Rheum Patients on HCQ: Stick With It or Face Heart Consequences

High levels of adherence to prescribed antimalarial drugs for lupus and rheumatoid arthritis (RA) was associated with markedly lower cardiovascular event rates in one Canadian province, researchers found.

Rates for a composite of myocardial infarction, stroke, and venous thromboembolism was nearly 30% lower among patients with RA or systemic lupus erythematosus (SLE) whose filled prescriptions indicated they took these agents on at least 90% of days (adjusted HR 0.71, 95% CI 0.61-0.82), relative to those with adherence less than 90%, according to Hui Xie, PhD, of Simon Fraser University in Vancouver, British Columbia, and colleagues.

As well, when patients who took antimalarials -- mostly hydroxychloroquine (HCQ) -- with 90% adherence, the risk for major cardiovascular events was lower by about the same degree (aHR 0.72, 95% CI 0.64-0.81) compared with patients who never refilled their prescriptions, the researchers reported in Arthritis Care & Research. The risk reduction was particularly great for patients 65 and older.

But any less than 90% adherence seemed to provide no heart benefit at all. Xie and colleagues calculated a hazard ratio of 1.01 when comparing those with sub-90% adherence with patients who gave up the medications. And the results were similar when the group used an 80% threshold for adherence.

Antimalarials such as HCQ are prescribed for their anti-inflammatory effects. Inflammation is also a driver of cardiovascular disease, and past studies have shown that, indeed, these drugs have anti-lipid and anti-thrombotic activity.

But to take advantage of these effects, patients must actually swallow the pills. Xie and colleagues noted that plentiful previous research has established that real-world medication adherence in both RA and SLE is "suboptimal," to put it mildly.

To see how actual adherence might affect cardiovascular risk in RA/SLE patients prescribed antimalarials, the researchers turned to health records in British Columbia, where residents have universal access to provincial health insurance. They pulled data spanning 1990 to 2015, identifying 16,700 people with either RA or SLE who had been prescribed HCQ or, rarely, similar agents. (Nearly 90% had RA.)

Adherence was tracked for each 90-day period during which antimalarial prescriptions were in force. The median among all patients was 33 of these periods; mean follow-up was 9 years.

Just under 60% of patients were rated as having zero adherence, which was considered discontinuation. Some 22% achieved at least 90% adherence, and 19% were "non-adherent," i.e., had adherence of 1% to 89%.

During follow-up, 13.2% of patients experienced at least one event included in the composite cardiovascular outcome.

Besides the level of adherence, the major factor affecting event rates was age. Patients 65 and older with at least 90% adherence saw a 41% decrease in risk (aHR 0.59, 95% CI 0.48-0.72) relative to those with lesser adherence. For younger patients, however, the risk reduction was much smaller: just 17% and not statistically significant (aHR 0.83, 95% CI 0.68-1.03).

Associations between cardiovascular risk and the degree of adherence did not seem to differ whether patients had RA versus SLE.

Limitations included the reliance on administrative records and lack of data on potential confounders, such as health-seeking behaviors that might correlate with adherence. Information on important risk factors for cardiovascular disease was also unavailable. As well, Xie and colleagues noted that the records did not include reasons for discontinuation, which might have been recommended by physicians.

Comment