复旦大学：《循证医学》课程教学资源（参考教材）Unit 03 疾病诊断证据的分析与评价

CORONARY CT ANGIOGRAPHY FOR ACUTE CHEST PAIN charged from the emerg ncy depa ment (47 vs 12%of patients in the standard. pcoool.witfeweradmisionsonobo tion unit. CCTA Prespe cal adverse events were nfre 86 6.7h jor adverse cardiovascular events during the 28- day follow-up:six after standard evaluation in the emergency department (four myocardial in- 6 1218240364248 two cases of unstable angina pec Length ofStay (hr) of P mvocardial infarction and one case of unstable angina pectoris for which percutaneous coronary intervention was required)(P=0.18).In both of the latter patients,CCTA established clinically sig Length of Stay in the Hospital and Proporion of Patients tive fregu cy of dischar e from the index visit according to th ress tests ted me ngth of stay is shown.The hori ngth c CCTA the CCTA group vs.2 rdio. .thestandard-evaigroP01) thoracic surgery for an identified anomalous coro nary artery and a transient increase in the creati nine level after CCTA without the need for dialysis in a patient wit a urethra stone and hydrone vith adi RESOURCE UTILIZATION AND RADIATION EXPOSURE (12.3t5mSv. Table 3 shows resource utilization.Overall,more Detailed cost data were available in a subgroup diagnostic testing was performed in the CCTA of all 649 patients from five centers (Table 3 e standard-evaluation group The mean costs of care from the initial visit i the emergency dep ent throug n the 28 nd the the the CCTA group than among patients in the stan- dard-evaluation group,but the differences were DISCUSSION not significant(P=0.06 and P=0.16,respectively) (Table 3). strat Nearly all patients in the CC T This to a ,1 oup(484 of egy-contro ed to stand sation str received radiation exposure from an imaging test emergency department with chest pain sugges- or procedure.Hence,cumulative radiation expo-tive of an acute coronary syndrome,safely im- sure was significantly higher in the CCTA group proves the efficiency of clinical decision making (Table 3).The mean radiation exposure fron as compared with a standard eva ation in the CCTA was 11.3+5.3 mSv and was lower than that emergency department.The cumulative costs of N ENGLJ MED 367:4 NEJM.ORG JULY 26,2012 305

coronary CT Angiogr aphy for Acute Chest Pain n engl j med 367;4 nejm.org july 26, 2012 305 charged from the emergency department (47%, vs. 12% of patients in the standard-evaluation group; P<0.001), with fewer admissions to an observa￾tion unit. Safety End Points Prespecified clinical adverse events were infre￾quent in this trial (Table 2). No cases of undetect￾ed acute coronary syndromes were identified in either study group. Overall, there were eight ma￾jor adverse cardiovascular events during the 28- day follow-up: six after standard evaluation in the emergency department (four myocardial in￾farctions and two cases of unstable angina pec￾toris for which percutaneous coronary interven￾tion was required) and two after CCTA (one myocardial infarction and one case of unstable angina pectoris for which percutaneous coronary intervention was required) (P=0.18). In both of the latter patients, CCTA established clinically sig￾nificant coronary artery disease during the index hospitalization, but both patients had negative stress tests and were initially treated medically. Two periprocedural complications occurred in the CCTA group (perioperative bleeding after cardio￾thoracic surgery for an identified anomalous coro￾nary artery and a transient increase in the creati￾nine level after CCTA without the need for dialysis in a patient with a urethral stone and hydrone￾phrosis), and no periprocedural complications occurred in the standard-evaluation group. Resource Utilization and Radiation Exposure Table 3 shows resource utilization. Overall, more diagnostic testing was performed in the CCTA group than in the standard-evaluation group (P<0.001). Both the cumulative rate of invasive coronary angiography during the index hospital￾ization and follow-up and the rate of coronary revascularization were higher among patients in the CCTA group than among patients in the stan￾dard-evaluation group, but the differences were not significant (P=0.06 and P=0.16, respectively) (Table 3). Nearly all patients in the CCTA group (484 of 501 patients; 97%), but only 167 of 499 patients randomly assigned to standard evaluation (33%) received radiation exposure from an imaging test or procedure. Hence, cumulative radiation expo￾sure was significantly higher in the CCTA group (Table 3). The mean radiation exposure