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Take a look at a selection of our recent media coverage:

Ticagrelor reduces MACE compared to clopidogrel following stent implant

26th January 2023

Ticagrelor reduces the risk of ischaemic major adverse cardiac events compared to clopidogrel in patients following stent implantation

Chinese researchers from the University of Shanghai have reported that the combination of ticagrelor and aspirin reduced the incidence of ischaemic major adverse cardiac events (MACE) compared to clopidogrel and aspirin, following the implantation of emergency drug-eluting stents in patients with a ST-elevation myocardial infarction.

The use of dual anti-platelet therapy combining aspirin and a P2Y12 receptor inhibitor reduces recurrent MACE in patients undergoing a percutaneous coronary intervention (PCI) with drug-eluting stents. Despite the proven value of this combination treatment, it has become clear that continued high on-treatment platelet reactivity to adenosine diphosphate, is associated with adverse clinical events. In fact, there is evidence to suggest that between 4 and 30% of patients treated with clopidogrel fail to show an adequate platelet response. Moreover, use of ticagrelor has been shown to exhibit a lower level of high on-treatment platelet reaction in comparison to clopidogrel. Despite these findings, the reason for high on-treatment high residual platelet reactivity remain unclear but elevated levels of fibrinogen despite treatment with drugs such as clopidogrel have been found to be independently associated with the risk of ischaemic myocardial injury following elective PCI in patients treated with clopidogrel.

In the current study, the Chinese team examined the impact of fibrinogen on residual platelet reactivity after an emergency drug-eluting stent implantation in patients treated with either aspirin and clopidogrel, or aspirin and ticagrelor, over a 12-month period following their stent implant. The team used a prospective design and included patients undergoing PCI and who were prescribed aspirin 100 mg with clopidogrel 75 mg daily or aspirin and ticagrelor 90 mg twice daily for at least 12 months. The researchers measured both on-treatment platelet reactivity and the fibrinogen concentration and which was divided into quartiles. The endpoint of interest was ischaemic MACE, which was a composite of several adverse cardiovascular outcomes e.g., unplanned revascularisation, ischaemic stroke.

Ticagrelor and MACE

A total of 919 patients aged between 62.9 and 65 years and of whom, between 76.8 and 83.8% were male, were included in the final analysis, with 55.8% prescribed clopidogrel.

The rates of MACE were significantly elevated among patients prescribed clopidogrel compared to ticagrelor (HR = 1.72, 95% CI 1.21 – 2.43, p = 0.004).

Overall, MACE occurred in 14.3% of the entire cohort and the highest risk was found in patients with high residual platelet reactivity and those in the highest quartile of fibrinogen levels (HR = 10.02, 95% CI 4.67 – 21.46, p < 0.001).

The authors concluded that both a high fibrinogen level and high residual platelet reactivity could be used to identify patients at risk of an ischaemic event over a 12 month period and suggested that ticagrelor provided a better prognosis than clopidogrel.

Citation
Yao Y et al. The impact of high on-treatment platelet reactivity and fibrinogen levels on ischemic events in patients with ST elevation myocardial infarction: a prospective observational study. Int J Clin Pharm 2023

Alcoholic spirit intake associated with increased risk of ventricular arrhythmias

23rd December 2021

Only increased alcoholic spirit intake has been found to be associated with a higher risk of ventricular arrhythmias among regular drinkers

Increased alcoholic spirit intake is associated with an increased risk of ventricular arrhythmia but this elevated risk is absent for other forms of alcoholic beverages. This was a key finding from a retrospective analysis by a team from the Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Australia.

Higher intakes of alcohol are generally considered to damage the cardiovascular system although light to moderate alcohol intake appears to be protective. The term ‘holiday heart syndrome‘ has been coined to describe any alcohol-induced atrial arrhythmias and/or conduction disturbance associated with heavy consumption in a person without other clinical evidence of heart disease. Whilst the relationship between atrial arrhythmias and alcohol has become well recognised, there is a paucity of data linking alcohol intake with ventricular arrhythmias (VA). In fact, the available evidence is inconsistent, with some data showing a non-significant association whereas other studies suggesting that heavy alcohol consumption is an important contributing factor. Moreover, the influence of the type of alcoholic drink on VA or even sudden cardiac death (SCD) is also uncertain.

