Anticoagulant monitoring, Troponin level and C reactive protein testing

There are so many reasons for distributed diagnostic testing and many testing locations beyond the traditional central diagnostics lab.  

Our review of the evidence and interviews with key opinion leaders, found in this series, shows: products and technologies that can offer central-lab quality testing but faster results and ease of interpretation bring real gains in terms of patient benefit, healthcare efficiencies and wider societal returns.  

In this second part, we look at the benefits of distributed diagnostics for anticoagulant monitoring, troponin level testing, and C reactive protein testing. We start with anticoagulant monitoring in the home.   

Anticoagulant monitoring in the home

  • Improved quality of life 
  • Greater treatment ownership by patients 
  • Reduced pressure on public healthcare services

People who live with long-term health conditions want and need to lead as normal life as possible. Frequent healthcare appointments can be hugely disruptive to family and work life.  

A striking example of this are people with atrial fibrillation, the post heart surgery population and those with other heart conditions who are on long term anticoagulant therapies such as warfarin. Because of the complex pharmacodynamics of warfarin, the levels of this drug in the body must be checked frequently to ensure that it is in the correct therapeutic window.  Not having the right level can lead to dangerous blood clots or uncontrolled bleeding events. Although direct oral coagulants (DOAC) are now available, warfarin currently accounts for around 20% of anticoagulant prescriptions in the UK.  

During titration, patients may need to attend a clinic once or twice a week to have a blood test, with regular checks required thereafter. Clearly, self-testing in the home would be beneficial. Additionally, as self-testing may be done more frequently at home, the likelihood of adverse events can be reduced. 

A large number of controlled trials demonstrate the safety of home testing. A 2016 Cochrane Review​ (1)​, which synthesised 28 randomised controlled trials involving a total of 8950 patients, concluded that the use of home test devices significantly reduces blood clotting events and mortality. There was up to a halving of these adverse events depending on the regime employed. 

A more recent Mayo Clinic study provides real-world evidence for the value of self-testing. The study followed 383 mechanical heart valve patients for a median of 3.1 years. 145 undertook self-monitoring while 238 patients were monitored exclusively during clinic visits. The time in therapeutic range was very similar between the two groups: 66.6% for at-home versus 67.2% for in-clinic testing. There was no difference in the rate of adverse events or mortality when controlled for age​ (2)​. 

It is clear that anticoagulant level home testing can be of great benefit for patients.  

We spoke to Bryn Sage, CEO of Inhealthcare: a leading provider of remote patient monitoring in the UK. Inhealthcare enable warfarin self-testing services across a number of NHS areas.

Our technology allows people with long-term heart conditions to stay on top of their health without the hassle of time-consuming hospital or clinic appointments. The INR self-testing service can reduce pressures on busy NHS clinics and allow staff to spend more time with patients who need care the most. We have rolled out similar services in the North East of England, Northern Ireland and Scotland and Greater Manchester. This is tried and tested technology which is playing a crucial role in increasing access to NHS care, reducing hospital admissions and improving patient outcomes.

The service has demonstrated excellent outcomes. At County Durham and Darlington Foundation Trust, 70% of patients improved the time spent in therapeutic range, reducing the risk of stroke by a half. Importantly, the service is inclusive. It works for everyone. Patients can opt to use an automated phone call if an app doesn’t work for them.

Troponin level testing by paramedics or in the physician’s office

  • Cost savings
  • Fewer hospital admissions
  • Reducing patient travel distance

Most patients suffering with acute myocardial infarction (AMI), commonly known as a heart attack, do not present with diagnostic ECG changes. Therefore, the use of cardiac necrosis biomarkers has become essential to diagnose and stratify patients presenting with chest pain. Both the cardiac-I (cTnI) and cardiac-T (cTnT) troponin isoforms are well established as highly specific biomarkers for the diagnosis of AMI. Indeed, a variety of lab-based and point-of-care systems provide cardiac troponin measurement including the widely used Abbott iStat and Roche Cobas h232 platforms.  

However, it is challenging to use these conventional tests to confirm an AMI diagnosis from only a single-point measurement with a time series of measurements required over the course of 3-6 hours. More recently, high-sensitivity troponin tests (defined as being able to measure troponin levels in >50% of a healthy reference population) have been shown to enable 0/1-hour ‘rule-out’ diagnostic pathways, which can potentially rule-out as many as 30% of patients presenting to ER with chest pain using a single-point measurement on arrival.  

This ability to more quickly diagnose and rule out patients using high-sensitivity troponin tests has driven a significant development effort over the past decade to bring high-sensitivity measurements to point-of-care based platforms. This is starting to bear fruit with the first point-of-care devices delivering high-sensitivity troponin test performance now approved for use in the EU, including the Quidel Triage True and the Siemens Atellica vTLI platforms. It is expected the first FDA-approved devices will follow shortly with the first benchtop system (Pathfast) having gained approval earlier this year. 

Several recent and ongoing studies reflect the degree of interest in using troponin level for chest pain triage. They show that how the distribution of existing diagnostic systems can reduce unnecessary trips to EDs without compromising patient safety, alongside other benefits. 

The ARTICA study in the Netherlands with 863 people not only evaluated patient outcomes but also calculated cost savings from troponin point-of-care testing carried out by ambulance staff. Patients deemed low-risk (by their history, ECG, age and specific risk factors) were assigned to the ambulance-based POC test arm or were admitted for standard hospital assessment. The mean 30-day healthcare costs were significantly lower (- €611) while the incidence of major cardiac events was comparable between the two study arms​ (15)​.  