from CCTA was 11.3±5.3 mSv and was lower than that from single-photon-emission CT (14.1±4.8 mSv, P<0.001). The 78 patients who underwent CCTA with the use of an advanced 128-slice, dual￾source CT scanner had lower radiation exposure (6.2±3.8 mSv) than did the remaining patients (12.3±5 mSv). Detailed cost data were available in a subgroup of all 649 patients from five centers (Table 3). The mean costs of care from the initial visit in the emergency department through the 28-day follow-up were similar in the CCTA group and the group that received standard evaluation in the emergency department (P=0.65). Discussion This prospective, multicenter, randomized, strat￾egy-controlled trial was designed primarily to as￾sess whether CCTA, incorporated early into an evaluation strategy for patients presenting to an emergency department with chest pain sugges￾tive of an acute coronary syndrome, safely im￾proves the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department. The cumulative costs of Proportion of Patients Discharged (%) 100 80 90 70 60 40 30 10 50 20 0 0 6 12 18 24 30 36 42 48 Length of Stay (hr) No. of Patients in Emergency Department or Hospital CCTA Standard evaluation 501 499 404 484 174 387 191 403 159 331 95 135 66 72 70 77 57 63 CCTA Standard evaluation in emergency department 8.6 hr 26.7 hr Figure 2. Length of Stay in the Hospital and Proportion of Patients Discharged. The cumulative frequency of discharge from the index visit according to the length of stay is shown. The horizontal line indicates the median length of stay in the two study groups, which was significantly different (8.6 hours in the CCTA group vs. 26.7 hours in the standard-evaluation group, P<0.001)

The NEW ENGLAND JOURNAL f MEDICINE Table 3.Resource Utilization,Radiation Exposure,and Costs of Care. Variable Index Visit Index Plus Follow-up Visit S06 Standard P Valu iagnostic testing-no.of patients( 0.00 No testing Functional testing-no.( 0.001 0.00 SPECT vecoronary angiography-no.(%) 0c1 17 86 Cumulative radiation -mSv/patient 1390 143109 0001 000 ency depar men 2,101±1,0702,566±1,323 Median tile range 1,435-2,161 Hos 0.19 1,9256,6971,30345,333 0.75 0.65 4,026±6,7923,8745,298 4,289±7,10406045,452 Median 9 2,742 1,946 2809 Interquartile range 1,504-4,0571,755-3,832 1,5144,1641,822-4,060 Serial measu t of biomarkers and fro CTA, sedischarged from an observation unit. eests interventions,and radiation ex-increased diagnostic testing in the CCrA The average lengt and rad posure ital the Phe CCTA as the time to diagnosis.Further. syndromes.There were no undetected cases of gency department were higher with CCTA than acute coronary syndromes in either study group with a standard evaluation in the partment.Ines resuits were d not res any m diagnoses.More m and with ved aluatonentt n group th group N ENGLJ MED 367:4 NEJM.ORG JULY 26,2012

T h e n e w e ngl a nd j o u r na l o f m e dic i n e 306 n engl j med 367;4 nejm.org july 26, 2012 diagnostic tests, interventions, and radiation ex￾posure were also evaluated. The average length of stay in the hospital, the primary end point of the trial, was significantly reduced in the CCTA group, as was the time to diagnosis. Further￾more, rates of direct discharge from the emer￾gency department were higher with CCTA than with a standard evaluation in the emergency de￾partment. These results were achieved without putting patients at greater risk for undetected acute coronary syndromes and without an in￾crease in the cost of care. However, we observed increased diagnostic testing in the CCTA group and increased radiation exposure. An important consideration when results show more efficient triage is whether that gain is achieved at the risk of undetected acute coronary syndromes. There were no undetected cases of acute coronary syndromes in either study group, suggesting that the earlier and greater number of discharges in the CCTA group did not result in any missed diagnoses. More major adverse cardio￾vascular events were observed in the standard￾evaluation group than in the CCTA group, Table 3. Resource Utilization, Radiation Exposure, and Costs of Care.