Comparison of International Guidelines for Assessment of Suspected Stable Angina

OBJECTIVES This study sought to compare the performance of major guidelines for the assessment of stable chest pain including risk-based (American College of Cardiology/American Heart Association and European Society of Cardiology) and symptom-focused (National Institute for Health and Care Excellence) strategies. BACKGROUND Although noninvasive testing is not recommended in low-risk individuals with stable chest pain, guidelines recommend differing approaches to de ﬁ ning low-risk patients. METHODS Patient-level data were obtained from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test probability was determined and patients dichotomized into low-risk and intermediate-high – risk groups according to each guideline ’ s de ﬁ nitions. The primary endpoint was obstructive coronary artery disease on coronary computed tomography angiography. Secondary endpoints were coronary revascularization at 90 days and cardiovascular death or nonfatal myocardial infarction up to 3 years. RESULTS In total, 13,773 patients were included of whom 6,160 had coronary computed tomography angiography. The proportions of patients identi ﬁ ed as low risk by the American College of Cardiology/American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%, 19.8%, and 38.4% within SCOT-HEART. All guidelines identi ﬁ ed lower rates of obstructive coronary artery disease in low- versus intermediate-high – risk patients with a negative predictive value of $ 0.90. Compared with low-risk groups, all intermediate-high – risk groups had greater risks of coronary revascularization (odds ratio [OR]: 2.2

METHODS STUDY COHORTS. Patient-level data were obtained from the PROMISE and SCOT-HEART trial cohorts.
These are prospective multicenter randomized controlled trials investigating the utility of CCTA in the diagnosis and management of patients undergoing assessment of suspected stable angina due to CAD. The pragmatic designs (6,7) and principal findings (8,9) of these studies have been reported previously. The intervention arm in both studies consisted of CCTA, which was compared with usual care. Details of cohort-specific inclusion and exclusion criteria have been previously described (10). To confirm guideline utility in distinct clinical settings and across populations, the study cohorts were analyzed separately.

GUIDELINE-DETERMINED DIAGNOSTIC GROUPS.
For the ACC/AHA and ESC guideline analysis, PTP of CAD was determined according to the DF-CASS and CADC risk models, respectively. Diagnostic risk groups (low, intermediate, high) were then defined as specified in each guideline (Online Table 1   by study cohort and according to intention-to-treat, irrespective of compliance with scanning. The diagnostic and revascularization endpoints were analyzed using chi-squared tests and log-binomial regression (11,12), with results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) and p values. Clinical events were analyzed with Cox regression and reported as hazard ratios (HRs) with cumulative incidence plots constructed. Additional performance measures were determined including discrimination, sensitivity, specificity, positive predictive value, and negative predictive value. In PROMISE, these performance measures were assessed 1 year post-randomization using the method of Heagerty et al. (13) to account for those lost to follow-up in the trial. In addition to these stratumspecific analyses, we modeled interaction terms for allocation and within study cohort to provide hypothesis testing for interaction on the relative scale.
Comparison of diagnostic metrics including predictive values between the overlapping groups of patients determined to be low risk by each of the 3 guidelines were made using previously described methods (14)(15)(16)(17). Net reclassification improvement was compared between the NICE guideline and both ACC/AHA and ESC guidelines (18). All primary and secondary endpoints are reported unadjusted. Data are presented as mean AE SD or mean differences with 95% CI. Statistical significance was taken as 2-sided p < 0.05.     Table 4). In both trial cohorts, identification as low risk was associated with a negative predictive value for coronary revascularization of >0.97 for each of the 3 guidelines that was the same irrespective of guideline adopted (p > 0.05 for all).

RESULTS
In contrast, the positive predictive value for coronary revascularization of the NICE classification was greater than either of the other guidelines (p < 0.001 for all).    (8,9,22).
In practice however, it is well appreciated that many patients undergoing assessment for possible stable angina are at low risk of both underlying CAD and future ischemic events, at least in the short to medium term. In the primary care setting, <10% of such patients are ultimately identified as having a coronary cause for their symptoms (23). Recognizing this, substantial work has been done to update, refine, and extend risk models for estimating the PTP CAD, albeit often in highly selected populations referred for invasive angiography (24)(25)(26)(27)(28)  Values are n or n (%). *Prognostically significant CAD was defined as 3-vessel disease, 2-vessel disease including the proximal left anterior descending artery, or obstructive disease involving the left main stem.
CABG ¼ coronary artery bypass graft; CAD ¼ coronary artery disease; CCTA ¼ coronary computed tomography angiography; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; other abbreviations as in Table 1.   Tables 1 and 3.  the diagnosis of CAD, these principally relate to suboptimal specificity and a tendency to overestimate stenosis severity. In contrast, the very high diagnostic sensitivity offered by CCTA provides necessary reassurance regarding the ability of all strategies to exclude significant CAD. Importantly, the disease prevalence identified is unlikely to be an underestimate, and in fact the rates of CAD may be lower than we have reported in both the low-and high-risk diagnostic groups.  TRANSLATIONAL OUTLOOK 2: The clinical outcomes arising from international guidelines should be robustly evaluated to ensure they achieve optimal safety and efficacy.