Studies using modelling rather than real-world cost data have reported similar findings​ (16)​​ (17)​. There are, however, acknowledged challenges in incorporating ambulance troponin readings into care pathways – for example, determining exactly where diagnostic responsibility lies.  While tests taken in ambulances may have to be repeated in hospital for high-risk cases, ambulance-based triage could nonetheless save many unnecessary trips to ER for low -risk patients. 

Other benefits of this care model are not easily quantified. For many people, home life responsibilities, work, travel to the ED and long waiting times all combine into a stressful and potentially expensive experience that should be avoided if possible. In many countries, overcrowding of EDs is a persistent problem. Therefore it is in patients’ and healthcare providers’ interests to ensure that only those that really need to be there attend. The logistical hurdles and costs associated with attending a distant ED may therefore present a distinct business case for distributed diagnostics.  

An innovative study in rural New Zealand attempted to quantify the cost savings not only for the healthcare service but also to the patients themselves. The Rural Accelerated Chest Pain Pathway (RACPP) that incorporates troponin point-of-care testing was found to reduce median healthcare costs by NZ$977 and median patient borne costs by NZ$344​ (18)​. 

We spoke to Dr Rory Miller, Department of General Practice and Rural Health, University of Otago, New Zealand about the success of the RACPP programme. 

The RACPP has been shown to safely reduce the number of patients with chest pain that required to be transferred from rural health facilities, including general practices, to urban emergency departments by up to 44%.

These transfers would ordinarily take up to 2 hours each way in the New Zealand setting, which is a considerable saving. This means that these patients can stay closer to their workplaces, their families and their homes. It also means that the patients’ usual doctors and nurses are able to perform the assessment and then initiate risk reduction strategies to improve cardiovascular health.  Only patients who will truly benefit are transferred, which improves trust in the system and unburdens busy and overstretched ambulance services and emergency departments. The RACPP has been implemented widely in rural and urban community settings and is incorporated into many regional guidelines.”  

C reactive protein testing in the physician’s office

  • Combating antimicrobial resistance
  • Ruling out causes

Antimicrobial resistance (AMR) – the natural evolutionary consequence of widespread antibiotic use – is widely recognised as one of the most urgent challenges we face. Already, more than 1 million people die due to AMR each year (19). A landmark UK study raises the spectre that, by 2050, AMR may grow to a point where operations that are now routine, such as C-sections or hip replacements, are no longer safe, resulting in AMR becoming a significant drag on economic growth (20). Slowing the rise of AMR is therefore in everyone’s interest. 

Antibiotic use can be optimised using a variety of diagnostic approaches. In the first instance, it is a question of differentiating bacterial from viral infections, and only prescribing antibiotics for the former. In addition, molecular methods can be used to identify bacteria and known antibiotic resistance genes. However, molecular methods are not seen to be fully reliable because any strains identified may be commensal and resistance genes do not perfectly correlate with phenotypic resistance.  

Traditional microbiological methods for ascertaining resistance, on the other hand, typically have a time to results in the order of days, making methods for rapid determination of susceptibility highly desirable. Instruments for rapid testing whether strains are susceptible to antibiotics are emerging. 

The vast majority of antibiotic prescriptions are made in primary care, making this setting an important first line of defence against AMR. A large proportion of these prescriptions are for respiratory tract infections (RTIs). These are often self-limiting and/or viral in origin and therefore antibiotic treatment is of no use. Inappropriate overuse of antibiotics in primary care is therefore a major driver of antibiotic resistance. 

Measurement of C-reactive protein levels as an inflammation marker can aid the differentiation of serious bacterial-origin infections from other less serious and viral cases. A number of point-of-care CRP devices are on the market and their usage in primary care differs between countries.  

However, a growing pool of high-quality clinical trials demonstrates that POC testing does indeed reduce inappropriate antibiotic prescribing without damaging patient outcomes. For example, a 2022 Cochrane review of 12 trials including a total of 10,218 patients concluded use of CRP testing in primary care significantly reduced antibiotic prescribing with no difference in patient recovery rate​ (6)​. 

A review of health economic studies also suggests that CRP testing can provide a cost benefit in the short term​ (7)​. However, the same review also underscores that it is hard to put a monetary value on and account for the avoidance of additional antibiotic resistance in the longer term. Nevertheless, the example of CRP testing shows that moving diagnostics closer to the patient can have wider and longer-term societal benefits. 

We spoke to Naomi Chant, Associate Director of Professional Diagnostics at Una Health, UK suppliers of the Aidian QuikRead Go CRP assay platform.

Una Health proudly partners with Aidian to bring C-reactive protein testing to the point of care. As a UK distributor of point-of-care diagnostics, our mission is to transform the patient journey and improve health outcomes and Aidian’s QuikRead Go helps us achieve this. Our customers have integrated CRP testing into a number of different healthcare settings, from community diagnostic centres to the patient’s bedside in their own home. This empowers them to make prompt clinical decisions, with diagnostic certainty beyond clinical symptoms alone. This has a positive impact on antimicrobial stewardship by reducing unnecessary prescriptions, ruling out infections where they otherwise may be treated with an antibiotic. This is backed by randomised controlled trials showing reduced rates of antibiotic prescribing with the use of CRP point-of-care testing.

In times when our healthcare system is stretched and antimicrobial resistance is a significant threat to public health, never has the adoption of CRP testing at the point-of-care been more important.

In the next part of the series, we move from general diagnostics such as CRP testing to more specific diagnostics, be this for virus identification – to differentiate Flu A, Flu B and Covid in acute care – or genotyping in acute care (and pharmacies) to provide pharmacogenetic insight into drug responses. We also consider the huge value of distributed diagnostics in enabling Hepatitis C elimination in hard-to-reach communities.

Elena Boland

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