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.

Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness analysis from the BASKET-PROVE cohorts.

BACKGROUND: Clinical and cost-effectiveness of prasugrel vs. clopidogrel in acute coronary syndrome (ACS) was only evaluated using TRITON-TIMI 38 event rates. A comparative analysis of both drugs in contemporary European ACS patients is lacking. METHODS: To address this issue, cardiac and bleeding events of 2 "sister" multicenter stent trials, BASKET-PROVE (BP) I with clopidogrel and BPII with prasugrel (for 12months each) were used in a hybrid analysis. Medication costs were 2015 sales prices, event costs modelled for Denmark (DNK), Germany (GER) and Switzerland (SUI) and quality adjusted life years (QALY) by EQ-5D-3L questionnaire. RESULTS: In BPI and II, 1012 and 985 ACS-patients received drug eluting stents, respectively, followed-up for 2years. Compared to clopidogrel, prasugrel-treated patients had no more major cardiac events (5.2% vs. 6.4%, p=0.422) nor cardiac deaths (1.6% vs. 1.0%, p=0.255), but more major bleedings (4.0% vs. 1.7%, p<0.001) and altogether no difference in QALYs (-0.027 (95%CI: -0.064/0.011)). Prasugrel caused higher total expenditures per patient: 1116.3 (DNK), 1063.5 (GER) and 880.8 (SUI) EURO, respectively. Accordingly, incremental cost-effectiveness was negative for prasugrel vs. clopidogrel with ratios of -45,907 (DNK), -39,909 (GER) and -33,435 (SUI) EURO/QALY gained, making clopidogrel an economically dominant strategy, even after accounting for the non-randomized comparison. CONCLUSION: Findings of this contemporary European ACS-cohort showed markedly lower cardiac event rates than TRITON-TIMI 38 and no significant difference in 2-year QALYs between prasugrel and clopidogrel-treated patients. At current drug prices, clopidogrel use resulted in an economically dominant treatment strategy in Western European patients.

Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health-economic evaluation.

AIMS: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. METHODS/RESULTS: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. CONCLUSION: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.

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.

Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study.

AIMS: To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals. METHODS AND RESULTS: We followed 11,223 patients with no prior CVD having a first-time CAG in 1998-2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median). In recurrent event survival analysis, patients with SAP had 3-4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI) for patients with angiographically normal coronary arteries was 3.0(2.5-3.5), for angiographically diffuse non-obstructive CAD 3.9(3.3-4.6) and for 1-3-vessel disease 3.6-4.1(range)(all P<0.001). Mean accumulated hospitalization time was 3.5(3.0-4.0)(days/10 years follow-up) in reference individuals and 4.5(3.8-5.2)/7.0(5.4-8.6)/6.7(5.2-8.1)/6.1(5.2-7.4)/8.6(6.6-10.7) in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted). SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9-2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4-6.8) and for obstructive CAD 6.6-9.4(range)(all P<0.001). CONCLUSIONS: Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such patients does not ensure a benign cardiovascular prognosis.

No gender differences in prognosis and preventive treatment in patients with AMI without significant stenoses.

OBJECTIVE: To investigate possible gender differences in patients with acute myocardial infarction (AMI) and without significant stenoses on coronary angiography (CAG) regarding prognosis and use of secondary preventive medication. DESIGN: Nationwide register-based cohort study. PATIENTS: By compiling data from Danish registries, we identified 20,800 patients hospitalized with AMI during 2005-2007. We included the 834 women and 761 men without significant stenoses on CAG who were discharged and alive after 60 days. MAIN OUTCOME MEASURES: All-cause mortality, recurrent AMI, and redeeming a prescription for a lipid-lowering drug, beta-blocker, clopidogrel, or aspirin within 60 days of discharge. RESULTS: During follow-up, 97 women and 60 men died, resulting in a crude female/male hazard ratio (HR) of 1.51 (95% CI 1.09-2.08). After adjustment for age, time-period, and comorbidity, the gender difference was attenuated (HR 1.22, 95% CI 0.86-1.72). AMI recurrence was experienced by 28 women and 29 men with a female/male HR 0.88 (95% CI 0.52-1.48). After multivariable adjustment results were similar (HR 0.84, 95% CI 0.50-1.43). More women than men redeemed a prescription for lipid-lowering drugs with no differences in other medication. In the adjusted models lipid-lowering drugs, beta-blockers, clopidogrel, and aspirin were all redeemed equally with odds ratio (OR) 1.25 (95% CI 0.99-1.59), OR 1.10 (95% CI 0.88-1.37), OR 1.09 (95% CI 0.88-1.34), and OR 1.13 (95% CI 0.90-1.42), respectively. CONCLUSION: Our study shows that in a population of patients with a first admission for AMI and no significant stenoses on CAG, women share the same prospects as men regarding long-term prognosis and the extent of secondary preventive medical treatment.

