Effect of Aliskiren on Arterial Stiffness and Platelet Function in Patients With Type 2 Diabetes Mellitus, a Comparison With Losartan
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 主要终点
- arterial stiffness and platelet function
研究概览
简要总结
Aliskiren is a novel renin inhibitor approved for the treatment of hypertension. The effect of aliskiren on arterial stiffness, inflammation and oxidative stress has not been fully investigated yet.The aim of this study is to investigate the effect of aliskiren on arterial stiffness, platelet function and inflammation compared to losatan in patients with diabetes mellitus.
We hypothesize that aliskiren will have a beneficial effect on arterial stiffness and platelet function in patients with diabetes mellitus.
详细描述
Background:
Patients with diabetes mellitus (DM) have an increased risk for atherothrombotic events.
Platelets play an important role in cardiovascular disease both in the pathogenesis of atherosclerosis and in the development of acute thrombotic events. Their importance in coronary heart disease is indirectly confirmed by the benefit of antiplatelet agents in these disorders. Platelet adhesion, aggregation and activation are abnormal in patients with DM. Several factors were found to be associated with the abnormalities in platelet signaling in patients with DM, including increased levels of reactive oxygen species, altered calcium mobilization and increased protein tyrosine phosphorylation.
Arterial stiffness, assessed noninvasively by measuring the aortic pulse wave velocity (PWV), is considered a powerful and independent risk factor for early mortality. Increased arterial stiffness may lead to early pulse wave reflection causing an increase in systolic blood pressure and a decrease in diastolic blood pressure. This in turn, increases the myocardial oxygen demand, reduces ejection fraction and increases the left ventricular working load. PWV probably represents an integrated index of vascular structure and function, being influenced by many factors including age, blood pressure, lipid profile and glucose levels. For any level of systolic blood pressure, aortic PWV is found to be increased in diabetic patients compared to nondiabetic patients.
Aliskiren is the first direct renin inhibitor that was introduced for the treatment of hypertension. Aliskiren binds to the active site of renin, inhibiting the activation of the renin- angiotensin- aldosteron (RAAS) system at the rate limiting step. Aliskiren inhibits the conversion of angiotensinogen to angiotensin I (AI). This direct inhibition may be more efficient than the indirect blockade of ACE inhibitors or ARBs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The study will include 40 patients aged 18 years or older with DM, defined as patients with fasting plasma glucose above 126 mg/dL or
- •symptoms of DM with random blood glucose concentration of above 200 mg/dL, or
- •patients treated with oral hypoglycemics or insulin.
- •In addition, prior to their enrollment in the study patients' BP will be assessed by 24 hour ambulatory BP monitoring.
- •All patients will have to be treated with ACE inhibitors, aspirin and statins for at least one month prior to their enrollment in the study.
- •Patients' medication regimen will not be altered during the study period.
- •Patients will sign a written informed consent before their inclusion in the study.
排除标准
- •Patients will be excluded from the study if their systolic BP is between bellow 110 mmHg or above 150 mmHg mmHg.
- •Major exclusion criteria will be:
- •acute coronary syndrome in the 6 months previous to the study,
- •renal failure with creatinin levels above 1.5 mg/dL,
- •hyperkalemia (K > 5 mg/dL),
- •hematologic or solid malignancies,
- •pregnancy
- •a platelet count below 100,000.
研究组 & 干预措施
1
Patients with diabetes melittus treated with an ACE inhibitor will be treated with aliskiren
干预措施: aliskiren (Drug)
1
Patients with diabetes melittus treated with an ACE inhibitor will be treated with aliskiren
干预措施: losartan (Drug)
2
Patients with diabetes melittus treated with an ACE inhibitor will be given losartan
干预措施: aliskiren (Drug)
2
Patients with diabetes melittus treated with an ACE inhibitor will be given losartan
干预措施: losartan (Drug)
结局指标
主要结局
arterial stiffness and platelet function
时间窗: 6.5 months
次要结局
- oxidative stress parameters (oxidized LDL and Isoprostanes), markers of inflammatory status (highly sensitive CRP test) and 24 hours blood pressure monitoring(6.5 months)