Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Aspirin on Renal Disease Progression in Patients With Type 2 Diabetes: a Multicentre Double-blind, Placebo-controlled, Randomised Trial. The LEDA (renaL disEase Progression by Aspirin in Diabetic pAtients) Study.
Brief Summary: The pathophysiology of diabetes is multifactorial. Beyond genetic susceptibility loci, a lot of acquired risk factors are involved in the development and progression of the disease. Chronic complications of diabetes can be divided into vascular and nonvascular. The risk of developing complications increases with the duration of hyperglycemia, and usually become apparent in the second decade of hyperglycemia. Vascular complications are further subdivided into microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, peripheral arterial disease, cerebrovascular disease). It is estimated that the annual decline of estimated glomerular filtration rate (eGFR) in diabetic adults is about 2.1-2.7 ml/min.

While there is consolidated evidence about the use of aspirin (ASA) for secondary prevention in diabetic patients, there is no consensus on the use in primary prevention; the use of ASA in these patients is at physician discretion.

ASA is an effective antithrombotic agent that inhibits the production of thromboxane (Tx) A2 and other prostaglandins by blocking cyclooxygenase (COX). In patients treated with aspirin, serum TxB₂ level is the most reliable in vivo indicator of COX-1 inhibition than TxA2, due to its short half-life and artifacts associated with platelet activation ex vivo.

COX are present in the kidney in the macula densa, in the medulla and in the interstitium. Experimental animals models have demonstrated that COX are involved in regulation of renal blood flow. In particular, in a murine animal model, after the administration of COX inhibitors such as aspirin and celecoxib, it was observed an improvement in renal plasma flow and eGFR, suggesting a role for Tx in the progression of renal damage However, data on the relationship between aspirin and renal function in humans are scarce. In a recent work lead on a large cohort of 800 patients with non-valvular atrial fibrillation, ASA use was associated with a reduced progression of eGFR \<45 ml/min during 2 years of follow-up. Furthermore, basal levels of urinary excretion of TxB2, correlated inversely with the use of aspirin and with the decrease of eGFR at follow-up.

The aim of the study is to evaluate the decline in renal function in diabetic patients treated with low-dose aspirin (100 mg/day) vs. untreated diabetic patients.


Options:
A: Inclusion Criteria:

* symptomatic CAD (including acute coronary syndrome) or positive stress test and a native coronary lesion (\>50% diameter stenosis by visual estimation on coronary angiogram and reference diameter \> 2.5 mm)
* AND CKD or DM patients

Exclusion Criteria:

* if they had contraindication to aspirin, clopidogrel or sarpogrelate.
B: Inclusion Criteria:

* Diagnosis of type 2 diabetes: random blood glucose ≥ 200 mg / dl, fasting blood glucose ≥ 126 mg/dl, blood glucose 2 hours after oral glucose tolerance test (75 g) ≥200 mg/dl, treatment with glucose-lowering agents.

Exclusion Criteria:

1. History of cardiovascular or cerebrovascular events;
2. Presence of inadequate glycaemic control (glycosylated haemoglobin ≥8%);
3. Clinical diagnosis of type 1 diabetes (diagnosis of diabetes and insulin use before 35 years of age);
4. Patients with renal impairment in G4 stage (eGFR \<30 ml/min) at baseline;
5. Chronic active infection or evidence of malignancy in the last 5 years;
6. Autoimmune systemic disease;
7. Cardiac arrhythmia;
8. Use of non-steroidal anti-inflammatory drugs, vitamin supplements, or other antiplatelet agents in the previous 30 days;
9. Liver Failure (eg cirrhosis);
10. Use of anticoagulants;
11. Life expectancy \<1 year;
12. Known allergy to aspirin.
C: Key Inclusion Criteria:

* Male and female
* Age of 50 years or older
* Permanent, paroxysmal, or persistent atrial fibrillation (at screening or within 6 months prior to enrollment) documented by 12-lead electrocardiogram)
* At least 1 of the following risk factors for stroke:

