Impact of Atorvastatin Reload on the Prevention of Contrast-Induced Nephropathy in Patients on Chronic Statin Therapy: A Prospective Randomized Trial

Rania Hammami , Omar Masmoudi, Jihen Jdidi, Mouna Turki, Rim Charfi, Imtinene Ben Mrad, Amine Bahloul, Tarek Ellouze, Rania Gargouri, Samir Kammoun, Selma Charfeddine, Fatma Ayedi, Leila Abid



This trial aimed to assess the efficacy of Atorvastatin reloading on the prevention of Contrast-induced nephropathy (CIN) in patients pre-treated with this statin and undergoing coronary catheterization.


This was a prospective randomized controlled study including patients on chronic atorvastatin therapy. We randomly assigned the population to the Atorvastatin Reloading group (AR group), by reloading patients with 80 mg of atorvastatin one day before and three days after the coronary procedure, and the Non-Reloading group (NR group), including patients who received their usual dose without a reloading dose. The primary endpoints were the incidence of cystatin (Cys)-based CIN and Creatinine (Scr)-based CIN. The secondary endpoints consisted of the changes in renal biomarkers (Δ biomarkers) defined as the difference between the follow-up level and the baseline level.


Contrast-induced nephropathy (CIN) is a common complication occurring in 5 to 11% of angiographic procedures [1–4]. The CIN incidence has varied widely across studies as its definition is not the same throughout the literature [5]. CIN is the third leading cause of hospital-acquired acute kidney injury (AKI), accounting for 12% of all cases, next to hypovolemia (42%) and postoperative renal injury (18%) [6]; it accounts for up to 30% of acute kidney injury in hospitalized patients [7]. This complication is strongly associated with significantly increased mortality, extended hospitalization periods, and additional costs [8]. Given the increase in the number of coronary intervention procedures in the last decades and the difficulties to determine CIN mechanisms, many protective measures have been assessed in randomized and observational studies

Material and methods

Study population

This was an interventional prospective, randomized, single-blind, controlled trial, implemented in all consecutive patients (older than 18 years), undergoing coronary angiography or percutaneous coronary intervention in our department between June 2020 and September 2020 and who had already been receiving atorvastatin for at least one week, before admission.

We didn’t include in the present study patients with the following criteria: patients admitted because of an acute coronary syndrome in whom a loading dose is mandatory according to guidelines, statin-naïve patients, patients who received a statin other than atorvastatin before the procedure, patients already receiving 80 mg atorvastatin, patients requiring dialysis and those with eGFR less than 15 ml/min/ 1.73 m2, patients who were exposed to a Contrast Medium (CM) within 7 days, patients with an allergy to contrast media, patients with cardiogenic shock or severe cardiac insufficiency (left ventricular ejection fraction LVEF <20%), patients with severe liver damage, malignant tumor, infectious disease, or fever, and those who refused to consent. We also excluded the patients who didn’t return to get control laboratory tests.


Contrast-induced acute kidney injury (CI-AKI) is a common complication of CM intravascular injection; the physiopathology is complex and not well-understood. Our randomized trial aimed to assess the impact of a reloading dose with 80 mg of atorvastatin on CIN incidence in patients who underwent coronary invasive procedures and who were pre-treated with atorvastatin. The incidence of Scr-based CIN was 10% and the incidence of CYs-based CIN was 31.8% in our trial. In previous studies, the incidence of CYs-CIN ranged between 11 and 28% [20, 23], this is probably due to the high prevalence of diabetes in our population (51%) whereas it was about 30–35% in the other populations.


Four hundred forty-eight patients underwent coronary procedures during the study period. According to inclusion criteria, 120 patients were randomly assigned to the Atorvastatin Reload group (AR group, n = 60) and the Non-reloading group (NR group, n = 60) (Fig 1). However, only 110 patients returned to undergo control laboratory tests; hence, we included only 56 patients in the AR group and 54 patients in the NR group. The number of included patients per day was low, less than one patient per day, given the COVID-19 pandemic, the refusal of certain patients to return for a control test, and the exclusion of acute coronary syndromes from our population. The number of planned coronary catheterization procedures was significantly reduced during this period.


Our study was the first randomized trial in the literature that assessed the beneficial effect of 80 mg atorvastatin reloading on CI-AKI in patients pre-treated with this drug at a lower dose. Our population was at high risk with a high prevalence of cardiovascular factors. We did not find a beneficial effect on the overall population. However, the subgroup analysis showed that this intervention reduces the risk of Cys-based CIN in patients with diabetes type 2. Thus, a short-term reloading regimen of atorvastatin could be advised before coronary catheterization in diabetic patients.

Citation: Hammami R, Masmoudi O, Jdidi J, Turki M, Charfi R, Ben Mrad I, et al. (2023) Impact of atorvastatin reload on the prevention of contrast-induced nephropathy in patients on chronic statin therapy: A prospective randomized trial. PLoS ONE 18(5): e0270000.

Editor: Giuseppe Gargiulo, Federico II University, ITALY

Received: October 3, 2021; Accepted: May 31, 2022; Published: May 8, 2023

Copyright: © 2023 Hammami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.


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