Morbidity and mortality are improving but remain high among patients with the systemic autoimmune condition known as antiphospholipid syndrome (APS), a large, prospective European study found.

Among 1,000 patients enrolled in the Europhospholipid project, 17% of patients developed thrombotic events during the years 1999 to 2004, as did 15% of patients during the years 2004 to 2009, according to Ricard Cervera, MD, PhD, of the University of Barcelona in Spain, and colleagues.

“Therefore, it is imperative to increase the effort in determining the optimal prognostic markers and therapeutic measures to prevent these important complications of the APS,” they stated.

Among the clinical features of APS are stroke, transient ischemic attacks (TIA), deep vein thrombosis (DVT), and pulmonary embolism (PE), as well as obstetric complications including preeclampsia and early pregnancy loss. The condition also is associated with high titers of antiphospholipid antibodies and multiple other non-thrombotic manifestations such as seizures.

The syndrome can be primary or associated with another disease, usually systemic lupus erythematosus (SLE).

Little is known about how treatment has influenced the long-term outcomes of APS, with previous studies being small and of short duration.

A total of 82% of the cohort was female, and almost all were white. Mean age at the time of enrollment was 42.

The syndrome was primary in 53%, associated with SLE in 36%, and associated with other conditions such as lupus-like syndrome in the remainder.

During the 10 years of follow-up, which were divided into two 5-year periods, 42% of patients were lost to follow-up.

Among the thrombotic events that occurred, strokes were seen in 5% of patients, TIA in 5%, DVT in 4%, and PE in 4%.

In contrast, during a median of 6 years’ follow-up before the study period, stroke had occurred in 20%, TIA in 11%, DVT in 39%, and PE in 14%.

A total of 16% of women became pregnant during the decade-long study, and 73% of the pregnancies were successful. That represented a significant improvement over baseline, when the rate of live births was only 48%.

The most frequent obstetric complication was fetal loss before 10 weeks in 17% of the pregnancies. Intrauterine growth restriction was seen in 26% and premature birth in 48%.

In comparing primary APS patients with SLE-related APS, the researchers found that the SLE subgroup more often had arthritis (21% versus 3%), hemolytic anemia (16% versus 2%), livedo reticularis (21% versus 7%), and myocardial infarction (4% versus 1%).

Most patients received antithrombotic treatment with aspirin or other antiplatelet agents. During the first 5 years of the study, 35% of patients were on low-dose anti-aggregant medications, as were 28% in the next 5 years.

Oral anticoagulants were being taken by 40% of patients during the first 5 years and by 37% during the second 5 years. In 62% of anticoagulant users, the target international normalized ratio (INR) was 2 to 3, and in 38% the target was 3 to 4.

In the second 5-year period, 25% of patients on antithrombotic therapy and 5% of those not on the treatment developed thrombosis, while 8% and 2%, respectively, developed an obstetric complication.

There were 61 major bleeding events during the 10-year follow-up among patients on antithrombotic medications, with 25% being cerebral, 16% being gastrointestinal, and 8% being intra-abdominal. Ten were fatal.

The most common causes of death were serious thrombotic events, with myocardial infarction, strokes, and PE accounting for 37%. Infection, primarily bacterial, was the cause in 27% and hemorrhage in 11%.

The probability of survival at 5 years was 94%, decreasing to 91% at 10 years.

The observation that arterial events continue to occur despite current treatment strategies suggests that “this particular group of patients may need a higher anticoagulation target (INR 3-4) as well as strict control of comorbidities and prothrombotic factors,” the investigators wrote.

“This long-term study provides updated information on APS morbidity and mortality characteristics. Patients with APS still develop significant morbidity and mortality despite current treatment (mainly oral anticoagulants and/or anti-aggregant agents),” Cervera and colleagues concluded.