In the general population, a meta analysis of the Physicians’ Health Study I and II (healthy male physicians, aged 40–84 years) and Women’s Health Study (healthy female physicians aged >45 years) showed that there was no significant reduction in SCD in participants taking aspirin for primary prevention (91 SCD/61947, HR = 0.78, 95% CI = 0.52–1.18).[19] The event rate was selleck products small. Aspirin-prescribing habits in haemodialysis patients vary widely in different countries, from 8% in Japan to 41% in Australia and New Zealand. In observational studies, this was associated with no increase in gastrointestinal bleeds.[20] There should be future RCTs to validate whether aspirin is effective in preventing SCD in haemodialysis

patients. High aldosterone levels are reported to be an independent risk factor for SCD in non-dialysis CKD; an increase of 50 pg/mL of aldosterone was associated with an adjusted HR of 1.32 (P < 0.001, 95% CI = 1.15–1.52).[21] In an analysis BIBW2992 supplier of randomized trials utilizing ACEIs in patients without renal disease and post-myocardial infarction, ACEI was associated

with a reduction in SCD (OR = 0.80, 95% CI = 0.70–0.92).[22] The proposed mechanisms include blood pressure reduction, inhibition of neuro-humoral activation and regression of LVH.[22] No equivalent RCT data exist for CKD-5D. To date, RCTs have been undertaken which primarily explore the effect of ACEI on cardiovascular mortality and events, rather than SCD specifically. In the Fosinopril in Dialysis Mirabegron Trial (FOSIDIAL), 397 haemodialysis patients were randomized to fosinopril or placebo. After a 2 year follow-up, there was no reduction in cardiovascular events (RR = 0.929; 95% CI = 0.68–1.26) with fosinopril.[23] After adjustments for risk factors, there was a trend towards benefit in the treatment arm (adjusted RR = 0.79, 95% CI 0.59–1.1, P = 0.099), but like so many studies in dialysis patients, this one was underpowered. A further small open-label RCT[24] investigated the effect of candesartan (4–8 mg/day) versus placebo in 80 haemodialysis patients without cardiomyopathy. After a median follow-up of 19.4 ± 1.2

months, there were more cardiovascular events and increased mortality in the control group versus the treatment group (cardiovascular events: 45.9% vs 16.3%, and mortality: 18.9% vs 0.0%, P =< 0.01). There were only three SCD in the control group and none in the treatment group.[24] The study was therefore inconclusive on the effects of candesartan on SCD. Nevertheless, a sound theoretical basis exists for potential benefits of renin-angiotensin blockade in CKD-5D. Further studies are required to test these hypotheses. In the general population, the Randomised Aldactone Evaluation Study (RALES Study) randomized 1663 patients with LVEF <35%, including 792 with CKD who had baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 cm2, to spironolactone or placebo.