September 26, 2002
Warfarin, Aspirin, or Both after Myocardial Infarction
Antithrombotic therapy is routinely prescribed after myocardial infarction. This study compared the effect of warfarin, aspirin, or the combination of both medications on a composite end point of death, nonfatal reinfarction, or thromboembolic stroke. Both warfarin regimens were superior to the aspirin regimen. The combined-therapy regimen was somewhat more favorable than the warfarin-alone regimen but not significantly so. Aspirin is the most commonly used antithrombotic drug after myocardial infarction, but this study suggests that warfarin or warfarin plus aspirin may be more effective in reducing coronary events. However, the risk of bleeding episodes was higher with the warfarin regimens, a fact that must be considered in clinical decision making.
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Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C
Interferon-based therapies combined with ribavirin are effective for chronic hepatitis C, but many patients do not have a response and side effects are common. Pegylated interferons are more efficacious than standard interferons. In this large trial, peginterferon alfa-2a plus ribavirin resulted in a higher rate of sustained virologic response (56 percent) than interferon alfa-2b plus ribavirin (44 percent) and peginterferon alfa-2a alone (29 percent). Side effects occurred less often with peginterferon alfa-2a plus ribavirin than with interferon alfa-2b plus ribavirin. Peginterferon alfa-2a plus ribavirin appears to be better treatment than interferon alfa-2b plus ribavirin for chronic hepatitis C, because the regimen containing pegylated interferon is more effective with fewer side effects.
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Nephrolithiasis and Osteoporosis with Hypophosphatemia Caused by Mutations in the Type 2a Sodium–Phosphate Cotransporter
Familial aggregation occurs among persons with renal calcium stones or bone demineralization, suggesting a genetic propensity toward these disorders. In this study of 14 patients with stones and 6 with bone demineralization, all of whom also had hypophosphatemia and decreased renal phosphate reabsorption, 2 patients were found to have unique mutations in the type 2a sodium–phosphate cotransporter. Considering additional phenotypic features in persons with common clinical conditions can aid in selecting candidate genes in which mutations may explain the clinical abnormalities.
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Special Article: An Economic Evaluation of Activated Protein C Treatment for Severe Sepsis
Recombinant human activated protein C has been shown to reduce mortality among patients with severe sepsis. Given the high cost of activated protein C ($6,800 per therapeutic course) and the high incidence of severe sepsis, the economic implications of widespread use of activated protein C are important. In this cost-effectiveness analysis, the authors report that activated protein C is associated with a cost of about $28,000 per year of life gained and $47,000 per quality-adjusted year of life gained. However, treatment of patients with an APACHE II score of 24 or less is associated with a cost of $575,000 per year of life gained. When used in patients with severe sepsis and greater severity of illness (an APACHE II score of 25 or more), activated protein C is associated with favorable cost-effectiveness ratios. It is not clear that treatment of patients with an APACHE II score of 24 or less is economically justifiable.
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Clinical Practice: Raynaud's Phenomenon
A 37-year-old woman reports that her fingers turn blue when they are exposed to the cold and that she has fatigue, arthralgias, and a history of small, painful digital ulcers. How should she be evaluated and treated? This article reviews the evaluation and treatment of patients with Raynaud's phenomenon.
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Clinical Implications of Basic Research: COX Inhibitors and Thromboregulation
Prostacyclin inhibits platelets and dilates blood vessels, whereas thromboxane A2 activates platelets and constricts vessels. In mice lacking receptors for prostacyclin, intimal injury provokes a severe reaction within the artery, whereas in mice lacking thromboxane A2 receptors the response is subdued. These findings are relevant to clinical concerns that cyclooxygenase-2 inhibitors, which specifically impair the formation of prostacyclin, may increase susceptibility to cardiovascular events. Aspirin, which inhibits both prostacyclin and thromboxane A2, protects against arterial thrombosis.
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