* Variable Index Visit Index Plus Follow-up Visit CCTA (N=501) Standard Evaluation (N=499) P Value CCTA (N=501) Standard Evaluation (N=499) P Value Diagnostic testing — no. of patients (%)† <0.001 <0.001 No testing‡ 9 (2) 109 (22) 9 (2) 89 (18) 1 test 376 (75) 337 (68) 359 (72) 350 (70) ≥2 tests 116 (23) 53 (11) 133 (27) 60 (12) Functional testing — no. (%)§ <0.001 <0.001 SPECT 50 (10) 124 (25) 58 (12) 133 (27) Stress echocardiography 20 (4) 102 (20) 20 (4) 102 (20) ETT 12 (2) 147 (29) 22 (4) 162 (32) Invasive coronary angiography — no. (%) 54 (11) 36 (7) 0.06 59 (12) 40 (8) 0.06 Intervention — no. (%) PCI 24 (5) 14 (3) 0.14 27 (5) 17 (3) 0.16 CABG 5 (1) 4 (1) 0.99 5 (1) 4 (1) 0.99 Cumulative radiation exposure — mSv/patient¶ 13.9±10.4 4.7±8.4 <0.001 14.3±10.9 5.3±9.6 <0.001 Costs of care — U.S. dollars‖ <0.001 Emergency department Mean 2,101±1,070 2,566±1,323 Median 1,770 2,293 Interquartile range 1,435–2,161 1,592–3,583 Hospital 0.19 Mean 1,925±6,697 1,308±5,333 Total 0.75 0.65 Mean 4,026±6,792 3,874±5,298 4,289±7,110 4,060±5,452 Median 1,937 2,742 1,946 2,809 Interquartile range 1,504–4,057 1,755–3,832 1,514–4,164 1,822–4,060 * Plus–minus values are means ±SD. Percentages may not sum to 100 because of rounding. CABG denotes coronary-artery bypass grafting, ETT exercise treadmill testing, PCI percutaneous coronary intervention, and SPECT single-photon-emission computed tomography. † Diagnostic testing included CCTA, ETT, SPECT, stress echocardiography, and invasive coronary angiography. ‡ Serial measurement of biomarkers and electrocardiographic testing were not considered as diagnostic tests in this table. § At the index visit, functional testing was the second test in the CCTA group and the first test in the standard-evaluation group. ¶Radiation exposure included exposure from CCTA, SPECT, and invasive coronary angiography. ‖ Costs included those for patients discharged directly from the emergency department and those discharged from an observation unit

CORONARY CT ANGIOGRAPHY FOR ACUTE CHEST PAIN though the study did not have the statistical are not as accessible.Similarly,the results cannot owe r to neralized to clinical sites that p Tooppothcsnbeocedeaaeedagocpgoon"h a CCTA-based evaluation. standard evaluation. The prevalence of acute coronary syndromes in Inherent in the design of any randomized comparativ rial as ng a testing proce is th interven hias in eho me in the CCTA group.For both g uns of natients for acute coronary syndromes (observed rate of number of clinicians at the nine sites who were acute coronary syndromes,7.5%,vs.2 and 4% not directly associated with the study and whose previous studies ,a greater numb decis er provide high same sid and nary arte disease the resuts of this study may not be applicable to may influence clinical decision making toward invasive angiography.This concept is consistent with recent data suggesting that in a Medicare older than 74 years of age. coron A in a nonen 0e com ite coronary syn ed wirh ngeaCCTA in this trial no decrease in total costs for the improved the efficieney ofelinical decision mal index visit and during 28-day follow-up was ob- ing for triage in the emergency department.with served in a subgroup of 649 patients from five of a shorter length of stay in the hospital and more nine ealodarenotaa direct discharges from the emergency department improvement appe ts in determ s at great 4 isits to the em ased diagnostic resting and higher radiation izations over a longer time course exposure in the CCTA group,with no overall Cumulative radiation exposure was higher in reduction in the cost of care.These data should allow providers and patients to make informec evaluation group.Recent data show that decisions about the use of this technology as an ity CCT nts:thise could use lower doses of radiation Lowe dose radiation should be considered in efforts to Lang.and apply this strategy more widely,as well as in alth (UL1RR025758.K23HL098370.and particular groups of patients reports r There L e on Dr.I However the results of triage decision making and particularly the timing of decisions to dis charge or hospitalize patients would probably be N ENGLJ MED 367:4 NEJM.ORG JULY 26,2012 307

coronary CT Angiogr aphy for Acute Chest Pain n engl j med 367;4 nejm.org july 26, 2012 307 though the study did not have the statistical power to support the conclusion that major ad￾verse cardiovascular events may be reduced after a CCTA-based evaluation. The prevalence of acute coronary syndromes in a patient population is an important determinant of the risk–benefit ratio, given that CCTA is an advanced diagnostic imaging test that entails the administration of iodinated contrast material, ra￾diation exposure, and costs. In our study popu￾lation of patients who were at intermediate risk for acute coronary syndromes (observed rate of acute coronary syndromes, 7.5%, vs. 2 and 4% in previous studies10,11), a greater number of invasive coronary