Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk.

Ju-Chi Liu,Szu-Yuan Wu,Yi-Ping Hsu,Giuseppe Remuzzi

doi:10.1371/journal.pone.0162588

Abstract

BackgroundTaiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin–angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients.MethodsOf 248,797 patients who received a hypertension diagnosis in Taiwan during 2001–2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose–response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28–90, 91–365, and >365 cumulative defined daily doses (cDDDs).ResultsIn the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50–0.65), 0.72 (0.53–0.98), and 0.47 (0.41–0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54–0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used.ConclusionStatins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

Highlights

In Taiwan, 92.4% of patients with renal diseases undergo hemodialysis; this percentage is 91.7% in the United States and 18.7% in Hong Kong [1]
Significant differences were observed among the four groups in the distributions of age; sex; monthly income; urbanization level; and use of nonstatin lipid-lowering drugs, aspirin, renin–angiotensin system inhibitor (RASI), and metformin (Table 1)
The combined use of RASIs and statins might have the highest potential for reducing dialysis risk, as indicated by the RASI + statin group having the lowest adjusted hazard ratios (aHRs) among all groups

Summary

Introduction

In Taiwan, 92.4% of patients with renal diseases undergo hemodialysis; this percentage is 91.7% in the United States and 18.7% in Hong Kong [1]. Taiwan has the highest incidence and prevalence of renal diseases and dialysis use worldwide [3]. Hypertension is common in acute vascular diseases, such as vasculitis and scleroderma renal crisis. In these settings, blood pressure increases because of ischemia-induced renin–angiotensin system activation, rather than volume expansion [8]. Inhibiting angiotensin II formation with an ACEI is effective in patients with vasculitis or scleroderma renal crisis [9]. No clear evidence indicating that early RASI use reduces dialysis risk in hypertensive patients without CKD has been reported. We evaluated the association of statin and renin–angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients

Methods

Results

Conclusion