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28th March 2022
Both recurrent cardiovascular events (CVs) and death have been found to occur mainly within the first 6 months after the primary event according to a real-world analysis of registry data by researchers from the Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.
Cardiovascular disease (CVD) is the leading cause of deaths and disability worldwide and the World Health Organization estimates that CVD is response for 17.9 million lives lost each year. Despite falls in the mortality rates of CVD across Europe, more than 4 million people continue to die each year from the disease, with more than 1.4 million dying prematurely, before the age of 75 years. Moreover, recurrent cardiovascular events are not uncommon and one study among patients with acute coronary syndrome (ACS) found that 9% of patients experienced a recurrent cardiovascular event in the post-ACS setting during a median follow-up of 1 year.
But which factors are associated with an increased risk of recurrent CVs and death among secondary prevention patients, and when are these most likely to occur, was the subject of the present, registry-based study by the Finnish team. They undertook a retrospective analysis, using hospital data, of adult patients who experienced their first atherosclerotic cardiovascular disease (ACVD) event between 2012 and 2016. The team defined an ACVD event as a myocardial infraction (MI), unstable angina (UA), ischaemic stroke (IS) or a transient ischaemic attack (TIA). In addition, a recurrent event as a new diagnosis of the same condition as the index event, a minimum of 7 days from the first episode and all mortality data were retrieved from the hospital database.
Characteristics of cardiovascular events
In total, 48,405 adults with a median age of 71.5 years (53.8% male) were followed for a mean of 2.2 years. Among the whole cohort, 40.1% had an IS, 29.4% and MI and 19.5% a TIA as their index event. Co-morbidities included hypertension (12.9%) and diabetes (16.7%).
Among the current CVs, death was the most common subsequent event (61.5%) and a recurrent event occurred in 38.5% of patients. It was also clear that the category of subsequent events mirrored the initial episode (i.e., a second MI after the first). The cardiovascular events rate also increased after each recurrence. For instance, the combined recurrent/deaths events rate increased from 13.4 per 100 patient-years for the first event, to 36.8 for the third recurrent event.
In terms of the time to the recurrent event, after 6 months, 14% of patients had suffered any recurrent event or had died. This stabilised over time, so that after 5 years, 41.5% of patients had either suffered an event or died.
When considering the risk factors most significantly associated with risk of subsequent cardiovascular events, this increased with each increased year of age (hazard ratio, HR = 1.02 (95% CI 1.02 – 1.02, p < 0.001). Other significant factors included the presence of diabetes (HR = 1.21, 95% CI 1.11 – 1.32, p < 0.001) and hypertension (HR = 1.18). The risk of death was also significantly associated with male gender (HR = 1.18) but the only co-morbidity was diabetes (HR = 1.63, 95% CI 1.53 – 1.73, p < 0.001). Moreover, male gender and diabetes were also significantly associated with the risk of recurrency to death.
The authors concluded that given their findings, an acute CV event should be promptly followed by secondary prevention measures.
Toppila I et al. Cardiovascular event rate and death in high‐risk secondary prevention patient cohort in Finland: A registry study Clin Cardiol 2022
6th December 2021
A Comirnaty booster dose in those over the age of 50 provides a greater than 90% vaccine effectiveness, irrespective of whether individuals had been previously fully vaccinated with ChAdOx1-S (AstraZeneca) or Comirnaty (BNT162b). This was the finding of a study by a team from the UK Health Security Agency, UK, which is available online but not published in a peer-reviewed journal.
With evidence that the efficacy of COVID-19 vaccines wanes 20 weeks after vaccination, the Joint Committee on Vaccination and Immunisation (JCVI) in the UK issued a statement highlighting the need for a booster dose of COVID-19 vaccines in an effort to combat the virus during the winter months. Moreover, after a review of the available data on booster responses, the JCVI advised a preference for the Comirnaty vaccine as the booster dose irrespective of which product was used to provide the initial full vaccination.
In the present study, the UK team sought to estimate the real-world effectiveness of a single Comirnaty booster dose in those aged 50 years and older. The researchers compared vaccination status in this patient cohort, who were symptomatic for COVID-19 and with a positive PCR test result. Data was obtained from the National Immunisation Management System (NIMS) and a booster dose was defined as one given 140 days or more after a second vaccination dose. Vaccine effectiveness was adjusted in regression models for age, deprivation, ethnicity, care home residence status and co-morbidities. The analysis was also stratified by the primary vaccination received, i.e., either ChAdOx1-S (AstraZeneca) or Comirnaty and vaccine effectiveness assessed at several time points e.g., 2 to 6 days post booster dose and 14 or more days later.
