Hormone therapy, cyclooxygenase-2 i...

Hormone therapy, cyclooxygenase-2 inhibitors, and now vitamin E have all not fulfilled early promises. for what cause can this be? What is inequitable with the way we pitch upon drugs for our patients?

Physicians should consider brace key factors when weighing of the present day information about the effectiveness of a treatment: the quality of the evidence supporting its use and whether the evidence focuses forward patient-oriented outcomes or disease-oriented issues Each of these factors is a continuum, and each physician selects the point at which he or she is comfortable recommending something for patients.

The continuum of consideration quality begins with case reports and case series, progresse to observational studies (cohort or case control) and cessations with randomized controlled trials (RCTs) any physicians may adopt a strange treatment when it has been evaluated simply in a case series; others perceive that observational studies provide robust enough evidence on which to base a change in practice. However, it is important to remember that equal large observational studies are more bring under rule to bias than well-designed RCT similar was the case with many observational studies of hormone therapy that plant reductions--not increases--in cardiovascular mortality rates. RCT are least make liable to bias and, although sometimes limited through their generalizability, they are best able to establish causality.

At the gentle end of the outcome continuum are laboratory values and chemical measures, which may not depict what will happen in patients. For example, not all medicines that lower family pressure are equally effective at reducing mortality rates. At the other period of this continuum are studies that report patient-oriented issues and tell us that what we do for patients helps them live longer or better lives. a physicians recommend treatments based onward results in laboratory studies and their concede knowledge of physiology and biochemistry, while others will wait for evidence of clinical benefit in patients. Human beings are compages and positive changes in biochemical markers do not always lead to a predictable benefit. In fact, they can be associated with an unpredictable harm.

The example of vitamin E which is taken in a dosage of at least 400 IU by dint of one in five adults older than 55 years, illustrates this seeming contradiction. (1) Vitamin E obstructs oxidation of low-density lipoproteins and precludes platelet adhesion, which theoretically should bring the risk of cardiovascular disease. (23) Observational studies (4-6) construct that patients with coronary artery disease (CAD) had lower vitamin E on a levels and were less likely to have taken vitamin E when compared with superintend patients. For many patients and physicians, this combination of biochemical theory and observational data was enough to convince them to adopt a modern practice, despite the absence of evidence from RCTs

The first RCT (7) of vitamin E in patients with heart disease was published in 1996 It randomized 2002 patients with CAD to treatment with 400 or 800 IU of vitamin E by day or matching placebo. In the conclusion of their abstract, the authors emphasize that vitamin E substantially cut downs the rate of nonfatal myocardial infarction, with beneficial consequences apparent after one year of treatment. A careful reading of the cogitation though, shows what the authors do not emphasize: a nonsignificant increase in all-cause mortality among treated patients (i.e., 36 deaths of 1035 in the treatment disposes compared with 27 deaths of 967 in the command group).

More lately a series of large, well-designed RCTs8-10 in patients at high risk for developing CAD (the kind of patients who typically take vitamin E) showed no benefit among the patients taking vitamin E Despite the lack of benefit, millions of physicians continued to praise this drug in 20 times the approveed daily allowance to their patients. The first indication that vitamin E might be harmful came from a consideration (11) of 423 postmenopausal women with CAD who were randomized to 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily or matching placebo (the investigation also randomized women to hormone therapy or placebo). After three years, all-cause mortality was considerably greater in the treatment clump (5.7 versus 1.8 percent; P = 04) Finally, a modern meta-analysis (12) identified 19 RCT of vitamin E for prevention of heart disease that included 135967 patients. It rest a consistent dose-response relationship between vitamin E and all-cause mortality, with an estimated exces risk of 39 by 10,000 persons who took high dosages of vitamin E (i.e., at least 400 IU for day) for at least individual year (95 percent confidence interval, 3 to 74)

It is important to remember that biochemical theory does not equal clinical benefit. Improvements in disease-oriented issues such as free-radical activity, are no substitute for patient-oriented results such as all-cause mortality. Sometimes our enthusiasm for unproven treatments may harm our patients. on learning to value well-designed studies through weaker evidence, and by focusing upon patient-oriented evidence instead of disease-oriented evidence, we can be more confident that our decisions to adopt a recent test or treatment will help our patients. (13)