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Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients

Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients. Ajay K. Kakkar , M.B., B.S., Ph.D., Claudio Cimminiello , M.D., Samuel Z. Goldhaber , M.D., Rajiv Parakh , M.D., Chen Wang, M.D., Ph.D., and Jean-François Bergmann, M.D., for the LIFENOX Investigators*.

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Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients

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  1. Low-Molecular-Weight Heparinand Mortality in Acutely Ill Medical Patients Ajay K. Kakkar, M.B., B.S., Ph.D., Claudio Cimminiello, M.D., Samuel Z. Goldhaber, M.D., Rajiv Parakh, M.D., Chen Wang, M.D., Ph.D., and Jean-François Bergmann, M.D., for the LIFENOX Investigators* Zaki Abou Zahr Iman Andalib

  2. BACKGROUND • Venous thromboembolism is an importantcomplicationin hospitalized patients. • It is estimated that if thromboprophylaxis is not administered, deep vein thrombosis will develop in 10 to 20% of medical patients • and in 40 to 60% of patients undergoing major orthopedic surgery • Pharmacologic thromboprophylaxis has been proved to reduce the incidence of venous thromboembolism in both surgical patients and acutely ill medical patients.

  3. BACKGROUND • In surgical patients, thromboprophylaxishas been shown to reduce the incidence of fatal pulmonary embolism and the rate of death from any cause • in medical patients, studies have shown that thromboprophylaxisis associated with reductions in the rate of venous thromboembolicevents, including asymptomatic DVTs but not mortality • A meta-analysis of five studies involving medical patients indicated that prophylaxis may be associated with a reduction in the rate of fatal pulmonary embolism but not in the rate of death from any cause.

  4. Discussion • findings appear to be counterintuitive • pharmacologic prophylaxis has been shown to reduce the risk of venous thromboembolism, bincludingasymptomatic DVTs by at least 45% in hospitalized, acutely ill medical patients. • It has been assumed that the natural history of DVTs would be the • same in acutely ill medical patients compared to surgical patients • In Surgical patients asymptomatic proximal DVT have a higher risk of death than those with distal DVT • This assumption may be incorrect; • perhaps the natural history of deep-vein thrombosis differs between medical and surgical patients.

  5. Discussion • Compared to MEDENOX trial 1999 • which established the efficacy of the regimen of 40 mg of enoxaparin daily in acutely ill medical patients • showed a 25% reduction in mortality • favorable trend in overall survival associated with effective prophylaxis may not be only due to reduction deaths related to DVTs • but also in deaths from other causes, most likely cardiovascular events.

  6. Discussion • Multiple coexisting illnesses and other potential causes of death • might make fatal pulmonary embolism a less important determinant of mortality in this group than in surgical patients • thus diminishing the ability of pharmacologic prophylaxis to improve the overall clinical outcome.

  7. Discussion • the reported rate of pulmonary embolism has historically been lower Asian populations than in Western populations but newer studies indicate little difference in the frequency • elastic stockings with graduated compression alone is effective in preventing DVTs, thus reducing the frequency of fatal pulmonary embolism. • stockings did not prevent DVT post stroke in CLOTS trial-1 • knee-length stockings are less effective than thigh length in CLOTS trial-2

  8. Discussion • low rates of symptomatic DVT in both groups • may be due either to a decreased awareness of the disease in participating countries • In which less frequent diagnostic testing for suspected events was offered • Or the inclusion in this study of a population that was at lower risk for venous thromboembolism, as compared with other studies • the mean age of the was 9 years younger than the mean age of MEDENOX • BMI was 2 units lower • Proportion of obese patients was 11% Vs 20%. • history of DVT was 10% less in this study

  9. conclusion • among hospitalized, acutely ill medical patients, the rate of death from any cause did not differ significantly between patients who were randomly assigned to pharmacologic prophylaxis with enoxaparin in addition to elastic stockings compared to elastic stockings only • Pharmacologic thromboprophylaxis continues to have proven benefits in preventing DVT, thus reducing the need for the treatment high doses of anticoagulant agents over a prolonged period of time • Which itself can lead to nonfatal but not successfully treated complications such as post thrombotic syndrome or chronic pulmonary HTN.

  10. Strong points • Large number of patients • Multi center • Randomized double blinded • Weak points • Weak discussion • Practice will be the same if there were mortality benefit or not

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