Rivera M, Tamariz L, Suarez M, Contreras G: Modifying Effect of Statins on Fatal Outcomes in Chronic Kidney Disease Patients in the Systolic Blood Pressure Intervention Trial: A Post Hoc Analysis. Am J Nephrol 2019;49:297–306
Both blood pressure control (with antihypertensive agents) and lowering low density lipoprotein (LDL) cholesterol levels (with statins) are widely regarded as cornerstones of prevention of cardiovascular disease (CVD) related morbidity and mortality in patients with non-dialysis requiring CKD, as shown by the SPRINT and SHARP trials. The interaction of these two interventions on outcomes has not been well studied.
Rivera and colleagues conducted a post-hoc analysis of the SPRINT data in order to examine the impact on fatal outcomes and CVD events of combinations of statin use and low blood pressure targets in 2646 subjects with CKD (1343 taking statins and 1273 not taking statins, 19 unknown). Quite remarkably, the hazard ratio (HR) CVD mortality was dramatically decreased in patients taking a statin and assigned to the intensive blood pressure lowering group (fully adjusted HR= 0.29). No such reduction of CVD mortality risk was seen in the non-statin group.
As this is a post-hoc analysis, a causal interpretation of these findings is not possible (as emphasized in an accompanying Editorial by Tu and Agarwal). Nevertheless, this interaction raises important issues concerning the combined use of statins and low blood pressure targets in prevention of mortality (and morbidity) from CVD in patients with non-dialysis requiring CVD. For example, how robust is the interaction as the severity of CVD worsens? What are the optimal goals for both blood pressure and LDL cholesterol to achieve optimum outcomes? Is the interaction seen to the same degree in diabetic and non-diabetic subjects?
It is also of interest to note that neither intervention may have an equivalent impact on the rate of progression of chronic kidney disease (CKD) to end-stage kidney disease (ESKD). Most older patients with progressive CKD die of CVD before reaching ESRD. Therefore the net population effect will be to reduce mortality for CVD and paradoxically increase the incidence rate of treatment requiring ESRD. Certainly, extended patient survival is a laudable and desirable outcome, but unless progression of CKD can be halted or slowed, the overall impact of combined statin and lower blood pressure targets may be to increase, not decrease the societal burden of ESRD and its treatment. What is needed is an interventional strategy that both retards CKD progression and reduces CVD morbidity and mortality, simultaneously.