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Data on antithrombotic therapy for essential thrombocythemia ‘imprecise, inconsistent’
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Whether the benefits of antithrombotic therapy outweigh the risks in patients with essential thrombocythemia is unclear based on insufficient evidence, according to a systematic review published in Annals of Internal Medicine.
“The available evidence is imprecise, inconsistent and at high risk [for] bias,” Deborah M. Siegal, MD, MSc, assistant professor in the department of medicine at McMaster University, and colleagues wrote. “Adequately powered randomized trials are needed to clarify the net clinical benefit of antithrombotic therapy in essential thrombocythemia and the subgroups that will derive the most benefit.”
Essential thrombocythemia — a myeloproliferative neoplasm characterized by thrombocytosis —carries a risk for thrombotic and hemorrhagic events. Between 11% and 29% of patients with essential thrombocythemia develop thrombosis. Case fatality rates range between 33% and 51% for thrombosis and 1% to 10% for hemorrhage.
Moreover, controlled trials in the general population show that aspirin increases major bleeding by 58%.
“Reducing thrombotic risk is the primary goal of therapy to prevent morbidity and mortality,” Siegal and colleagues wrote. “However, the quality of the evidence, the magnitude of risk reduction, and the risk for adverse effects with antithrombotic therapy in patients with essential thrombocythemia are unclear.”
Siegel and colleagues searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, among other databases, to identify studies on the risks and benefits of antithrombotic therapy in patients with essential thrombocythemia.
Researchers reviewed 24 observational studies — 18 comparative and six single group — involving 6,153 patients (median age, 53 years; 62% women) followed for 31,711 patient-years.
Most patients who received antithrombotic therapy (n = 3,613 of 4,527; 80%) received low-dose aspirin (50 mg to 150 mg per day). Another 914 patients (20%) received high-dose aspirin (300 mg to 600 mg per day), dipyridamole or other agents.
Patients who did not receive antithrombotic therapy demonstrated incidence rates of five to 110 per 1,000 patient-years (median, 20) for thrombosis, three to 39 (median, 8) for any bleeding, and two to 53 (median, 6) for major bleeding.
Incidence rates for patients not treated ranged from 0.26 to 3.48 (median, 0.74) for thrombosis, 0.48 to 11.04 (median, 1.95) for any bleeding, and 0.48 to 5.17 (median, 1.30) for major bleeding.
The most common bleeding sites with antiplatelet therapy included gastrointestinal and intracranial.
The researchers rated certainty of evidence as low or very low for all outcomes.
“Our studies confirm that patients with essential thrombocythemia are at high thrombotic risk (median baseline risk, 19.9 events per 1,000 patient-years) and may remain at high risk despite the use of antiplatelet therapy,” Siegal and colleagues wrote.
Limitations of the review included a lack of randomized trials, lack of uniform bleeding definitions, and insufficient data to analyze the effect of antithrombotic therapy in arterial vs. venous events.
Twenty-one of the 24 studies reviewed by researchers received a rating of serious risk for bias overall, Joel S. Bennett, MD, professor of medicine at Perelman School of Medicine at University of Pennsylvania, wrote in an accompanying editorial. Additionally, treatment effect estimates in 15 comparative studies varied widely, with an estimated median relative risk reduction of 0.74 (95% CI, 0.29-1.87).
“Unfortunately, this entirely justifiable conclusion provides no guidance for the internist or hematologist faced with an otherwise asymptomatic patient with essential thrombocythemia,” Bennett wrote. “Because the consequences with thrombosis can be devastating and irreversible, not treating such a patient with antiplatelet therapy can engender substantial anxiety in both the physician and the patient.
“Knowing the correct therapeutic approach would clearly be helpful, and this topic is ripe for a randomized clinical trial,” Bennett added. “However, in the absence of known cardiovascular risk factors, there are currently no data to compel physicians to treat asymptomatic patients with essential thrombocythemia with antiplatelet agents.” – by Chuck Gormley
Disclosure: Regional Medical Associates funded this study. Siegal reports nonfinancial support from Bayer and personal fees from Bayer, Bristol-Myers Squibb/Pfizer Servier, Novartis, and Portola outside the study. Please see the full study for a list of all other researchers’ relevant financial disclosures. Bennett reports no relevant financial disclosures.
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