Advertisement

Thrombolytics Decrease Mortality in Elderly Patients with Unstable Pulmonary Embolism

Published:January 29, 2013DOI:https://doi.org/10.1016/j.amjmed.2012.11.009
      SEE RELATED ARTICLE p. 304
      Prior reports
      • Stein P.D.
      • Matta F.
      Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
      • Dalen J.E.
      Thrombolytics and vena cava filters decrease mortality in patients with unstable pulmonary embolism.
      in the Journal have made it clear that thrombolytic therapy is the treatment of choice in patients with pulmonary embolism who are hemodynamically unstable.
      Stein and Matta
      • Stein P.D.
      • Matta F.
      Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
      reported that thrombolytic therapy dramatically decreased the mortality of pulmonary embolism in patients who were hemodynamically unstable, defined as in shock or requiring ventilator support. Stein and Matta
      • Stein P.D.
      • Matta F.
      Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
      reported that the mortality in 21,390 patients with unstable pulmonary embolism treated with thrombolytics was 15% compared with 47% in 50,840 patients treated with standard anticoagulant therapy (risk reduction=68%). In 6630 unstable patients who were treated with thrombolytics and an inferior cava filter, the mortality was even lower (7.6%), essentially the same as in patients with stable pulmonary embolism treated with standard anticoagulant therapy (7.9%).
      • Stein P.D.
      • Matta F.
      • Keyes D.C.
      • Willyerd G.L.
      Impact of inferior cava filters on in-hospital case fatality rates from pulmonary embolism.
      These results were not the findings of a randomized clinical trial. They were the clinical outcome of therapeutic decisions by thousands of physicians who treated more than 2 million patients with pulmonary embolism in US hospitals from 1999 to 2008.
      Thrombolytic therapy was administered to only 30% of 72,230 hemodynamically unstable patients.
      • Stein P.D.
      • Matta F.
      Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
      In the present issue of the Journal, Stein and Matta
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      show that the patients least likely to receive thrombolytics were the oldest patients and those with 1 or more comorbid conditions. Thirty-eighty percent of 29,850 patients aged 60 years or less received thrombolytics compared with 16% among 10,580 patients aged more than 80 years.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      The difference in therapy in patients with and without comorbid conditions was even greater. Eighty percent of patients without a comorbid condition received thrombolytics compared with 19% in those with 1 or more comorbid conditions
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      defined in the Charlson Comorbidity Index.
      • Charlson M.E.
      • Pompei P.
      • Ales K.L.
      • MacKenzie C.R.
      A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
      These results are not surprising; the complications of thrombolytic therapy increase with increasing age and the presence of comorbid conditions.
      • Mikkola K.M.
      • Patel S.R.
      • Parker J.A.
      • Grodstein F.
      • Goldhaber S.Z.
      Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis.
      As expected, the mortality increased with increasing age.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      However, in each age group the mortality was significantly lower in those treated with thrombolytics.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      In patients aged 60 years or less who had 1 or more comorbid conditions, the mortality of those treated with thrombolytics was 16% compared with 39% without thrombolytics.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      In patients aged more than 80 years, the mortality with thrombolytics was 25% compared with 57% without thrombolytics.
      Among patients of all ages with 1 or more comorbid conditions, the mortality was 20% in those treated with thrombolytics as opposed to 47% in those without thrombolytics.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      Among patients of all ages with no comorbid conditions, the mortality was 8% in those treated with thrombolytics as opposed to 41% in those without thrombolytics.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      The patients who were at greatest risk of the complications of thrombolytics were the 1180 patients aged more than 80 years who had comorbid conditions. The mortality in those who received thrombolytics was 25% compared with 57% in 8490 patients who did not receive thrombolytics.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      These findings make it clear that advanced age and the presence of comorbid conditions are not contraindications to thrombolytic therapy in patients with hemodynamically unstable pulmonary embolism. The benefit of thrombolytic therapy in terms of lower mortality clearly outweighs the risk of fatal bleeding.
      In the approximately 4 decades since the first clinical trial of thrombolytic therapy for pulmonary embolism,
      The urokinase pulmonary embolism trial A national cooperative study.
      the indications for thrombolytic therapy have been controversial.
      • Dalen J.E.
      • Alpert J.S.
      • Hirsh J.
      Thrombolytic therapy for pulmonary embolism: is it effective? Is it safe? When is it indicated?.
      In my opinion, the reports by Stein and Matta
      • Stein P.D.
      • Matta F.
      Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
      • Stein P.D.
      • Matta F.
      Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
      make it clear: In the absence of contraindications, patients with hemodynamically unstable pulmonary embolism, including elderly patients with comorbid conditions, should be treated with thrombolytics.

      References

        • Stein P.D.
        • Matta F.
        Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused.
        Am J Med. 2012; 125: 465-470
        • Dalen J.E.
        Thrombolytics and vena cava filters decrease mortality in patients with unstable pulmonary embolism.
        Am J Med. 2012; 125: 429-430
        • Stein P.D.
        • Matta F.
        • Keyes D.C.
        • Willyerd G.L.
        Impact of inferior cava filters on in-hospital case fatality rates from pulmonary embolism.
        Am J Med. 2012; 125: 478-484
        • Stein P.D.
        • Matta F.
        Treatment of unstable pulmonary embolism in the elderly and those with comorbid conditions.
        Am J Med. 2013; 126: 304-310
        • Charlson M.E.
        • Pompei P.
        • Ales K.L.
        • MacKenzie C.R.
        A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
        J Chronic Dis. 1987; 40: 373-383
        • Mikkola K.M.
        • Patel S.R.
        • Parker J.A.
        • Grodstein F.
        • Goldhaber S.Z.
        Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis.
        Am Heart J. 1997; 134: 69-72
      1. The urokinase pulmonary embolism trial.
        Circulation. 1973; 47 (II-1-I08)
        • Dalen J.E.
        • Alpert J.S.
        • Hirsh J.
        Thrombolytic therapy for pulmonary embolism: is it effective?.
        Arch Intern Med. 1997; 157: 2550-2556