Cardiovascular disease is the leading cause of death and morbidity in patients with chronic kidney disease (CKD), making measures to improve cardiovascular outcome a clinical priority.1 Nevertheless, there are various uncertainties with the use of standard cardiovascular therapy to this subpopulation, due to the routine exclusion of patients with underlying CKD in many cardiac interventions trials.1 At the conference of Advances in Medicine (AIM) hosted by the Chinese University of Hong Kong (CUHK) , Prof. Carol Pollock from the University of Sydney presented recent advances in the cardioprotective strategies in CKD patients.
The presence of kidney dysfunction affects the cardiovascular system in multiple ways, including accelerated progression of atherosclerosis and exacerbation of congestive heart failure (CHF).2 In this meeting, evidence-based recommendations for therapeutic strategies in two subpopulations, i.e. acute coronary syndrome (ACS) and CHF, were discussed.
Prof. Pollock pointed out there has been a risk-treatment paradox in the management of ACS, in which patients with CKD, especially those with estimated glomerular filtration rate (eGFR) stage 3-5, are less likely to receive invasive coronary procedures due to the fear of precipitating acute kidney injury (AKI), even though a graded relationship between decreasing renal function and increasing risk of cardiovascular death or myocardial infarction was previously reported.3,4
“In contrast to our current belief, propensity score-matched analysis showed that early invasive management was not associated with a significant increase in the risks of clinically relevant renal outcomes, including the short-term risk of AKI requiring dialysis or the long-term risk of end-stage renal diseases (ESRD), when compared to conservative treatment. Meanwhile, ~20% relative reduction in mortality was consistently observed across varying levels of baseline eGFR in those with early invasive management. These findings support an argument that patients with mild, moderate, and severe CKD may benefit from invasive therapy when the risk/benefit ratio is favorable,” Prof. Pollock said.
While current evidence does not offer definitive guidance to the use of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with CKD, Prof. Pollock suggested that a preference of CABG over PCI may exist in view of the better survival outcome and 3-year major adverse cardiac and cerebrovascular event rate with CABG in a population-based study.5 Noting that the prevalence of clopidogrel resistance is higher in those with CKD than in the general population,2 “ticagrelor and perhaps prasugrel, rather than clopidogrel, should be considered,” she said.
In the context of CHF, there remains a debate regarding the omission of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in patients with advanced CKD. Prof. Pollock noted that several publications may have hinted at the possibility of ACEi/ARB in accelerating the progression of CKD. Indeed, an observational report from Ahmed A et al. has demonstrated significant and sustained improvements in kidney function over 12 months among older adults with stage 4/5 CKD, following the withdrawal of angiotensin inhibition (eGFR at baseline, 16.38 ± 1mL/min/1.73m2; at month 12, 26.6 ± 2.2mL/min/1.73m2; p=0.0001), which delayed the onset of renal replacement in the majority of those studied.6 Similarly, therapeutic interventions with 50% reduction in basal angiotensin inhibition was found to improve kidney function (eGFR 42.9mL/min/1.73m2 vs. 32.5mL/min/1.73m2), and survival outcomes at 6 and 12 months (86.7% vs. 75% and 69.3% vs. 50%, respectively) when compared to standard dose of ACEi/ARB.7
“These data may justify a rethink of our approach to the inhibition of the renin-angiotensin-aldosterone system (RAAS) in patients with advanced CKD. However, it is still uncertain whether the potential gain in eGFR with ACEi/ARB cessation outweigh the potential adverse cardiovascular outcomes. It is hoped that STOP ACEi, which is a large randomized trial currently ongoing in the UK, will provide answer to this question,“ Prof. Pollock said.
Over the last 2-3 years, progress have been made in discovering novel agents (e.g. serelaxin, omecamtiv mecarbil) or re-tasking known medications (e.g. SGLT2 inhibitors and metformin), to offer potential renal and cardiovascular benefits concomitantly in CKD patients. It is anticipated that the treatment landscape may continue to evolve as our understanding to the pathophysiology of cardiorenal disease deepens.