For the present study, researchers used information held in the UK Biobank which provides data on approximately half a million community-dwelling individuals aged 40 to 69 years across the UK. For their analysis, the researchers focused on incident cases of VA but excluded those with a previous history of the condition and former drinkers. The amount of alcohol intake was reported in terms of a standard drink, defined as 8g of alcohol and the average number of standard drinks consumed per week. For alcohol intake, the team also considered the type of each beverage consumed and created regression models which adjusted for several covariates such as age, sex, race, education.

Findings

Data for a total of 408,712 individuals with an average age of 58.3 years (52.1% female) were included in the analysis and who were followed up for a median duration of 11.5 years. The median alcohol intake for the whole cohort was 8 drinks per week although 5.5% of the group reported having never consumed alcohol.

There were a total of 1733 incident VA events and 2044 SCDs which occurred during the follow-up period. Overall, there was no statistically significant association between total alcohol intake and the risk of VA. However, when considered by type of alcoholic beverage, only alcoholic spirit intake was linearly linked with an increased risk of VA among those consuming greater than 14 drinks per week (hazard ratio, HR = 1.15, 95% CI 0.98 – 1.34) and this became statistically significant with more than 28 drinks per week (HR = 1.33, 95% CI 1.03 – 1.73).

For SCD there was a U-shaped distribution of risk with the lowest risk at around 7 drinks per week.

The authors concluded that they were unable to find an association between total intake of beer, cider and wine and VA and that only increased alcoholic spirit intake was linked to a higher risk. In fact, wine intake was associated with a lower risk of SCD although the authors suggested that these findings require clarification from experimental studies.

Citation

Tu SJ et al. Alcohol consumption and risk of ventricular arrhythmias and sudden cardiac death: An observational study of 408,712 individuals Heart rhythm 2021

Dual analytical approach reveals causal link between smoking and outcomes in COVID-19

1st October 2021

A dual analytical approach combining observational and Mendelian randomisation data suggests smoking linked to worse outcomes in COVID-19.

Throughout the COVID-19 pandemic, several important risk factors for more severe disease have become apparent including male sex, increased age and cardiovascular co-morbidities. Whether or not being a current smoker affects COVID-19 outcomes is less clear with some analyses indicating a higher risk of worse outcomes, whereas others reviews suggest a reduced risk . One solution to untangling this ambiguity is the adoption of a dual analytical approach to data analysis, for example, by comparing the results from observational studies with those from a Mendelian randomisation study. In a Mendelian randomisation (MR) study, the underlying assumption is that a genetic variant influences only the variable of interest and since genetic variants are randomly allocated at birth, MR is less susceptible to confounding which is a problem in observational studies. Genetic analysis can be used to identify variants associated with particular traits. For example, tobacco and alcohol use are known to have heritable behaviours and in one study, researchers identified 566 genetic variants in 406 loci associated with multiple stages of tobacco use, e.g., initiation, cessation, and heaviness (i.e., the number of cigarettes smoked per day).

Using a dual analytical approach to examine the relationship between smoking and outcomes in COVID-19, a team from the Nuffield Department of Primary Care Health Sciences, University of Oxford, UK, turned to data held within the UK Biobank. The researchers separately explored the relationship between smoking and COVID-19 using findings from both observational studies and Mendelian randomisation. For the MR study, researchers used established genetic proxies for smoking initiation and smoking heaviness (i.e., the number of cigarettes smoked per day). The results were analysed using multivariate logistic regression analysis adjusted for several variables including age, sex, ethnicity and several co-morbidities.

Findings

For the observational analysis, there were 421,469 individuals with a median age of 68.6 years (55.1% female). Current smokers were found to have an overall higher risk of hospitalisation (adjusted odds ratio, aOR = 1.80, 95% CI 1.26 – 2.29) and mortality (aOR = 4.89, 95% CI 3.41 – 7.0).

Similarly, in the Mendelian randomisation analysis, genetic propensity to initiate smoking was associated with a higher risk of hospitalisation (aOR = 1.60, 95% CI 1.13 – 2.27), but not mortality (aOR = 1.35, 95% CI 0.82 – 2.22, p = 0.23). For genetically predicted higher number of cigarettes smoked per day, the risk of hospitalisation was also higher (aOR = 5.08, 95% CI 2.04 – 12.66) and risk of death (aOR = 10.02, 95% CI 2.53 – 39.72).

Discussing their findings, the authors said that this was the first study to adopt a dual analytical approach to assess the relationship between smoking and outcomes from COVID-19. They concluded that the congruence between the two methods indicated that a lifelong predisposition to smoking and smoking heaviness supported a causal effect (found in the observational analysis) of smoking on COVID-19 severity.

Citation

Clift AK et al. Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort. Thorax 2021

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