To Bleed or Not To Bleed…

Abstract

Wang et al (February 2010)1Wang C Zhai Z Yang Y for the China Venous Thromboembolism (VTE) Study Group et al.Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial.Chest. 2010; 137: 254-262Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar reported that thrombolytic therapy for pulmonary thromboembolism with one-half the dose of recombinant tissue-type plasminogen activator (rt-PA) was associated with similar clinical improvement as the full dose, but complications of bleeding were greatly reduced. This is a landmark study that addresses one of the main issues that limit the use of this therapy: concerns about bleeding complications. Ibrahim et al2Ibrahim SA Stone RA Obrosky DS Geng M Fine MJ Aujesky D Thrombolytic therapy and mortality in patients with acute pulmonary embolism.Arch Intern Med. 2008; 168: 2183-2192Crossref PubMed Scopus (32) Google Scholar had already shown, in a 15,000-patient cohort, that in patients with pulmonary thromboembolism receiving thrombolytics bleeding complications occur in approximately 5.3% of patients. Decreasing the frequency of that feared complication is a major step in the use of this therapeutic approach. To illustrate this better, we organized the data obtained from Wang et al in a 2 × 2 format (Table 1), from which we can calculate the attributable risk percentage (AR%), which is the percentage of bleeding complications that could be prevented among patients receiving a regular dose of rt-PA if they received a low dose rt-PA, with the following formula:Table 1Major Bleeding Complications in Patients From the Study by Wang et al1Wang C Zhai Z Yang Y for the China Venous Thromboembolism (VTE) Study Group et al.Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial.Chest. 2010; 137: 254-262Abstract Full Text Full Text PDF PubMed Scopus (206) Google ScholarBleeding ComplicationNo Bleeding ComplicationTotalIncidence, per 100 per yearNormal-dose rt-PA17365332Low-dose rt-PA11546517rt-PA = recombinant tissue-type plasminogen activator. Open table in a new tab rt-PA = recombinant tissue-type plasminogen activator. AR% = ([Incidence of bleedingFull dose of rt-PA − Incidence of bleedingLow dose of rt-PA]/Incidence of bleedingFull dose of rt-PA) × 100 = ([32/100 − 17/100]/[32/100]) × 100 = 46.8 = 47%. Furthermore, if we want to have a better idea of what this potential change in practice may do to the group of patients to which it is targeted, then we should look at the population attributable risk percentage (PAR%), calculated with the following formula: PAR% = ([Incidence of bleedingTotal population – Incidence of bleedingLow dose rt-PA]/Incidence of bleedingTotal population) ×100 = ([23.7/100 – 17/100]/23.7/100) ×100 = 28.2%. This represents the percentage of bleeding complications in the patient population with pulmonary thromboembolism who are given thrombolytics that is due to receiving the regular dose of rt-PA and could be eliminated by using a lower dose of rt-PA. Certainly, the treatment of pulmonary thromboembolism with the use of thrombolytics in hemodynamically unstable patients has the potential to save lives.3Hirsh J Guyatt G Albers GW Harrington R Schünemann HJ American College of Chest Physician Antithrombotic and thrombolytic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).Chest. 2008; 133: 110S-112SAbstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar We look forward to using thrombolytics in a safer manner, and even though more studies are needed to further validate the data presented in the study by Wang et al,1Wang C Zhai Z Yang Y for the China Venous Thromboembolism (VTE) Study Group et al.Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial.Chest. 2010; 137: 254-262Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar there is a lot of promise if we can achieve a clinically relevant therapeutic effect with a major decrease in side effects. To Bleed or Not To Bleed…: ResponseCHESTVol. 138Issue 6PreviewWe appreciate Dr Pena's comments on our article in CHEST (February 2010).1 Indeed, bleeding complication is one of the main concerns that limit the use of thrombolytic therapy for pulmonary thromboembolism (PTE).2 We appreciate Dr Pena's calculations using attributable risk percentage (AR%) (the percentage of bleeding complications that could be prevented among patients receiving a regular dose of recombinant tissue-type plasminogen activator [rt-PA] if they received a low dose rt-PA) and population attributable risk percentage (the percentage of bleeding complications in the population with PTE given thrombolytics that is due to receiving the regular dose of rt-PA and could be eliminated by using a lower dose of rt-PA, as described in Dr Pena's letter), which provide a better and clearer illustration for the benefit of 50 mg rt-PA in reducing bleeding complications. Full-Text PDF