Risk-benefit profile clinical trials

Clinical trials and meta-analyses have demonstrated that early carotid endarterectomy (CEA) is the preferred treatment for most patients with severe symptomatic internal carotid artery (ICA) stenosis and selected patients with moderate disease.However, CEA is often delayed in chnical practice, or may not be appropriate in some patients due to an unfavorable risk-benefit profile. In these settings, it is reasonable to consider acute antithrombotic treatment to prevent early recurrent stroke. 

Niacin can raise uric acid levels, and in diabetics can raise blood glucose levels. However, several clinical trials have shown that niacin can be used safely and effectively in patients with diabetes.33 Due to the high cardiovascular risk of patients with diabetes, the benefits of improving the lipid profile appear to outweigh any adjustment in diabetic medication(s) that is needed.33... 

The recent trends toward the use of lower doses of aspirin have been driven by the belief that these offer a better safety profile while retaining equivalent therapeutic efficacy. Despite the large number of patients enrolled in randomized clinical trials and included in meta-analyses, there is no firm evidence that dose reduction significantly lowers the risk of gastrointestinal bleeding. Patients and doctors therefore need to consider the trade-off between the benefits and harms of long-term treatment with aspirin. Meanwhile, it seems wise to use the lowest dose of proven efficacy. 

Therapeutic confirmatory (Phase III) Demonstrate/confirm efficacy Establish safety profile Provide an adequate basis for assessing the benefit/risk relationship to support licensing Establish dose-response relationship Adequate and well controlled studies to establish efficacy Randomized parallel dose-response studies Clinical safety studies Studies of mortality/morbidity outcomes Large simple trials Comparative studies... 

In addition to its antihypertensive effects, the ARB losartan demonstrated cardiovascular benefits beyond lowering blood pressure in the Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study [8]. Similarly, results from the Valsartan in Acute Myocardial Infarction Trial showed that valsartan improves survival after acute MI in high-risk patients [15]. Due to a lack of clinical studies involving populations with the same cardiovascular risk profile, it is not possible to extrapolate these findings to all ARBs, particularly since the dose of ARB used appears critically important [7]. Several ARBs carry additional indications, including treatment of hypertension with LVH, stroke prevention, CHF, and nephropathy in typ. 2 diabetes mellitus. 

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