Oral steroids can up CVD risk, even at low doses

Use of oral glucocorticoid is associated with an increased risk of cardiovascular diseases (CVDs), even at low doses of <5 mg prednisone-equivalent daily in patients with immune-mediated inflammatory diseases, a large study reveals.

“It was previously believed that less than 5 mg of prednisolone was safe long term, but even at this ‘low dose’ patients with immune-mediated inflammatory diseases have a doubling of their underlying risk of CVD,” said the researchers.

“These results highlight the importance of prompt and regular monitoring of cardiovascular risk … beyond diagnosis of inflammatory arthropathies and systemic lupus erythematosus, even when prescribing low prednisolone-equivalent doses [PEDs],” they added.

At 1 year follow-up, the absolute risk of CVDs was more than doubled with use of glucocorticoids at a daily PED of <5 mg compared with period of nonuse (cumulative incidence estimates, 3.8 percent vs 1.4 percent). [PLoS Med 2020;doi:10.1371/journal.pmed.1003432]

For patients taking higher PEDs of glucocorticoids, the cumulative risk of CVDs was increased in a dose-dependent manner, up to six times with use of ≥25 mg PED daily vs period of nonuse (cumulative incidence estimates, 8.9 percent vs 1.4 percent).

Similarly, cumulative risk at 5 years increased from 7.1 percent with nonuse to 28.0 percent with ≥25 mg PED daily.

Not only was low-dose glucocorticoid use associated with an increased risk of all-cause CVDs (hazard ratio [HR], 1.74), an excess risk was seen across a wide range of type-specific CVDs, including atrial fibrillation (HR, 1.69), heart failure (HR, 1.75), acute myocardial infarction (HR, 1.76), peripheral arterial disease (HR, 1.78), cerebrovascular disease (HR, 1.32), and abdominal aortic aneurysm (HR, 1.93). 

“[The] strong dose-dependent increases in hazards of [these broad spectrum of fatal and nonfatal CVDs remained] regardless of the underlying immune-mediated disease, its activity, and duration,” the researchers noted.

The population-based cohort study included 87,794 patients (mean age 56 years, 34.1 percent male) in UK primary care practices who had no prior CVD and were diagnosed with any of the six immune-mediate inflammatory diseases: inflammatory bowel disease, giant cell arteritis and/or polymyalgia rheumatic, rheumatoid arthritis, systemic lupus erythematosus, and/or vasculitis.

“Many individuals had known modifiable cardiovascular risk factors, including current smoking [24 percent], obesity [25 percent], or hypertension [25 percent],” the researchers pointed out.

In fact, the increase in absolute CVD risk in patients taking high-dose glucocorticoids was of similar extent to that of patients with established CVD or diabetes, which according to the researchers, warrants the need for intensive lifestyle modification interventions in this high-risk group.

“The dose-dependent increased risk of CVDs … supports the need for close monitoring of cardiovascular risk in patients diagnosed with immune-mediated inflammatory diseases during glucocorticoid treatment and in the period after therapy discontinuation,” the researchers stated.

They called for new treatment strategies that avoid long-term use of steroids and have better cardiovascular safety profile for treatment of immune-mediated inflammatory diseases.

“All patients requiring long-term steroid treatment should be prescribed the lowest effective steroid dose and have a personalized CVD risk prevention plan that takes into account current and prior steroid use,” advised the researchers.

“Our findings also emphasize the importance of rapid glucocorticoid dose tapering and discontinuation as soon as disease control is achieved, as well as the importance of evaluating the safety profile of alternative therapeutic options for patients with autoimmune-mediated inflammatory diseases,” they highlighted.