Researchers from the Netherlands found that a treat-to-target approach for cardiovascular risk factors in patients with rheumatoid arthritis was effective in reducing clinical and subclinical atherosclerosis; however, the researchers noted there was a “considerable” dropout in the study that could have limited the results, according to data recently published in Annals of the Rheumatic Diseases.

Benjamin Burggraaf, MD, and his associates at Franciscus Gasthuis & Vlietland Hospital in Rotterdam, the Netherlands, performed an open-label, randomized, controlled trial of 320 patients with rheumatoid arthritis (RA) who were younger than 70 years old (mean age, 52.4 years) without a prior history of cardiovascular disease (CVD) and diabetes mellitus. The patients received either usual care for traditional CVD risk factors or a treat-to-target approach using a prespecified protocol for treating hypertension, hyperlipidemia and hypertriglyceridemia, as well hemoglobin A_1c greater than 48 mmol/mol. A total of 219 patients (68.4%) finished the study after 5 years. The two groups were similar at baseline, but the treat-to-target group had significantly more women (77.2%) compared with the usual care group (62.0%).

The researchers compared the progression of carotid intima media thickness (cIMT) at baseline and 5 years, with secondary outcomes of nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass grafting, percutaneous coronary intervention, peripheral atherosclerotic arterial disease–related amputation, peripheral atherosclerotic arterial disease revascularization, and death due to cardiovascular causes.

“To account for the high dropout, all missing cIMT values after 5 years of follow-up were imputed with all available cIMT values (baseline, years 1-4) and treatment group as covariate,” the researchers said. “Assuming that unobserved cIMT values were missing at random, missing data were imputed with multiple imputation using the fully conditional specification method for seven cycles.”

Dr. Burggraaf and his colleagues found the treat-to-target group had lower mean cIMT progression (0.023 mm; 95% confidence interval, 0.011-0.036) at 5-year follow-up than did the group that received usual care for CVD risk factors (0.045 mm; 95% CI, 0.030-0.059; P = .028). At 5 years, there were no significant differences between treat-to-target and usual care groups regarding mean systolic blood pressure (124.6 mm Hg vs. 124.7 mm Hg, respectively; P = .97), treat-to-target treatment targets for blood pressure (72.4% for usual care vs. 75.9% for treat-to-target; P = .56) and mean HbA_1c (37.6 mmol/mol for treat-to-target vs. 37.0 mmol/mol for usual care; P = .39). The treat-to-target group also had fewer cardiovascular events (two events, 1.3%) compared with the usual care group (seven events, 4.7%; P = .048). There were five patients in the treat-to-target group who died during the study (4.7%), compared with seven patients (3.2%) in the usual care group (P = .51).

“Although the difference in cIMT progression between the groups was relatively small in absolute terms, the relative reduction in progression was almost 50% in favor of the treat-to-target group,” they noted. “In light of the reduction of cardiovascular events, these effects are, in our opinion, clinically relevant.”

Other limitations of the study included the use of cIMT as a “soft endpoint” for modern cardiovascular trials and the use of unblinded cIMT progression measurement. In addition, the researchers noted the study was underpowered, and they used data from a type 2 diabetes mellitus cohort to perform the power calculation, which carried a 50% reduction in CVD risk factors. “We had doubts whether this high risk would apply to patients with RA and therefore used a more conservative target of 20% reduction for cIMT progression,” the researchers said.

This study was funded by the Franciscus Gasthuis & Vlietland Hospital, the Foundation for Research and Development of the Department of Internal Medicine, and the Coolsingel Foundation, Rotterdam. One author reported being a consultant for and receiving lecture honoraria from Merck.

SOURCE: Burggraaf B et al. Ann Rheum Dis. 2019 Jan 4. doi: 10.1136/annrheumdis-2018-214075.

Treat-to-target approach for CVD risk factors decreased atherosclerosis in RA patients