Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK

© 2020 Author(s). Introduction: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. Methods and design: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP. The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (∼6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP. Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. Ethics and dissemination: The study was approved by the London - City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals

An Observational Study Assessing Immediate Complete Versus Delayed Complete Revascularisation in Patients with Multi-Vessel Disease Undergoing Primary Percutaneous Coronary Intervention.

Background: More than half of the patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have multi-vessel coronary artery disease. This is associated with worse outcomes compared with single vessel disease. Whilst evidence now exists to support complete revascularisation for bystander disease the optimal timing is still debated. This study aimed to compare clinical outcomes in patients with STEMI and multi-vessel disease who underwent complete revascularisation as inpatients in comparison to patients who had staged PCI as early outpatients. Methods and results: We conducted an observational cohort study consisting of 1522 patients who underwent primary PCI with multi-vessel disease from 2012 to 2019. Exclusions included patients with cardiogenic shock and previous CABG. Patients were split into 2 groups depending on whether they had complete revascularisation performed as inpatients or as staged PCI at later outpatient dates. The primary outcome of this study was major adverse cardiac events (consisting of myocardial infarction, target vessel revascularisation and all-cause mortality).834 (54.8%) patients underwent complete inpatient revascularisation and 688 patients (45.2%) had outpatient PCI (median 43 days post discharge). Of the inpatient group, 652 patients (78.2%) underwent complete revascularisation during the index procedure whilst 182 (21.8%) patients underwent inpatient bystander PCI in a second procedure. Overall, there were no significant differences between the groups with regards to their baseline or procedural characteristics. Over the follow-up period there was no significant difference in MACE between the cohorts (P = .62), which persisted after multivariate adjustment (HR 1.21 [95% CI 0.72-1.96]). Furthermore, in propensity-matched analysis there was no significant difference in outcome between the groups (HR: 0.86 95% CI: 0.75-1.25). Conclusions: Our study demonstrated that the timing of bystander PCI after STEMI did not appear to have an effect on cardiovascular outcomes. We suggest that patients with multi-vessel disease can potentially be discharged promptly and undergo early outpatient bystander PCI. This could significantly reduce length of stay in hospital

The Use of Novel Oral Anti-Coagulant's (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI).

This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal - Cardiovascular Pharmacotherapy following peer review. The version of record: Daniel A Jones, Paul Wright, Momin A Alizadeh, Sadeer Fhadil, Krishnaraj S Rathod, Oliver Guttmann, Charles Knight, Adam Timmis, Andreas Baumbach, Andrew Wragg, Anthony Mathur, Sotiris Antoniou, The Use of Novel Oral Anti-Coagulant’s (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI), European Heart Journal - Cardiovascular Pharmacotherapy, pvaa096, https://doi.org/10.1093/ehjcvp/pvaa096AIM: Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3 - 6 months for treatment of LV thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of Novel Oral Anti-Coagulant's (NOAC) compared to VKA for other indications such as DVT, PE and thrombo-embolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post AMI. In this study we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI. METHODS AND RESULTS: This was an observational study of 2,328 consecutive patients undergoing Coronary Angiography +/- Percutaneous Coronary Intervention (PCI) for AMI between May 2015- December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary end-point was rate of LV thrombus resolution with bleeding rates a secondary outcome.Left ventricular (LV) thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban, 36.5% and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (Previous MI, PCI, CABG), and cardiovascular risk factors (Hypertension, Diabetes, Hypercholesterolaemia).Over the follow up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs 64.4%, p = 0.0018, at 1 year), which persisted after adjusting for baseline variables (OR 1.8 95% CI 1.2-2.9). Major bleeding events during the f/u period were lower in the NOAC group, compared with VKA group (0% vs 6.7%, p = 0.030) with no difference in rates of systemic thromboembolism (5% vs 2.4%, p = 0.388). CONCLUSION: This data suggests improved thrombus resolution in post ACS LV thrombosis in patients treated with NOACs compared to vitamin K antagonists. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients' vs VKA treated patients. Thus, provides data to support a randomised trial to answer this question

Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study

KSR and this work are funded by an NIHR Doctoral Fellowship (DRF-2014-07-008

COVID-19 and changes in activity and treatment of ST elevation MI from a UK cardiac centre.

Background: The international healthcare response to COVID-19 has been driven by epidemiological data related to case numbers and case fatality rate. Second order effects have been less well studied. This study aimed to characterise the changes in emergency activity of a high-volume cardiac catheterisation centre and to cautiously model any excess indirect morbidity and mortality. Method: Retrospective cohort study of patients admitted with acute coronary syndrome fulfilling criteria for the heart attack centre (HAC) pathway at St. Bartholomew's hospital, UK. Electronic data were collected for the study period March 16th - May 16th 2020 inclusive and stored on a dedicated research server. Standard governance procedures were observed in line with the British Cardiovascular Intervention Society audit. Results: There was a 28% fall in the number of primary percutaneous coronary interventions (PCIs) for ST elevation myocardial infarction (STEMI) during the study period (111 vs. 154) and 36% fewer activations of the HAC pathway (312 vs. 485), compared to the same time period averaged across three preceding years. In the context of 'missing STEMIs', the excess harm attributable to COVID-19 could result in an absolute increase of 1.3% in mortality, 1.9% in nonfatal MI and 4.5% in recurrent ischemia. Conclusions: The emergency activity of a high-volume PCI centre was significantly reduced for STEMI during the peak of the first wave of COVID-19. Our data can be used as an exemplar to help future modelling within cardiovascular workstreams to refine aggregate estimates of the impact of COVID-19 and inform targeted policy action

Prior Coronary Artery Bypass Graft Surgery and Outcome After Percutaneous Coronary Intervention: An Observational Study From the Pan-London Percutaneous Coronary Intervention Registry.

Background Limited information exists regarding procedural success and clinical outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI). We sought to compare outcomes in patients undergoing PCI with or without CABG. Methods and Results This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry from 2005 to 2015. The primary end point was all-cause mortality at a median follow-up of 3.0 years (interquartile range, 1.2-4.6 years). A total of 12 641(10.2%) patients had a history of previous CABG, of whom 29.3% (n=3703) underwent PCI to native vessels and 70.7% (n=8938) to bypass grafts. There were significant differences in the demographic, clinical, and procedural characteristics of these groups. The risk of mortality during follow-up was significantly higher in patients with prior CABG (23.2%; P=0.0005) compared with patients with no prior CABG (12.1%) and was seen for patients who underwent either native vessel (20.1%) or bypass graft PCI (24.2%; P<0.0001). However, after adjustment for baseline characteristics, there was no significant difference in outcomes seen between the groups when PCI was performed in native vessels in patients with previous CABG (hazard ratio [HR],1.02; 95%CI, 0.77-1.34; P=0.89), but a significantly higher mortality was seen among patients with PCI to bypass grafts (HR,1.33; 95% CI, 1.03-1.71; P=0.026). This was seen after multivariate adjustment and propensity matching. Conclusions Patients with prior CABG were older with greater comorbidities and more complex procedural characteristics, but after adjustment for these differences, the clinical outcomes were similar to the patients undergoing PCI without prior CABG. In these patients, native-vessel PCI was associated with better outcomes compared with the treatment of vein grafts