For the primary analysis, the team compared vaccine effectiveness in those who received a booster with those who had been fully vaccinated but without a booster dose. In a secondary analysis, they determined the absolute vaccine effectiveness which was the difference in rates of infection between those who had two doses (at least 140 days apart) and a booster with those who were unvaccinated.
There were 271,747 eligible tests in people 50 years and older, of which 13,568 (5%) were unvaccinated with the remainder being fully vaccinated with either ChAdOx1-S or comirnaty (BNT162b)
The vaccine effectiveness from a BNT162b booster in those who were fully vaccinated with ChAdOx1-S was 87.4% (95% CI 84.9 – 89.4) and 84.4% (95% CI 82.8 – 85.8%) in those fully vaccinated with BNT162b.
In the secondary analysis, compared with unvaccinated individuals, those fully vaccinated with a primary course of ChAdOx1-S had an absolute vaccine effectiveness of 93.1% (95% CI 91.7 – 94.3%) and 94% (95% CI 93.4 – 94.6%) in those fully vaccinated with BNT162b.
Interestingly, when compared with those who were fully vaccinated but had not received a booster dose, the vaccine effectiveness after 20 or more weeks was 44.1% for the ChAdOx1-S vaccine and 62.5% for BNT162b.
In their conclusion, the authors wrote ‘our study provides real world evidence of significant increased protection from the booster dose against symptomatic disease in those aged over 50 years of age irrespective of which primary course was received.’
3rd December 2021
The effectiveness of allergen immunotherapy (AIT) in allergic rhinitis (AR) patients both with and without asthma has been confirmed in a 9-year retrospective analysis by researchers from the Paediatric Pulmonology and Allergy, Children’s Doctor Service, Heidelberg, Germany.
Allergies represent an abnormal immune system reaction to otherwise harmless allergens and in the UK, AR is estimated to affect 10-15% of children and 26% of adults. In addition, patients with AR can also suffer with asthma as a co-morbidity, with studies suggesting that 10% to 40% of AR patients have asthma. Furthermore, the presence of AR is associated with an incremental adverse impact on the disease-specific quality of life in patients with asthma and the level of asthma control.
Allergen immunotherapy (or desensitisation treatment) involves exposure to increasing doses of an allergen such as grass pollen, dust mite, or cat dander. AIT can be given via the subcutaneous or sublingual route, both of which have been shown to be effective treatment for patients with AR. Nevertheless, there is a recognised lack of information from studies on the effectiveness of AIT in real-world studies and over the longer term.
In order to address this gap in the evidence, the German researchers undertook the Real World effectiveness in allergy immunotherapy (REACT) study, primarily to assess the efficacy of AIT over a period of years. Using a retrospective, observational, propensity score matched cohort study, the team analysed health insurance claims from 2007 to 2017 and included AR patients with and without asthma and who had received an AIT prescription. These individuals were then propensity-score matched with AR individuals (also with or without asthma) but who had not been prescribed AIT. The primary outcome of the study was set as AR prescriptions in each follow-up year and secondary outcomes included asthma prescriptions, severe asthma exacerbations and any changes in the individual’s asthma treatment steps.
Between 2007 and 2017, 115,098 individuals had at least one AIT prescription, of whom, 46,024 with a mean age of 29.5 years (53% male) were propensity score matched. In addition, 14,614 AR patients with AR and co-existing asthma (mean age, 28.3 years, 54% male) were also matched with controls. However, over the 9 years, the study population declined, leaving 3692 individuals in the main cohort and 1142 with co-existent asthma.
When compared to control patients, AIT use was consistently associated with greater reductions in both AR and asthma prescriptions. In addition, there was a significantly greater likelihood that patients using AIT would have an asthma treatment step-down (p < 0.0001) and a reduction in severe asthma exacerbations (p < 0.05).
The authors concluded that their study had confirmed the real-world effectiveness of AIT as evidenced by sustained reductions in AR and asthma prescriptions, prevention of asthma exacerbations, and improved and sustained long-term asthma control.
