What is it about?
This is a comment to address several issues in the recent Review "Freund Y, Cohen-Aubart F, Bloom B. Acute pulmonary embolism: a review. JAMA. 2022;328(13):1336-1345."
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Why is it important?
First, the authors stated that smoking is not associated with higher rates of venous thromboembo- lism(VTE).However,inameta-analysisthatincluded3 966 184 people and 35 151 VTE events, the VTE risk increased by 10.2% for every additional 10 cigarettes per day or by 6.1% for every additional 10 pack-years of smoking.2 Second,thisarticle1statedthatthehemodynamicresponse toPEdependsonthesizeoftheocclusion.1However,inameta- analysisthatincluded194studiesand5251patientswithsaddle PE,whichisdefinedasstraddlingthebifurcationofthemainpul- monaryarterytrunk,thehemodynamicoutcomesofsaddlePE were comparable with that of other PE types.3 Third,theincidencesofPEamongpatientswithsyncopein thestudiescitedbytheauthorswere0.6%and2.2%.1However, inacross-sectionalstudy,PEwasconfirmedin17.3%of560pa- tients who were hospitalized for a first episode of syncope.4 Therefore, I am concerned that the incidence of PE in patients with syncope may have been underestimated in this article.1 Fourth, this article suggested that for intermediate-risk PE, early use of apixaban or rivaroxaban within 72 hours after initiation of low-molecular-weight heparin (LMWH) yields a better outcome compared with later use, and it also sug- gested that an early switch to dabigatran is also effective and safe.1 An increased initial dose of apixaban or rivaroxaban for intermediate-risk PE usually does not require a LMWH lead- in. However, patients with intermediate-high-risk PE are rec- ommended to receive LMWH anticoagulation on the first 2 to 3 days.5 The results of the study by Chopard et al cited in the article1 indicated that early use (within 72 hours of admis- sion) of apixaban or rivaroxaban was associated with shorter length of hospital stay and similar low rates of death and bleeding compared with delayed use of these medications in patients with intermediate-high-risk PE. Nonetheless, the ESC/ERS guidelines recommend LMWH typically for 5 days before switching to dabigatran or edoxaban.5 Because the study by Chopard et al was a retrospective post hoc analysis, and the PEITHO-2 study was a single-group noncontrolled trial,1 use of LWMH for no more than 72 hours prior to start- ing direct oral anticoagulants remains questionable until higher-level evidence becomes available.
Perspectives
DrXiongchallengestheassertioninourReview1thatsmok- ing is not a risk factor for PE, citing a meta-analysis that sug- gests a slight increased risk of VTE with smoking.2 We agree that it is possible that smoking may be a risk factor for VTE. However, the authors of this meta-analysis acknowledged the potential cofounding effect of body mass index. Further- more, the risk of smoking seems limited to provoked VTE and mainly driven by the confounding factors of cancer and other comorbidities.3,4 Xiong also challenges the statement in our Review that the severity of PE depends on its size and the pre- existing cardiac status of the patient. The meta-analysis cited by Xiong only suggested that a certain type of large PE (saddle PE) may not have a different prognosis than others.5 How- ever, that study reported a significant increased risk of death for massive PE compared with submassive and nonmassive PE (odds ratio, 29; 95% CI, 5-189), which is consistent with what was reported in our Review. Of note, that meta-analysis5 was published after the inclusion period for articles in our Review.1 The reported 17% rate of PE among patients with syncope in the study by Prandoni et al6 is not relevant for patients with a suspicion of PE, but rather, it is relevant for a selected sub- group of patients who were admitted to the hospital for a first episode of syncope. The studies cited in our Review included datafromapproximately10 000patientsanddemonstratethat the rate of PE in patients with isolated syncope is very low. In addition, we believe that the suggestion in our Review that oral anticoagulants can be introduced after 2 to 3 days of LMWH therapy in patients with intermediate-risk PE, which in- cludes intermediate-high-risk PE, aligns with the ESC guide- lines. The minimum period of 5 days of LWMH applies to pa- tients with high-risk PE.
Dr Wei Xiong
Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Read the Original
This page is a summary of: Review of Pulmonary Embolism, JAMA, February 2023, American Medical Association (AMA),
DOI: 10.1001/jama.2022.22232.
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