Please select the eligibility criteria that correspond to the clinical trial below.
Title: Platelet Function in Diabetic Patients With and Without Renal Impairment, and the Effects of Lipid Lowering Treatment
Brief Summary: The purpose of this study is compare the effects of simvastatin+ezetimibe with those of simvastatin alone on platelet activity, platelet-leukocyte interactions and inflammatory variables in diabetic patients with or without impaired renal function.


Options:
A: Inclusion Criteria:

* age \>16 years
* hypertension, defined as a systolic or diastolic blood pressure \> 140 or 90 mmHg respectively (or less in patients with concomitant antihypertensive therapy)
* creatinine clearance \>20 ml/min/1.73m2 (with variation of less than 30% in the 3 months prior to study entry)
* urinary protein excretion rate persistently \> 1 g/24 hours (average of at least two measurements in two urine collections two weeks apart) without evidence of urinary tract infection or overt heart failure (New York Heart Association class III or more)
* written informed consent

Exclusion criteria:

* specific contraindication to statin therapy because of a previous coronary event or serum LDL-cholesterol levels \> 190 mg/dL despite a low cholesterol (\<200 mg/day) diet and a saturated fatty acid in take less than 7% of total calories will not be included
* chronic treatment with corticosteroids, nonsteroidal anti-inflammatory drugs, or immunosuppressive drugs
* acute myocardial infarction or cerebrovascular accident in the six months preceding the study - severe uncontrolled hypertension (diastolic blood pressure \>115 and/or systolic blood pressure \>220 mmHg)
* evidence or suspicion of renovascular disease, obstructive uropathy, type 1 diabetes mellitus, vasculitides, cancer
* elevated serum aminotransferase concentrations - chronic cough
* history of poor tolerance or allergy to ACEi, ATA or statins
* drug or alcohol abuse
* pregnancy, breast feeding and ineffective contraception
* legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial.
B: Inclusion Criteria:

Patients must have a documented history of at least one of the following:

* Hypertension (defined as systolic blood pressure 140 mmHg or a diastolic blood pressure 90 mmHg (defined as the disapperance of all sound \[Korotkoff Phase V\] or receiving anti-hypertensive treatment. Blood pressure should be measured after sitting the patient quietly for 3 minutes).
* Retinopathy (defined as any of the following; non-proliferative retinopathy, pre-pre-proliferative retinopathy, proliferative retinopathy, maculopathy, advanced diabetic eye disease or history of photocoagulation).
* Microalbuminuria (defined as either, Albumin creatinine ratio \> than = to 2.5 mg/mmol, or Albumin excretion rate on a timed collection \> than = to 20 mcg/min (\> than = to 30 mg/24hrs) on two successive occasions, or a positive micral or other strip test).
* Macroalbuminuria (defined as either; Albustix or other dipstick evidence of gross proteinuria, Albumin creatinine ratio \> than = to 25 mg/mmol; or Albumin excretion rate on a timed collection \> than = 200 mcg/min (\> than = 300 mg/24hrs) on two sucessive occasions).
* Current smoker

Exclusion Criteria:

* Type I Diabetes Mellitus
* Any major Coronary event prior to entry into the study
C: Inclusion Criteria:

* History of chronic kidney disease (CKD): either patients who are pre-dialysis (with a plasma or serum creatinine greater than or equal to 150 micromol/l \[greater than or equal to 1.7 mg/dl\] in men, or greater than or equal to 130 micromol/l \[greater than or equal to 1.5 mg/dl\] in women); or patients on dialysis (hemodialysis or peritoneal dialysis)
* Men or women aged greater than or equal to 40 years

Exclusion Criteria:

* Definite history of myocardial infarction or coronary revascularization procedure
* Functioning renal transplant, or living donor-related transplant planned
* Less than 2 months since presentation as an acute uraemic emergency (but could be entered later, if appropriate)
* Definite history of chronic liver disease, or abnormal liver function (i.e. alanine aminotransferase \[ALT\] greater than 1.5 x upper limit of normal \[ULN\] or, if ALT not available, aspartate aminotransferase \[AST\] greater than 1.5 x ULN). (Note: Patients with a history of hepatitis were eligible provided these limits were not exceeded.)
* Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) greater than 3 x ULN
* Definite previous adverse reaction to a statin or to ezetimibe
* Concurrent treatment with a contraindicated drug. (Note: Patients who were temporarily taking such drugs could have been re-screened for participation in the study when they discontinued them, if appropriate.) These contraindicated drugs included: HMG-CoA reductase inhibitor ("statin"); fibric acid derivative ("fibrate"); nicotinic acid; macrolide antibiotic (erythromycin, clarithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease-inhibitors (e.g. antiretroviral drugs for HIV infection); nefazodone; ciclosporin
* Child-bearing potential (i.e. premenopausal woman who was not using a reliable method of contraception)
* Known to be poorly compliant with clinic visits or prescribed medication
* Medical history that might have limited the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer other than non-melanoma skin cancer, or recent history of alcohol or substance misuse)
D: Inclusion Criteria:

* Diabetes mellitus type 1 or type 2
* With or without established microalbuminuria (albumin-to-creatinine ratio (ACR)2,5-25 mg/mmol for men, and 3,5-25 mg/mmol for women, according to ISH and ESC recommended criteria)
* Glomerular filtration rate (GFR) between 15-60 ml/min/1.73m2 (measured the last 6 months) or GFR \>75ml/min/1.73m2. The abbreviated Modification of Diet in Renal Disease (MDRD) equation will be used to calculate GFR.
* Age 18-80 years

Exclusion Criteria:

* Definite history of myocardial infarction, coronary revascularisation procedure or stroke. (i.e, a strong clinical indication for statin treatment)
* Functioning renal transplant, or living donor-related transplant planned.
* Patients on dialysis.
* Poor metabolic control, i.e HbA1c \> 9%
* Definite history of chronic liver disease, or abnormal liver function (i.e ALT \>1,5 x ULN or, if ALT not available, AST \> 1,5 x ULN).
* Evidence of active inflammatory muscle disease (e.g dermatomyositis, polymyositis), or CK\>3 x ULN;
* Definite previous adverse reaction to a statin or to ezetimibe
* Definite previous adverse reaction to acetylsalicylic acid.
* Definite previous adverse reaction to an ACE-inhibitor.
* Need for concomitant treatment with a strong inhibitor of CYP3A4, such as itrokonazole, ketokonazole, erythromycin, clarithromycin, HIV-protease inhibitors or nefazodone (i.e. agents that may markedly elevate simvastatin levels).

Answer: D