Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Digging into Linked Parliamentary Data (DiLiPaD)

The goals of the DiLiPaD project were to 1) enhance the existing corpora of parliamentary data from the UK (1803 to the present) and Canada (1867 to the present) to the same standards as the comparable Netherlands corpus covering 1814 to the present; 2) develop new tools for the study of this data; 3) explore research questions, both in conjunction with and following on from the enhancement of the data and the provision of these tools. Specifically the project team investigated gender and politics, focusing on the role of women in parliamentary debate, the framing of same-sex marriage and the measuring of emotion in parliamentary debates

The impact of processes of care on myocardial infarct size in patients with ST-segment elevation myocardial infarction: Observations from the CRISPAMI trial

Background: Primary percutaneous coronary intervention (PCI) is the most common method of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) in the United States. The intersection between processes of care and performance measures such as door-to-balloon (D2B) times and clinical trials evaluating novel therapies for STEMI has not been fully investigated. Hypothesis: Processes of STEMI care, incorporating clinical trial enrollment and randomization, in patients undergoing reperfusion with primary PCI in the Counterpulsation Reduces Infarct Size Pre-Percutaneous Coronary Intervention Acute Myocardial Infarction trial (CRISP-AMI) will conform to current standards of care. Methods: Patients enrolled in CRISP-AMI were included in the current analysis. Processes of care during reperfusion were recorded prospectively and compared between groups. Results: A total of 337 patients with anterior STEMI without cardiogenic shock were randomized in CRISP-AMI. Complete processes-of-care data were available for 303 patients (89.9%). In this cohort, 68.0% of patients underwent reperfusion within 90 minutes of hospital contact, and the median D2B time was 71 minutes. Time from hospital contact to informed consent was significantly different across different regions (North America, 45 minutes; India, 35 minutes; Europe, 20 minutes). Conclusions: In CRISP-AMI, reperfusion was accomplished in a timely fashion while incorporating informed consent and randomization among patients with anterior myocardial infarction. Further study of patients' comprehension and preferences during the informed-consent process in STEMI patients is warranted so that innovative drugs and devices can be safely and ethically tested

Fractional Flow Reserve versus Angiography–Guided Management of Coronary Artery Disease: A Meta–Analysis of Contemporary Randomised Controlled Trials

Background and Aims: Randomised controlled trials (RCTs) comparing outcomes after fractional flow reserve (FFR)-guided versus angiography-guided management for obstructive coronary artery disease (CAD) have produced conflicting results. We investigated the efficacy and safety of an FFR-guided versus angiography-guided management strategy among patients with obstructive CAD. Methods: A systematic electronic search of the major databases was performed from inception to September 2022. We included studies of patients presenting with angina or myocardial infarction (MI), managed with medications, percutaneous coronary intervention, or bypass graft surgery. A meta-analysis was performed by pooling the risk ratio (RR) using a random-effects model. The endpoints of interest were all-cause mortality, MI and unplanned revascularisation. Results: Eight RCTs, with outcome data from 5077 patients, were included. The weighted mean follow up was 22 months. When FFR-guided management was compared to angiography-guided management, there was no difference in all-cause mortality [3.5% vs. 3.7%, RR: 0.99 (95% confidence interval (CI) 0.62–1.60), p = 0.98, heterogeneity (I2) 43%], MI [5.3% vs. 5.9%, RR: 0.93 (95%CI 0.66–1.32), p = 0.69, I2 42%], or unplanned revascularisation [7.4% vs. 7.9%, RR: 0.92 (95%CI 0.76–1.11), p = 0.37, I2 0%]. However, the number patients undergoing planned revascularisation by either stent or surgery was significantly lower with an FFR-guided strategy [weighted mean difference: 14 (95% CI 3 to 25)%, p =< 0.001]. Conclusion: In patients with obstructive CAD, an FFR-guided management strategy did not impact on all-cause mortality, MI and unplanned revascularisation, when compared to an angiography-guided management strategy, but led to up to a quarter less patients needing revascularisation

Revascularisation or medical therapy in elderly patients with acute anginal syndromes (RINCAL) a randomised trial