  * Prior stroke or transient ischemic attack
  * Age of 75 years or older
  * Arterial hypertension on treatment
  * Diabetes mellitus
  * Heart failure (New York Health Authority Class 2 or greater at time of enrollment)
  * Left ventricular ejection fraction of 35% or less, documented within 6 months of enrollment
  * Peripheral arterial disease (previous arterial revascularization, limb or foot amputation, or current intermittent claudication with ankle-arm systolic blood pressure ratio \<0.9)
* Not currently receiving vitamin K antagonist therapy for 1 of the following reasons:

  * Previous vitamin K antagonist therapy demonstrated as unsuitable and discontinued
  * Vitamin K antagonist therapy not previously used but expected unsuitable

Key Exclusion Criteria:

* Women who are pregnant or breast feeding
* Women of child bearing potential who are unwilling to meet the study requirements for pregnancy testing or are unwilling or unable to use an acceptable method to avoid pregnancy
* Atrial fibrillation due to reversible causes, such as thyrotoxicosis or pericarditis
* Valvular disease requiring surgery
* Planned ablation procedure for atrial fibrillation to be performed within 3 months
* Conditions other than atrial fibrillation that require chronic anticoagulation (such as, prosthetic mechanical heart valve, venous thromboembolism)
* Patients with serious bleeding in the last 6 months or at high risk for bleeding, including but not limited to those with:

  * Active peptic ulcer disease
  * Platelet count \<100,000/mm\^3 or hemoglobin \<10g/dL
  * Recent stroke (within 10 days)
  * Documented hemorrhagic tendencies or blood dyscrasias
* Current alcohol or drug abuse or psychosocial reasons that make study participation impractical
* Severe comorbid condition with life expectancy \<1 year
* Severe renal insufficiency; any patient with a serum creatinine level \>2.5 mg/dL or a calculated creatinine clearance \<25 mL/min is excluded
* Alanine transaminase or aspartate aminotransferase levels \>2 times upper limit of normal (ULN) or a total bilirubin level \>1.5 times ULN (unless an alternative causative factor \[such as Gilbert's syndrome\] is identified)
* Allergy or adverse reaction to acetylsalicylic acid
* Required treatment with a thienopyridine (clopidogrel or ticlopidine)
* Prisoners or participants who are compulsory detained (involuntarily incarcerated)
* Use of an investigational drug or device within the past 30 days or prior randomization into an apixaban clinical study
* Patients who are compulsorily detained for treatment for a psychiatric or physical illness
D: Inclusion Criteria:

1. Are undergoing noncardiac surgery;
2. Are ≥ 45 years of age;
3. Are expected to require at least an overnight hospital admission after surgery; AND
4. Fulfill one or more of the following 5 criteria:

   * History of coronary artery disease
   * History of peripheral vascular disease
   * History of stroke
   * Undergoing major vascular surgery
   * Any 3 of the following 9 criteria:

     * undergoing major surgery (i.e. intraperitoneal, intrathoracic, retroperitoneal or major orthopedic surgery
     * history of congestive heart failure
     * transient ischemic attack
     * diabetes and currently taking an oral hypoglycemic agent or insulin
     * age ≥ 70 years
     * hypertension
     * serum creatinine \> 175 µmol/L (\> 2.0 mg/dL)
     * history of smoking within 2 years of surgery
     * undergoing urgent/emergent surgery

Exclusion Criteria:

1. Consumption of ASA within 72 hours prior to surgery
2. Hypersensitivity or known allergy to ASA or clonidine
3. Systolic blood pressure \< 105 mm Hg
4. Heart rate \< 55 beats per minute in a patient who does not have a permanent pacemaker
5. Second or third degree heart block without a permanent pacemaker
6. Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks
7. Intracranial hemorrhage documented by neuro-imaging, in the 6 months prior to randomization. This does not include petechial hemorrhagic transformation of a primary ischemic stroke
8. Subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months prior to randomization and the offending aneurysm or arterial lesion has been repaired
9. Drug-eluting coronary stent in the year prior to randomization
10. Bare-metal coronary stent in the 6 weeks prior to randomization
11. Thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel) or ticagrelor within 72 hours prior to surgery; or intent to restart a thienopyridine or ticagrelor during the first 7 days post-op; or currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine;
12. Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent
13. Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
14. Not consenting to participate in POISE-2 prior to surgery
15. Previously enrolled in POISE-2 Trial

Answer: B