Medication prescription to improve outcomes in advanced chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a major public health issue affecting 10% of the global population and resulting in 1.2 million deaths. The risk of all-cause and cardiovascular mortality is inversely proportional to declining eGFR such that individuals with CKD are more likely to die, primarily due to a cardiovascular cause, than survive to the point of requiring dialysis. These poor outcomes are related to a myriad of factors including multimorbidity, medial vascular calcification and underlying haemostatic dysfunction.

Polypharmacy is a key consequence of the disease burden experienced by CKD patients. It is linked with poor adherence, adverse drug reactions, falls and increased hospitalisations. A post-hoc analysis of the CKD-FIX study was conducted to assess the prevalence and predictors of polypharmacy in CKD patients. It found that polypharmacy, defined as ≥5 medications, and hyperpolypharmacy, defined as ≥10 medications, were found in 77.5% and 34.3% of patients respectively. Age ≥65 yrs, diabetes, cardiovascular disease and hyperlipidemia were independently associated with polypharmacy.

However, limiting polypharmacy via appropriate prescribing is hampered by the lack of data in patients with advanced CKD. Despite the disproportionate cardiovascular disease burden in CKD, the benefits and risks of dual antiplatelet therapy are not known. Therefore a systematic review of randomised controlled trials on the effectiveness of dual antiplatelet therapy in CKD was conducted. Nineteen trials with 27,308 participants were analysed with all but 3 trials excluding participants with dialysis-dependent kidney failure. Compared with aspirin monotherapy or no study medication, P2Y12 inhibitor-based dual antiplatelet therapy significantly reduced the risks of major adverse cardiovascular events, myocardial infarction and stroke; but increased the risk of major bleeding. There was insufficient evidence to conclude whether patients with advanced stages of CKD and dialysis-dependent kidney failure derived benefit.

In conclusion, CKD patients represent an expanding population that is at high risk of adverse outcomes. Polypharmacy is common in patients with CKD and is related to age and multimorbidity. Further research on medication appropriateness and deprescribing are needed. In particular, adequately powered randomized trials are required to evaluate the effectiveness of dual antiplatelet therapy in patients with advanced stages of CKD and cardiovascular disease.