The Effect of Allopurinol on the Risk of Cardiovascular Events in Patients with Cardiovascular Risk

A Randomized, Double-blind, Placebo-controlled Study Evaluating the Effect of Allopurinol on the Risk of Cardiovascular Events in Patients with High and Very High Cardiovascular Risk, Including the Presence of Long-COVID Syndrome.

Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The ALL-VASCOR study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk, excluding ischemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of death.

The ALL-VASCOR study is a randomized, double-blind, placebo-controlled, multi-center trial that examines the effect of allopurinol therapy (200-500mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1,116 patients aged 40-70, with serum uric acid levels above 5mg/dL and with high and very high risk for cardiovascular disease. The ALL-VASCOR study is further designed to assess the occurrence of long-COVID syndrome. The study is directed toward both primary and secondary as well as additional endpoints. Due to the duration of the study, the planned intervention will end on July 31,2028, unless the Safe Monitoring Board or other applicable authorities decide about it. Participant recruitment for the ALL-VASCOR study is set to begin in August of 2023 and will be conducted only within Poland.

Inclusion Criteria:

1. Age: between 40-70 years old.

2. Giving informed consent to participate in the study.

3. Serum UA levels above 5 mg/dl within the last six months before the screening visit.

4. Meeting at least one of the criteria defining high or very high CV risk includes:

   1. calculated 10-year cardiovascular mortality risk based on SCORE2 >2.5% for patients under 50 years old or ≥5% for patients 50 years old or older

   2. documented occurrence of CV diseases (cerebrovascular disease: ischemic stroke, intracerebral bleeding, TIA; heart failure regardless of the etiology NYHA I - II (without IHD), PAD, atrial fibrillation (de novo or ever)

   3. diabetes or arterial hypertension complicated by organ damage:

      • increase in vascular stiffness: pulse pressure ≥ 60 mmHg, and/or cervicofemoral PWV > 10 m/s;
      • features of left ventricular hypertrophy on echocardiography or electrocardiography;
      • increased urine albumin-creatinine ratio (30-300 mg/g);
      • ankle-brachial index < 0.9.

Exclusion Criteria:

1. Taking allopurinol, febuxostat or other hypouricemic drugs.
2. Contraindications to taking allopurinol.
3. Pregnant women, breastfeeding or planning pregnancy during the duration of the study.
4. Hormonal therapy containing oestrogens.
5. Active cancer process or disease in the last five years, excluding locally malignant tumours.
6. Uncontrolled hypertension (mean value ≥ 180/110 mmHg seven days before screening visit) in home measurements despite using hypotensive drugs.
7. 7. Renal insufficiency with an eGFR <45 ml/ min/1.73m2 (according to 2009 CKD-EPI recommendations: stage G3b, G4 and G5).
8. Hypothyroidism or hyperthyroidism not in a state of euthyroidism.
9. Confirmed coronary artery disease (defined as prior AMI, revascularization of the myocardium, confirmed presence of atherosclerotic plaques in coronary arteries on imaging studies).
10. Heart failure in NYHA class III and IV.
11. Taking preparations: azathioprine, mercaptopurine or cyclosporin. Participation in another clinical trial of a medicinal product or medical device within the last three months or five half-lives, whichever period is longer.