ObjectivesTo describe the incidence of adverse events (AEs), reactogenicity symptoms, menstrual changes and overall self-rated improvement in health and well-being after COVID-19 ...vaccination.DesignVAC4COVID is an ongoing prospective, active observational, post-authorisation cohort safety study (PASS) of UK-approved vaccines for COVID-19 disease.SettingThe study is conducted through a secure website (www.vac4covid.com) by MEMO Research, University of Dundee, UK.Participants16 265 adult (18 years or older) UK residents with a valid email address and internet access.InterventionsAny UK-authorised COVID-19 vaccination.Main outcome measuresThe outcomes reported in this interim analysis include AEs, reactogenicity-type AEs (headache, fatigue, muscle or joint pain, fever, nausea, dizziness or local vaccine reaction), menstrual changes and reported improvement in overall health and well-being.Results11 475 consented participants (mean age 54.8 years) provided follow-up data between 2 February and 5 October 2021 (mean follow-up duration 184 days), by which date 89.2% of participants had received two vaccine doses. 89.8% of 5222 participants who completed a follow-up questionnaire in the 7 days after any COVID-19 vaccination reported no AEs. The risk of experiencing any event (not necessarily vaccine-related) requiring hospitalisation was less than 0.2%. 43.7% of post-vaccination follow-up records reported improvement in health and well-being. Reactogenicity-type reactions were more common in the week after the first dose of ChAdOx1 than BNT162b2 (7.8% vs 1.6%), but this relationship was reversed after the second dose (1.3% vs 3.1%). 0.3% of women reported menstrual symptoms after vaccination; no differences between vaccine type or dose order were detected.ConclusionsThe study provides reassuring data on low rates of AEs after COVID-19 vaccination. Differences in reactogenicity-type AE profiles between ChAdOx1 and BNT162b2 and between first and second doses of these vaccines were observed.Trial registration numberISRCTN95881792; Pre-results.
Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested ...beneficial cardiovascular effects of allopurinol.
To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease.
Prospective, randomised, open-label, blinded endpoint multicentre clinical trial.
Four hundred and twenty-four UK primary care practices.
Aged 60 years and over with ischaemic heart disease but no gout.
Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care.
The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis.
From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (
= 2979) or the usual care arm (
= 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21);
= 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20);
= 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective.
The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis.
The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout.
The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies.
This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426).
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in
; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.
Oxidative stress participates in the development and exacerbation of cardiovascular diseases (CVD). The ability to promptly quantify an imbalance in an individual reductive-oxidative (RedOx) state ...could improve cardiovascular risk assessment and management. Derivatives-reactive oxygen metabolites (d-ROMs) are an emerging biomarker of oxidative stress quantifiable in minutes through standard biochemical analysers or by a bedside point-of-care test. The current review evaluates available data on the prognostic value of d-ROMs for CVD events and mortality in individuals with known and unknown CVD. Outcome studies involving small and large cohorts were analysed and hazard ratio, risk ratio, odds ratio, and mean differences were used as measures of effect. High d-ROM plasma levels were found to be an independent predictor of CVD events and mortality. Risk begins increasing at d-ROM levels higher than 340 UCARR and rises considerably above 400 UCARR. Conversely, low d-ROM plasma levels are a good negative predictor for CVD events in patients with coronary artery disease and heart failure. Moreover, combining d-ROMs with other relevant biomarkers routinely used in clinical practice might support a more precise cardiovascular risk assessment. We conclude that d-ROMs represent an emerging oxidative-stress-related biomarker with the potential for better risk stratification both in primary and secondary cardiovascular prevention.
Abstract Objectives This study sought to assess an echocardiographic approach (scar imaging echocardiography with ultrasound multipulse scheme eSCAR), based on existing multipulse ultrasound scheme, ...as a marker of myocardial scar in humans, compared with cardiac magnetic resonance assessing late gadolinium enhancement (CMR-LGE). Background The detection of myocardial scar impacts patient prognosis and management in coronary artery disease and other types of cardiac disease. The clinical experience with echocardiography suggests that the reflected ultrasound signal is often significantly enhanced in infarcted myocardial segments. Methods Twenty patients with a recent ST-segment elevation myocardial infarction (STEMI) (cases) and fifteen patients with absent CMR-LGE (negative controls) were imaged with both the eSCAR pulse-cancellation echo and CMR-LGE to assess their potential association. Results Scar was detectable at CMR-LGE in 19 of 20 STEMI patients (91%), whereas all (100%) demonstrated eSCAR at echocardiography. In the 19 STEMI patients in whom CMR-LGE was detected, regional matching between eSCAR and CMR-LGE was total, although the segmental extent of detected scar was not always superimposable, particularly in the most apical segments, a region in which eSCAR demonstrated undersensitivity for the true extent of scar. Conclusions A 2-dimensional multipulse echocardiography allows detection of myocardial scar, reliably matching the presence and site of CMR-LGE at 30 days after STEMI, or its absence in negative controls.
Objective:
To observe the effect of the xanthine oxidase inhibitors Allopurinol and Febuxostat on blood pressure in adults with chronic hyperuricemia.
Design and method:
This was a sub-study of the ...Febuxostat versus Allopurinol Streamlined Trial (FAST). FAST was a randomised controlled trial comparing the cardiovascular safety of febuxostat and allopurinol in individuals with symptomatic hyperuricemia previously receiving allopurinol. At the screening visit, patients were invited to participate in the Blood Pressure (BP) sub-study. A validated BP monitor and an instruction booklet were provided. Each set of home BP measurements was taken over four consecutive days, three times each in the morning and evening. BP was recorded at baseline (on allopurinol therapy), after 7-days allopurinol washout, and 8 weeks after randomisation to febuxostat or allopurinol. Differences in BP in the allopurinol and febuxostat group were evaluated. The relationship between serum uric acid level reductions and BP changes was also assessed.
Results:
Between December 2012 and January 2014, 298 FAST participants consented to the BP sub-study. 223 participants who submitted a complete set of BP data were included in the analysis; 104 were randomised to Allopurinol and 119 to Febuxostat. Baseline characteristics were balanced between groups. Overall mean change in BP from washout to 8 weeks of randomised treatment was not significant in either group Mean BP change in Allopurinol arm: SBP -0.10 mmHg (95% CI -1.76,1.56), p = 0.9; DBP 0.50 mmHg (95% CI -1.82,2.81), p = 0.6. Mean BP change in Febuxostat arm: SBP -0.77 mmHg (95% CI -4.20,2.67), p = 0.7; DBP -0.41 mmHg (95% CI -2.56,1.73), p = 0.7. No significant BP differences were observed between groups at each time point. Reduction in serum uric acid by > 60 μmol/L at 8 weeks on either therapy was not associated with statistically significant changes in BP.
Conclusions:
There was no significant difference in the effect of allopurinol or febuxostat on blood pressure after 8 weeks of randomised therapy in the FAST study. Larger reductions in serum uric acid at 8 weeks had no effect on BP change.
•Timely first response during pandemics benefit from globally harmonised risk mitigation options.•Global acceptance, preparedness and alignment are key in the early phase of a local ...outbreak.•Citizens' awareness addressing individual and grouproles creates obedience of imposed measures.
This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11, 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.
Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated ...with clopidogrel's metabolism.
The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone.
Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria.
After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001).
A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes PHARMCLO; NCT03347435).
Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study ...aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.
ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.
Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years SD 6·8, 4321 75·5% males, and 5676 99·2% white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio HR 1·04 95% CI 0·89–1·21, p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 95% CI 0·87–1·20, p=0·77).
In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.
UK National Institute for Health and Care Research.
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