Fritzching B et al. Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. Lancet Regional Health Europe 2021
19th November 2021
Atezolizumab and nivolumab have been found to prolong overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) cancer say researchers from Hoffmann-La Roche, Basel, Switzerland. NSCLC accounts for 85% of all lung cancers although nearly 40% of patients are diagnosed at stage 4, which has a poor prognosis, warranting systemic therapy. Treatment of NSCLC can be achieved with platinum-based chemotherapy although many patients relapse and in such cases, mono-therapy with the chemotherapeutic agent, docetaxel, has been found to be effective.
In recent years it has been discovered that developing tumours are capable of evading the immune system by avoiding checkpoint signals designed to prevent uncontrolled activation of T lymphocytes. Monoclonal antibodies including nivolumab and atezolizumab, work to either inhibit checkpoint PD-1 surface receptors (nivolumab) or its ligand, PD-L1 (atezolizumab) thereby blocking these receptors and signals, enabling the immune system to combat the tumour. Although both monoclonal antibodies are approved for use in NSCLC, there is a lack of head-to-head studies comparing these two agents even in comparison to docetaxel.
For the present study, researchers examined real-world studies contained within the US nationwide electronic health record, in which patients with advanced NSCLC and prior platinum-based therapy, who had been started on either atezolizumab, nivolumab or docetaxel. They included adults (18 years and over) diagnosed with locally advanced and/or metastatic NSCLC, none of whom had been previously treated with one of the three agents. The team also only included patients with at least 6 months of follow-up data and set the primary endpoint as overall survival.
In total, 3336 patients were included in the analysis with 206 receiving atezolizumab, 500 docetaxel and 2630 nivolumab. Patients in the atezolizumab and nivolumab groups were of a similar mean age, 68.3 and 67.3 years respectively while those in the docetaxel group were slightly younger with a mean age of 65.6 years.
Compared to docetaxel, use of atezolizumab was associated with a significantly longer survival (adjusted hazard ratio, aHR = 0.79, 95% CI 0.64 – 0.97, p = 0.02) even among those with different cancer stages. In contrast, the adjusted hazard ratio for atezolizumab compared with nivolumab was 1.07 (95% CI 0.89 – 1.28, p = 0.47) and this did not differ between patients at different cancer stages. However, the authors recognised that their analysis may not have been sufficiently powered to detect a difference between these two treatments.
The authors concluded that their real-world data suggested that atezolizumab and nivolumab produced a longer overall survival than docetaxel among those who had failed to respond to platinum-based chemotherapy.
Ramagopalan S et al. Comparative Effectiveness of Atezolizumab, Nivolumab, and Docetaxel in Patients With Previously Treated Non–Small Cell Lung Cancer. JAMA Netw Open 2021
7th December 2020
Real-world data can be derived from patient registries and are of value because they illustrate whether the expected efficacy determined in a randomised trial holds up in practice. Using information held in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a team from the Centre for Dermatology, Salford, UK, examined the comparative effectiveness of two biologics, secukinumab and ustekinumab used in patients with moderate to severe psoriasis, defined in terms of a psoriasis and area severity index (PASI) of 12 or more prior to starting with either biologic. The PASI serves as a measure of disease severity with scores above 10, indicating at least moderate disease severity. The researchers restricted the drug initiation dates to on or after September 2013 (when both drugs became available) and before September 2018, to allow for patients to have completed at least 12 months of therapy. The primary outcome for the study was the difference in the proportion of patients who achieved a PASI of 2 or lower (i.e. virtually disease free) after 12 months of therapy. The authors used the results of a recent RCT in which the two biologics were studied head-to-head, as a baseline to compare the effectiveness data derived from the BADBIR registry.
A total of 1231 patients were included, 917 receiving ustekinumab (mean age 45 years, 40% female) and the remainder secukinumab (mean age 46 with 38% female). A PASI at 12 months post-treatment was available for only 42% and 45.5% of those given secukinumab and ustekinumab respectively. Secukinumab was superior to ustekinumab in achieving a PASI of 2 (relative risk = 1.28, 95% CI 1.06 – 1.55). However, a further and important finding from the BADBIR registry data was that the estimate of efficacy from the RCT appeared much lower in practice. For example, secukinumab and ustekinumab were 17.5% and 15.1% less effective than the RCT data would suggest.
Commenting on these findings, the authors suggested that given this discrepancy, clinicians should aim to inform patients prescribed either drug that the true effectiveness was likely to be lower than expected based on the results shown in the clinical trial.
You ZZN et al. Randomised trial replication using observational data for comparative effectiveness of secukinumab and ustekinumab in psoriasis. A study from the British Association of Dermatologists Biologics and Immunomodulators register. JAMA Dermatol 2020