How much are we overtreating pulmonary emboli?

November 18th, 2018

A diagnosis of pulmonary embolism — a blockage of the pulmonary artery — can be very serious; acute PE leads to at least 50,000 deaths each year. These blockages are often caused by blood clots in the legs, a condition called “deep vein thrombosis.” But, as many researchers and clinicians have pointed out, all pulmonary emboli may not be equally dangerous.

The invention and subsequent widespread use of more sensitive high-resolution imaging tests like CT pulmonary angiography has led to far more detection of PE than prior to the use of this technology. However, many of these new diagnoses are for “subsegmental” PE, blockages found in offshoots of the pulmonary artery. These subsegmental PE are often found incidentally on unrelated scans, and often occur without without the usual PE symptoms such as coughing, shortness of breath or deep vein thrombosis.

There is little evidence to show that subsegmental PE is as harmful as symptomatic PE, or even clinically significant. In a 2010 study, French researchers found that using higher-sensitivity scans increased the proportion of patients diagnosed with subsegmental PE, but the 3‐month risk of thromboembolism for these patients did not change. Epidemiology data show that even as we are diagnosing 80% more PE since the advent of CTPA, the mortality rate from PE has only minimally decreased.

More than a quarter of diagnosed pulmonary emboli at one institution were overtreated

In a recent JAMA study, researchers from the McGill University Health Centre (including Dr. Ismael Raslan, a former Lown Vignette Competition winner!) tracked the rates of subsegemental PE and diagnosis at their institution. They found that about 28 percent of diagnosed pulmonary emboli may have been overtreated; 32 percent of diagnoses were for subsegmental PE without deep-vein thrombosis, and 87 percent of these were treated with anticoagulation.

There are no randomized controlled trials that test whether patients with subsegmental PE benefit from anticoagulant therapy versus observation. While the harms of subsegmental PE are unknown, the potential harm of treating patients with anticoagulants (blood thinners), such as increased risk of brain bleed or other major bleeding, should not be discounted. In a meta-analysis of 750 patients with subsegmental PE, there was no difference in PE recurrence or mortality between those given anticoagulants and those who were observed without therapy; but 8% of patients taking anticoagulants had bleeding. Other observational studies have found similar results, with no difference in PE recurrence based on therapy, but an increased risk of bleeding.

Fear of complications leads many doctors to treat PE, even if it may represent imaging artifact or is discovered incidentally.

Given unknown benefit of treatment and potential harms, why are we treating this type of PE at such high rates? The authors of the JAMA study write that “fear of complications” leads many doctors to treat PE, “even if it may represent imaging artifact or is discovered incidentally.” In an accompanying editorial, Dr. Lisa K. Moores at the Edward Hebert School of Medicine suggests that “practitioners have been reluctant to allow patients with documented acute PE to go untreated, particularly because older literature reported mortality rates for these patients.” However, many studies of patients with PE without deep vein thrombosis since then have shown that these patients can be safely managed with observation instead of anticoagulation, and guidelines have been updated since then.

For patients with only a subsegmental PE and no deep-vein thrombosis, “Doctors should explain to these patients that controversy exists as to the management of this condition, but it is possible that the risks outweigh the benefits of anticoagulation and, therefore, avoiding unnecessary anticoagulation is currently a reasonable approach,” write Dr. Pieter Cohen, general internist at the Cambridge Health Alliance and Dr. Michael Hochman, director of the Gehr Family Center for Implementation Science at the University of Southern California. 

Overtreatment of incidental subsegmental PE is widespread, partly because we are more afraid causing harm from not doing enough than we are of causing harm from doing too much. The fact that there are no randomized controlled trials to test the benefits and harms of anticoagulant treatment is frustrating. But with the evidence we currently have, the burden of proof should be on those who recommend medical therapy rather than observation for this particular diagnosis.