Aims: To determine whether an intervention-guided strategy is superior to optimal medical therapy (OMT) for treating non-ST-elevation myocardial infarction (NSTEMI) in the elderly. Methods and results: Patients (≥80 years, chest pain, ischaemic ECG, and elevated troponin) were randomised 1:1 to an invasive strategy plus OMT versus OMT alone. The combined primary endpoint was all-cause mortality and non-fatal myocardial re-infarction at 1 year. We enrolled 251 patients (n=125 invasive vs. n=126 conservative) from May 2014 to September 2018. Almost half were female. The trial was terminated prematurely due to slow recruitment. A Kaplan-Meier estimate of event-free survival revealed no difference in the primary combined endpoint (invasive 18.5% [23/124] vs. conservative 22.2% [28/126]; p=0.39) or in all-cause mortality alone (invasive 10.5% [13/124] vs. conservative 11.1% [14/126]; p=0.88). There was less angina at 3 months (p<0.001) in the intervention arm. Non-fatal reinfarction (invasive 9.7% [12/124] vs. conservative 14.3% [18/126]; p=0.22) and unplanned revascularisation (invasive 1.6% [2/124] vs. conservative 6.4% [8/126]; p=0.10) were non-significantly more frequent after OMT alone. Conclusion: The trial was underpowered to provide a definitive conclusion regarding the primary endpoint. An intervention-guided strategy did, however, result in less angina, reinfarction and unplanned revascularisation but did not improve survival

The impact of processes of care on myocardial infarct size in patients with ST-segment elevation myocardial infarction:Observations from the CRISPAMI trial

\u3cp\u3eBackground: Primary percutaneous coronary intervention (PCI) is the most common method of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) in the United States. The intersection between processes of care and performance measures such as door-to-balloon (D2B) times and clinical trials evaluating novel therapies for STEMI has not been fully investigated. Hypothesis: Processes of STEMI care, incorporating clinical trial enrollment and randomization, in patients undergoing reperfusion with primary PCI in the Counterpulsation Reduces Infarct Size Pre-Percutaneous Coronary Intervention Acute Myocardial Infarction trial (CRISP-AMI) will conform to current standards of care. Methods: Patients enrolled in CRISP-AMI were included in the current analysis. Processes of care during reperfusion were recorded prospectively and compared between groups. Results: A total of 337 patients with anterior STEMI without cardiogenic shock were randomized in CRISP-AMI. Complete processes-of-care data were available for 303 patients (89.9%). In this cohort, 68.0% of patients underwent reperfusion within 90 minutes of hospital contact, and the median D2B time was 71 minutes. Time from hospital contact to informed consent was significantly different across different regions (North America, 45 minutes; India, 35 minutes; Europe, 20 minutes). Conclusions: In CRISP-AMI, reperfusion was accomplished in a timely fashion while incorporating informed consent and randomization among patients with anterior myocardial infarction. Further study of patients' comprehension and preferences during the informed-consent process in STEMI patients is warranted so that innovative drugs and devices can be safely and ethically tested.\u3c/p\u3

Impact of Non–Infarct-Related Artery Disease on Infarct Size and Outcomes (from the CRISP-AMI Trial)

Background Non-infarct-related artery (non-IRA) disease is prevalent in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the impact of non-IRA disease on infarct size and clinical outcomes in patients with acute STEMI. Methods The Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP-AMI) trial randomized patients to intra-aortic balloon counterpulsation (IABC) vs no IABC prior to percutaneous coronary intervention in patients with acute STEMI. Infarct size (% left ventricular mass) at 3-5 days post percutaneous coronary intervention and 6-month clinical outcomes were compared between patients with and without non-IRA disease (defined as ≥50% stenosis in at least one non-IRA). Results A total of 324 (96.1%) patients had anterior STEMI, of whom 34.9% had non-IRA disease. There was no difference in infarct size (% left ventricular mass) between patients with and without non-IRA disease (median 39% vs 39%; P = .73). At 6 months, there was no difference in rates of recurrent myocardial infarction (0.9% vs 0.9%; P = .78), major Thrombolysis In Myocardial Infarction bleeding (0.9% vs 0.5%; P = .77), or all-cause death (3.5% vs 2.4%; P = .61) in patients with and without non-IRA disease, respectively. Patients with non-IRA disease had a higher rate of new/worsening heart failure with hospitalization (8.8% vs 1.9%; P = .0050). Conclusions More than one-third of patients with anterior STEMI in the CRISP-AMI study had non-IRA disease. These patients had similar infarct sizes and rates of recurrent myocardial infarction, major bleeding, and all-cause death. Patients with non-IRA disease did have a higher rate of new/worsening heart failure with hospitalization. Further study is needed to understand the mechanisms of outcomes of patients with non-IRA disease