Prediction models as gatekeepers for diagnostic testing in angina patients with suspected chronic coronary syndrome.

AIMS: Assessment of pre-test probability (PTP) is an important gatekeeper when selecting patients for diagnostic testing for coronary artery disease (CAD). The 2019 European Society of Cardiology (ESC) guidelines recommend upgrading PTP based on clinical risk factors but provide no estimates of how these affect PTP. We aimed to validate two published PTP models in a contemporary low-CAD-prevalence cohort and compare with the ESC 2019 PTP. METHODS AND RESULTS: Previously published basic and clinical prediction models and the ESC 2019 PTP were validated in 42 328 patients (54% women) ≥30 years old without previous CAD referred for cardiac computed tomography angiography in a region of Denmark from 2008 to 2017. Obstructive CAD prevalence was 8.8%. The ESC 2019 PTP and basic model included angina symptoms, sex, and age, while the clinical model added diabetes mellitus family history of CAD, and dyslipidaemia. Discrimination was good for all three models [area under the receiver operating curve (AUC) 0.76, 95% confidence interval (CI) (0.75-0.77), 0.74 (0.73-0.75), and 0.76 (0.75-0.76), respectively]. Using the clinically relevant low predicted probability ≤5% of CAD cut-off, the clinical and basic models were well calibrated, whereas the ESC 2019 PTP overestimated CAD prevalence. At a cut-off of ≤5%, the clinical model ruled out 36.2% more patients than the ESC 2019 PTP, n = 23 592 (55.7%) vs. n = 8 245 (19.5%), while missing 824 (22.2%) vs. 132 (3.6%) cases of obstructive CAD. CONCLUSION: A prediction model for CAD including cardiovascular risk factors was successfully validated. Implementation of this model would reduce the need for diagnostic testing and serve as gatekeeper if accepting a watchful waiting strategy for one-fifth of the patients.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Do ultrathin strut bare-metal stents with passive coating improve efficacy in large coronary arteries? Insights from the randomized, multicenter BASKET-PROVE trials.

BACKGROUND: The new generation thinner-strut silicon carbide (SiC) coated cobalt chromium (CoCr) bare-metal stents (BMS) are designed to accelerate rapid endothelialisation and reduce thrombogenicity when implanted in coronary arteries. However, smaller studies suggest higher rates of symptomatic restenosis in patients receiving the newer generation BMS. We investigated the efficacy of a newer generation ultrathin strut silicon-carbide coated cobalt-chromium (CoCr) BMS (SCC-BMS) as compared to an older thin-strut uncoated CoCr BMS (UC-BMS) in patients presenting with coronary artery disease requiring stenting of large vessels (≥3.0 mm). METHODS: All patients randomized to SCC- (n = 761) or UC-BMS (n = 765) in the two BASKET-PROVE trials were included. Design, patients, interventions and follow-up were similar between trials except differing regimens of dual antiplatelet therapy. The primary endpoint was clinically driven target-vessel revascularization within 24 months. Safety endpoints of cardiac death, non-fatal myocardial infarction (MI), and definite/probable stent thrombosis (ST) were also assessed. We used inverse probability weighted proportional hazards Cox regressions adjusting for known confounders. RESULTS: Demographics, clinical presentation, and risk factors were comparable between the groups, but patients receiving SCC-BMS underwent less complex procedures. The risk for clinically driven TVR was increased om the SCC-BMS group compared to the UC-BMS group (cumulative incidence, 10.6% vs. 8.4%; adjusted relative hazard [HR], 1.49 [95% CI, 1.05-2.10]). No differences in safety endpoints were detected, cardiac death (1.6% vs. 2.8%; HR, 0.62 [CI, 0.30-1.27]), non-fatal MI (3.2% vs. 2.5%; HR, 1.56 [CI, 0.83-2.91]), and definite/probable ST (0.8% vs. 1.1%; HR, 1.17 [CI, 0.39-3.50]). Differences in strut thickness between the two stents did not explain the association between stent type and clinically driven TVR. CONCLUSIONS: In patients requiring stenting of large coronary arteries, use of the newer generation SCC-BMS was associated with a higher risk of clinically driven repeat revascularization compared to the UC-BMS with no signs of an offsetting safety benefit.

Drug-eluting stents in large coronary vessels improve both safety and efficacy compared with bare-metal stents in women: a pooled analysis of the BASKET-PROVE I and II trials.

Background: Drug-eluting stents (DES) have proven superior to bare-metal stents (BMS) in terms of safety and efficacy. However, inference to the female subgroup has been limited by low enrolment rates of women in clinical trials. The objective of this study was to investigate the safety and efficacy of DES versus BMS in women and men. Methods: In a pooled analysis of two all-comers randomised trials (Basel Stent Kosten-Effektivitäts Trial-Prospective Validation Examination (BASKET-PROVE) and BASKET-PROVE II) (n=4605), we examined safety and efficacy of DES versus BMS according to sex. Patients were followed 2 years for a composite endpoint of cardiac death, non-fatal myocardial infarction (MI) and clinically driven target-vessel revascularisation not related to MI. Results: Among the 1076 women and 3529 men included in the analysis, 65.6% of the women and 67.2% of the men were randomised to receive DES. At baseline, men had more complex coronary artery disease than women. After 2 years, DES reduced rates of major adverse cardiac events (MACE) compared with BMS in both women (cumulative incidence, 6.1% vs 14.7%; adjusted HR 0.36 (95% CI 0.24 to 0.54)) and men (7.7 vs 12.1%, HR 0.62 (0.50 to 0.77)), although the reduction in MACE rates was more pronounced in women (adjusted p=0.02 for sex-stent interaction). Event rates were lower in DES for both safety and efficacy outcomes, with the largest effect seen for non-MI TVR, in both women (2.3 vs 9.2%, adjusted HR 0.24 (0.13 to 0.44)) and men (4.0 vs 7.8%, adjusted HR 0.48 (0.36 to 0.64)) (adjusted p=0.049 for sex-stent interaction). Conclusions: In patients requiring stenting of large coronary arteries, DES were associated with improved safety in women and superior efficacy in both sexes as compared with BMS.

Use of diagnostic coronary angiography in women and men presenting with acute myocardial infarction: a matched cohort study.

BACKGROUND: Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men. METHODS: The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA. RESULTS: Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67-1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA. CONCLUSION: In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for the sex-related differences in the use of DCA. Importantly,clinical justification for opting out an invasive strategy was not documented in almost one fifth of patients not receiving a DCA.