[Establishment of a nurse-led heart failure clinic. Design and baseline data from the first two years]. / Etablering af en sygeplejerskebaseret hjertesvigtklinik. Design og baseline-data fra de første to år.

INTRODUCTION: Previous studies on the effect of heart failure clinics have shown a reduction in hospitalizations, reduced cost and improved quality of life. MATERIAL AND METHODS: We report on the establishment of a heart failure clinic and its impact on heart failure hospitalizations. Since September 1, 1999, a heart failure clinic has been operated at the Frederiksberg University Hospital. The clinic was designed with both a diagnostic and a therapeutic unit. The diagnostic unit offers open access to all patients with suspected heart failure, either through referral from general practitioners or from the medical departments of the hospital. In case of confirmed systolic heart failure, the patient is referred to the therapeutic unit. RESULTS: During the two years of operation, a total of 510 patients were registered in a newly established database (HJERTER+). Of these, 352 (69%) were found to have clinical evidence of heart failure, and 304 (86% of the heart failure patients) had left ventricular (LV) systolic dysfunction (ejection fraction < or = 0.45). Before referral, most patients with LV dysfunction had been treated with no or insufficient dose of ACE inhibitor (55%), and one third received beta-blockers (32%). During the two years of operation of the clinic, there was a 23% decline in heart failure related hospital admissions to the department of cardiology. DISCUSSION: Patients with systolic heart failure are not always optimally treated. The establishment of a heart failure clinic offering the combination of diagnosing and managing congestive heart failure appears to be effective both in terms of therapy optimization and with respect to a concomitant decline in hospitalization for heart failure.

An integrated approach to diagnosis and therapeutic management of patients with systolic heart failure in the Copenhagen metropolitan area.

BACKGROUND: Studies on the effect of heart failure clinics have been encouraging and convincing with respect to reduced hospitalizations, improved quality of life, and reduced cost. However, previous results have been derived from patient populations either recently discharged and with specific exclusion criteria or from heart transplant lists. We here report the establishment of a heart failure clinic that offers an integrated approach to both diagnosing and managing heart failure patients, the baseline characteristics of the first 283 patients treated, and the impact on heart failure hospitalizations during establishment. METHODS: Since September l, 1999, a heart failure clinic has been in operation at Frederiksberg University Hospital. The clinic was designed with both a diagnostic and a therapeutic unit. The diagnostic unit offers open access to all patients with suspected heart failure, either through referral from general practitioners or from the medical departments of the hospital. In the case of confirmed systolic heart failure, the patient is referred to the therapeutic unit for (1) uptitration and optimization of medical therapy and thorough information and education. In addition, the unit offers a rapid access track and the possibility of intravenous diuretic treatment. RESULTS: During the 21 months of operation, a total of 460 patients were referred to the clinic. Of these, 320 (70%) were found to have clinical evidence of heart failure, and 283 (88% of the patients with heart failure) had left ventricular systolic dysfunction (defined by an ejection fraction of < or =45%). These patients were seen in the clinic for education, control of fluid retention, and uptitration of medications. These patients with left ventricular dysfunction were predominantly elderly (aged 72.7 +/- 10.7 y) and most often male (73%). Ischemic heart disease was the most common etiology (55%). Before referral, most patients with left ventricular dysfunction had been treated with none or only low-dose angiotensin-converting enzyme inhibitor (55%), and fewer than one third received beta-blockers (29%). During the first year of operation of the clinic, there was a 23% decline of heart failure-related hospital admissions to the department of cardiology (from 396 to 306). CONCLUSIONS: Patients with systolic heart failure are not always optimally treated. The establishment of a heart failure clinic, which offers the combination of diagnosing and managing congestive heart failure, appears to be efficient both in terms of therapy optimization and with respect to a concomitant decline in hospitalization for heart failure.