procedures were performed after CCTA than after a standard evaluation. Information on the presence of anatomical coronary artery disease may influence clinical decision making toward invasive angiography. This concept is consistent with recent data suggesting that in a Medicare population, imaging of the coronary anatomy with CCTA in a nonemergency setting led to greater use of downstream testing and procedures, as com￾pared with functional stress testing.12 In this trial, no decrease in total costs for the index visit and during 28-day follow-up was ob￾served in a subgroup of 649 patients from five of nine sites in which complete billing data were available. Long-term outcome data are not avail￾able; such data might have allowed a determina￾tion of whether CCTA results in fewer repeat visits to the emergency department and hospital￾izations over a longer time course. Cumulative radiation exposure was higher in the group randomly assigned to CCTA than in the standard-evaluation group. Recent data show that diagnostic-quality CCTA imaging can be per￾formed with exposure of less than 5 mSv in se￾lected patients; this suggests that future studies could use lower doses of radiation.16,17 Lower￾dose radiation should be considered in efforts to apply this strategy more widely, as well as in particular groups of patients. There are several limitations of the present study and analysis. Enrollment occurred only dur￾ing weekday hours when all imaging testing was available with technologists and readers on site. However, the results of triage decision making and particularly the timing of decisions to dis￾charge or hospitalize patients would probably be different if the imaging studies were carried out during the night, when testing and interpretation are not as accessible. Similarly, the results cannot be generalized to clinical sites that perform a dedicated accelerated diagnostic protocol18 in the standard evaluation. Inherent in the design of any randomized, comparative-effectiveness trial assessing a testing procedure is the lack of blinding to the interven￾tion. We acknowledge that there may have been a bias in decision making toward earlier discharge in the CCTA group. For both groups of patients, however, the decision making was left to a large number of clinicians at the nine sites who were not directly associated with the study and whose decisions were subject to the same imperatives to provide high-quality clinical care and to take into account medical and legal considerations. Finally, the results of this study may not be applicable to populations that we did not study, including pa￾tients younger than 40 years of age and those older than 74 years of age. In conclusion, in this trial involving patients with suspected acute coronary syndromes, an evaluation strategy incorporating early CCTA, as compared with a standard evaluation strategy, improved the efficiency of clinical decision mak￾ing for triage in the emergency department, with a shorter length of stay in the hospital and more direct discharges from the emergency department. This improvement appeared to be accomplished safely, without putting patients at greater risk for undetected acute coronary syndromes. There was increased diagnostic testing and higher radiation exposure in the CCTA group, with no overall reduction in the cost of care. These data should allow providers and patients to make informed decisions about the use of this technology as an option for evaluation when symptoms are sugges￾tive of an acute coronary syndrome. Supported by grants from the National Heart, Lung, and Blood Institute (U01HL092040 and U01HL092022) and the Na￾tional Institutes of Health (UL1RR025758, K23HL098370, and L30HL093896, to Dr. Truong). Dr. Gazelle reports receiving consulting fees from GE Health￾care; Dr. Hauser, receiving consulting fees from Astellas and the Harvard Clinical Research Institute; Dr. Hoffmann, receiving grant support from the American College of Radiology Imaging Network, Bracco Diagnostics, Genentech, and Siemens Health￾care on behalf of his institution; Dr. Nagurney, receiving grant support from Alere (Biosite), Brahms Diagnostica (Fischer), and Nanosphere on behalf of his institution; Dr. Truong, receiving grant support from St. Jude Medical and Qi Imaging on behalf of her institution and travel support from Medconvent and the So￾ciety of Cardiac Computed Tomography; Dr. Wiviott, receiving consulting fees from Arena Pharmaceuticals, AstraZeneca, Bayer, Bristol-Myers Squibb, and Ortho-McNeil, grant support from