Q1. What was the reason for the initiation of the STROKESTOP II study?
In the STROKESTOP I sub-study, they measured NT-proBNP in 900 participants and found those with atrial fibrillation to have significantly higher NT-proBNP than those who did not have atrial fibrillation. With the knowledge that it could be useful to predict incident atrial fibrillation and the fact that it is associated with increased risk of stroke and mortality, the rationale was that it might be used to select those at highest risk that could benefit the most from screening.
Q2. What are the main highlights of the STROKESTOP II study?
It is a population-based cohort study, in which all 75 and 76-year-olds in the Stockholm region were randomised 1:1 to be invited to an atrial fibrillation screening program or to serve as the control group. Participants without known atrial fibrillation had NT-proBNP analysed and were stratified into low-risk (NT-proBNP<125 ng/L) and high-risk (NT-proBNP ≥125 ng/L) groups. These values were predefined from this sub-study and the study rationale.
The high-risk group was offered extended ECG screening, whereas the low-risk group performed only one single-lead ECG recording at the visit. In total, 6868 individuals accepted the screening invitation, of which 6315 (91.9%) did not have previously known atrial fibrillation.
In the high-risk group (59.6%), new atrial fibrillation was diagnosed in 4.4% resulting in a total new atrial fibrillation diagnosis in the whole group of 2.6%. The screening procedure resulted in an increase in known prevalence from 8.1% to 10.5% among participants, which is a 30% increase. Out of the participants in the high-risk groups, 28 had atrial fibrillation on their first visit, whereas only one participant in the low-risk group was found to have atrial fibrillation.
In a multivariable analysis of the high-risk group, NT-proBNP was a strong perspective for new atrial fibrillation prediction. 90% of those with previous atrial fibrillation were on oral anticoagulation (OAC) treatment and that is a change from the previous STROKESTOP trial, where it was 70%; but this is also the trend in the community. 94.5% of those with new atrial fibrillation were initiated on oral anticoagulant treatments after cardiologist assessment and 96% of all participants who started oral anticoagulant treatment were adherent to the treatment on one year follow up.
So, using NT-proBNP for risk stratification led to a similar proportion of new atrial fibrillation being detected, with only 59% of the participants recording ECGs for 2 weeks, as compared to the STROKESTOP I trial in which all the participants underwent the 2 weeks extended ECG screening procedures.
So, these are the main results from the STROKESTOP II base study.
Q3. Based on the study outcomes, what are the advantages of using NT-proBNP as a screening tool to predict elderly patients at high risk of atrial fibrillation?
NT-proBNP can predict an incident atrial fibrillation and using NT-proBNP of 125 ng/L for risk stratification led to a new atrial fibrillation diagnosis in 4.4% of the participants in a higher risk group. The total proportion of atrial fibrillation cases was as I said before similar to all participants undergoing ECGs in the STROKESTOP I trial. But this is something we will of course evaluate when will be looking at cost-effectiveness later on. We also studied the subgroup of participants with NT-proBNP over 900, so without previously known heart failure and they were only about 2% of the study population.
We found 30% to have atrial fibrillation in that group. We also discovered several serious cardiac comorbidities such as amyloidosis, aortic stenosis, regurgitation as well as chronic or critical ischemic heart disease. So that is the tool we can use in my opinion.
Q4. Should an NT-proBNP test be part of a health screening in elderly patients?
I could be a bit biased here in this question because I measure NT-proBNP quite a lot. Not only for the trial but also in the cardiac emergency and cardiac intensive care units.
NT-proBNP is a quantitative plasma biomarker for the presence and severity of hemodynamic cardiac stress and heart failure. End-diastolic wall stress, intracardiac filling pressures, and intracardiac volume seem to be the dominant triggers and it has a very high diagnostic accuracy in discriminating heart failure from other causes of dyspnoea. This is why it is used worldwide in heart failure diagnosis, treatment, and prognosis.
It is an independent predictor of mortality and other cardiac outcomes in patients with heart failure. Low NT-proBNP (<125 ng/L) is used according to guidelines as a rule-out test for heart failure.
We know it can predict incident atrial fibrillation but whether it can be used to screen for atrial fibrillation the way we do the STROKESTOP II trial is something we have yet to find out as the study is still ongoing. But screening with NT-proBNP in elderly patients could possibly be used for the early detection of relevant cardiac diseases including atrial fibrillation and left ventricular systolic dysfunction and it may help to identify patients at increased risk and at the same time allow targeted preventive measures to prevent progress or development of cardiovascular disease. But as always further studies will help guide us further.
