monoxide %predicted, patients taking anti-acid therapy at baseline had a slower decline in forced vital capacity (estimated change over 30-weeks of -0.06 liters vs. -0.12 liters, p-value = 0.05). Patients taking anti-acid therapy at baseline had fewer acute exacerbations (no events versus nine events, p-value <0.01) during the study period. Interpretation The use of anti-acid therapy was associated with a slower decline in forced vital capacity over time and fewer acute exacerbations in patients with idiopathic pulmonary fibrosis. These findings support the hypothesis that abnormal acid gastroesophageal reflux contributes to disease progression and suggest that anti-acid therapy may be beneficial in patients with idiopathic pulmonary fibrosis.

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure.MethodsThree investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria.ResultsThirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality.ConclusionsIn this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures.

Background: Idiopathic pulmonary fi brosis (IPF) is a progressive lung disease with pulmonary vasculopathy. Objective: The purpose of this study was to determine whether sildenafi l improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction. Methods: The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafi l on 6MWD in patients with advanced IPF, defi ned by carbon monoxide diffusing capacity , 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafi l treatment, and changes in 6MWD, St. George's Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks. Results: The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafi l experienced less decrement in 6MWD (99.3 m; P 5 .01) and greater improvement in SGRQ (13.4 points; P 5 .005) and EuroQol visual analog scores (17.9 points; P 5 .04) than subjects receiving placebo. In the subgroup with RVH, sildenafi l was not associated with change in 6MWD ( P 5 .13), but was associated with greater relative improvement in SGRQ (14.8 points; P 5 .02) vs subjects receiving placebo. Sildenafi l treatment in those with RVSD and RVH was not associated with change in SF-36. Conclusions: Sildenafi l treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafi l also improves quality of life in subjects with RVH and RVSD.CHEST 2013; 143(6):1699-1708Abbreviations: 6MWD 5 6-min walk distance; BNP 5 brain natriuretic peptide; D lco 5 carbon monoxide diffusing capacity; IPF 5 idiopathic pulmonary fi brosis; PAH 5 pulmonary arterial hypertension; PH 5 pulmonary hypertension; QOL 5 quality of life; RHC 5 right-sided heart catheterization; RV 5 right ventricular; RVH 5 right-sided ventricular hypertrophy; RVSD 5 right-sided ventricular systolic dysfunction; RVSP 5 right-sided ventricular systolic pressure;

Objective Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. Methods A total of 221 participants with pediatric SLE (ages 10–21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n = 113) or placebo (n = 108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. Results Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P = 0.24). The atorvastatin group achieved lower hsCRP (P = 0.04), total cholesterol (P < 0.001), and low-density lipoprotein (P < 0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023–0.0144 mm/year; P < 0.05). Serious adverse events and critical safety measures did not differ between groups. Conclusion Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.