Glucocorticoids and Cardiovascular Events in RA Explained

Dr Ho So of the Chinese University of Hong Kong discussed his research into whether glucocorticoids — specifically prednisolone — for rheumatoid arthritis may increase the risk of major adverse cardiovascular events among these patients.

Professor Ho So is an assistant professor in the department of medicine and therapeutics at the Chinese University of Hong Kong.

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Transcript:

Disclaimer:

Any views and opinions expressed are those of the authors and/or participants, and do not necessarily reflect the views, policy or position of the Rheumatology and Arthritis Learning Network or HMP Global, its employees and affiliates.

RALN:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your host, Priyam Vora, and today we are talking with Dr. Ho So. So Dr. So is an assistant professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong. Today, we are going to discuss his research into whether glucocorticoids, specifically prednisolone, for rheumatoid arthritis may increase the risk of major adverse cardiovascular events among these patients. Thank you for joining us today.

Dr. Ho So:

Thank you for having me.

RALN:

Let's start with a very basic question. What prompted this research?

Dr. Ho So:

Right. There has been a great improvement in the management of patients with rheumatoid arthritis in the past two decades, and cardiovascular disease now became the major cause of morbidity and mortality for patients with rheumatoid arthritis. Despite the tremendous advancement in the therapeutics of rheumatoid arthritis, we still see an alarming rate of glucocorticoid use in daily clinical practice. We all know that rheumatoid arthritis and systemic glucocorticoid use are associated with increased risk of cardiovascular disease.

But quite interestingly, the latest rheumatoid arthritis management recommendation from ACR and EULAR are rather different in terms of the glucocorticoid use recommendation. ACR conditionally recommended the initiation of conventional synthetic DMARDs without a short-term glucocorticoid. On the other hand, EULAR recommended that short-term glucocorticoid should be considered when initiating csDMARDs, but should be tapered and discontinued as fast as clinically feasible. Whether there exists a cardiovascular safe dose or duration of glucocorticoid use in the treatment of patients with rheumatoid arthritis, it's still quite controversial and is obviously of great clinical interest. And that's why we performed this study trying to evaluate the risk of major cardiovascular adverse events in a group of patients exposed to chronic synthetic glucocorticoid use.

RALN:

Okay. Would you be able to describe the general outline of your study, like the number of patients and the parameters?

Dr. Ho So:

Absolutely. This was a population-based retrospective cohort study. We obtained data from the government database in Hong Kong. So we saw Hong Kong. So it's mainly Chinese patients. Adult patients with rheumatoid arthritis within the period of 2006 to 2015 were recruited. The key exclusion was a history of MACE before the diagnosis of rheumatoid arthritis. And the primary outcome of the study is the first occurrence of a MACE. And we use the time-varying Cox regression analysis to evaluate the association of glucocorticoid use and MACE, adjusting for multiple factors. For example, demographics, traditional cardiovascular risk factors, inflammation, as well as the usage of other anti-rheumatic medications. We also used a specific statistical method to try to control the confounder. We use the time-varying inverse probability treatment. So IPTW to SA sensitivity analysis to confirm the independent association of MACE and glucocorticoid use.

RALN:

And what did you find?

Dr. Ho So:

Right. We recruited altogether more than 12,000 patients with rheumatoid arthritis. And after a mean follow-up of 8.7 years, 7% of our patients developed incident MACE. So the risk of cardiovascular disease is real. And after controlling for multiple potential confounders, the usage of glucocorticoid of a dose equivalent to prednisolone, more than four milligram daily, was independently associated with about two times risk of MACE compared to no glucocorticoid use, while the usage of prednisolone less than five milligram daily did not appear to be associated with increased MACE risk.

RALN:

Okay. During your research, did you identify any trends in the occurrence of cardiovascular events across various demographic differences such as age, gender, socioeconomic factors, or smoking habits?

Dr. Ho So:

Yes, and as expected. We found that age, male sex, and some other traditional cardiovascular risk factors, for example, diabetes, hyperlipidemia, hypertension, were also independent predictors of MACE. And very interestingly, we also identified systemic inflammation as reflected by raised ESR or CLP was also independently associated with MACE, signifying that systemic inflammation really plays a role in accelerated atherosclerosis in patients with rheumatoid arthritis.

RALN:

Right. Right. Okay. You explained that doses of more than five milligram of prednisolone have been implicated in major adverse cardiovascular events. Does exposure over time also play a role? What duration of therapy appears to increase the risk of MACE?

Dr. Ho So:

Right, this is another very important point. We actually found a time-dependent increased risk of mace with glucocorticoid use higher or equal to prednisolone five milligram daily.There was a 7% increased risk per month of glucocorticoid usage.

RALN:

Right. Okay. What alternative treatments for rheumatoid arthritis would you recommend over prednisolone?

Dr. Ho So:

Right. This is a little bit difficult, but I know systemic glucocorticoids are very useful. They are very efficacious in controlling symptoms, but with the availability of so many other fast-acting efficacious therapeutic agents, I'm referring to the biological or targeted synthetic DMARDs, and obviously we also have an alternative of the more economical biosimilars. So I think we might need to consider earlier usage of all these biological or targeted synthetic DMARDs, particularly in those patients with risk factors. For risk factors, we are not just referring to those factors associated with long-term structural damage. We should also take into consideration the overall cardiovascular profiles.

RALN:

Right. Okay. For milder rheumatoid arthritis, are NSAIDs a good option there at least?

Dr. Ho So:

In fact, I think yes, although we know that some NSAIDs might also be associated with cardiovascular disease, but we think that these agents can help control inflammation. So the benefit might somehow overweight the harm. It's always about balancing the risk and benefits of various different agents. I think for patients who are symptomatic who are waiting for the effects of conventional synthetic DMARDs, NSAIDs should also be an option.

RALN:

Right, right. Okay. I know you touched upon this before, but I still want to ask you. Besides the time and dose-dependent factors, are there any patient specific risk factors that should be monitored or checked for before prescribing prednisolone for a longer duration of time?

Dr. Ho So:

Yes, this is a very good point. So in fact, if we really need to use systemic glucocorticoids, there are few points. So firstly, we should assess and screen for cardiovascular risk regularly. It is recommended by EULAR. We should also have a good control of all those modifiable risk factors. So DM, hypertension, hyperlipidemia, and stop smoking. And also very importantly, we need to have a good control of systemic inflammation. So we should have the rheumatoid arthritis disease controlled as fast as possible.

RALN:

Great. Thank you for that. Do you have any plans to expand this to a broader study?

Dr. Ho So:

Yes. In fact, our study just look at cardiovascular risk associated with glucocorticoid use. Other side effects of glucocorticoid use including infection, bone loss, or peptic disease risk, we have not examined these other side effects of long-term glucocorticoid use. We also did not examine whether a very low dose prednisolone is clinically efficacious because we found that prednisolone daily less than five milligram was not associated with increased cardiovascular risk, but whether this dose is actually clinically efficacious still has to be examined.

RALN:

Thank you so much for taking the time to talk to us. Once again for our listeners, that was Dr. Ho So providing us important insights into how glucocorticoids have an impact on cardiac complications among patients with rheumatoid arthritis. Thank you, Dr. So.

Dr. Ho So:

Thank you very much.

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