| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Kailua-Kona, HI
Correspondence to: David K. Cundiff, 76-881 Hualalai Rd, Kailua-Kona, HI 96740
To the Editor:
In reviews of the treatment of venous thromboembolism, Hyers and colleagues1 2 3 and the researchers in the 263 articles that they referenced neglected to mention a randomized trial by Nielsen et al,4 5 comparing heparin and a phenprocoumon anticoagulation therapy with phenylbutazone therapy in patients with deep venous thrombosis (DVT). This is the only published randomized controlled trial comparing the treatment of DVT patients using standard anticoagulation therapy with control subjects who had not received anticoagulation therapy. It was a negative study with 1 of 48 anticoagulated patient dying of pulmonary emboli (PEs) and 0 of 42 patients receiving phenylbutazone therapy experiencing fatal PEs.
In the 1995 review, Hyers et al1 state, "Patients with DVT or PE should be treated with IV heparin or adjusted-dose subcutaneous heparin sufficient to prolong the activated partial thromboplastin time to a range that corresponds to a plasma heparin level of 0.2 to 0.4 U/mL. This grade A recommendation is based on level I studies in patients with PE6 and DVT.7 8 9
The placebo-controlled randomized trial by Barritt and Jordan6 of patients with PE is too old, small (n = 35), and flawed to be considered as proof of the efficacy of anticoagulant therapy.10 Barritt and Jordan6 made the diagnosis based on clinical suspicion. We now know that only about 27% of patients suspected of having PEs actually have the diagnosis confirmed by angiogram or lung scan.11 Of the five deaths in the control group, cases 1 and 4 had chronic septic cavitation of the lungs, with no recent embolization. The patient in case 2 had thrombophlebitis and thrombosis of the hepatic veins but no documented autopsy evidence of PE. In the patient in case 5, the cause of death was cerebral infarction. Consequently, only case 3 would meet a modern definition of fatal PE: "massive fresh emboli present in the main pulmonary artery, or in at least two lobar arteries, demonstrated post mortem in patients in whom no other cause of death was found."12
None of the other randomized trials cited in the later reviews concerning DVT or PE had control subjects who were not anticoagulated.7 8 9 13 14 15 16 Therefore, they do not provide "level 1" evidence of the efficacy of anticoagulant therapy in patients with PEs or DVT.
Heparin and vitamin K antagonists became the standard treatment for DVT and PE patients in the 1940s before the advent of randomized controlled trials to prove the efficacy of treatment. The US Food and Drug Administration (FDA) allowed them to be "grandfathered in" as the standard treatment of DVT and PE in the early 1960s when proof of efficacy became required for FDA approval. Low-molecular-weight heparins have been granted approval as indications for the treatment of DVT by virtue of randomized controlled trials showing equivalence with heparin in trials that do not include "un-anticoagulated" control subjects.
For the articles and FDA correspondence detailing the case for withdrawing the indications for therapy with anticoagulants (ie, heparin, low-molecular-weight heparins, and vitamin K antagonists) in the prophylaxis and treatment of venous thromboembolism, please see my Web site (http://hometown.aol.com/
dkcundiff/home.htm).
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
