Table 5.
The effects of statins on the prevention of contrast-induced nephropathy: reports from clinical studies
| Study type | Models | Intervention (drug/dose/route/duration) | Major findings | Interpretations | References | |
|---|---|---|---|---|---|---|
| Renal function | Oxidative stress/inflammatory markers | |||||
| Single-center, double-blind randomized placebo-controlled clinical trial |
Age 55–75 years with DM or CKD (Cr > 1.5 mg/dL or GFR 15–60 mL/min/1.73 m2) undergoing elective angiography NAC 1200 mg/po/bid/1 day prior to and until 4 h after angiography treated with nonionic iso-osmolar CM |
Atorvastatin/80 mg/day/po/48 h prior to angiography (n = 110) vs. Placebo (n = 110) |
↓ CIN 24 h after angiography ↔ CIN at 48 h after angiography ↔ Cr |
– | Short-term pretreatment with atorvastatin 80 mg along with high-dose NAC decreased incidence of CIN in high-risk patients undergoing angiography | [66] |
| Prospective, double-blind, randomized, two-arm, parallel group, controlled, clinical trial | Age 18–65 years with Cr 1–1.5 mg/dL or eGFR > 60 mL/min/1.73 m2 and controlled DM or hypertension undergoing CAG |
Atorvastatin/80 mg/po + NAC/1200 mg/po/OD/3 day prior to and 2 day after angiography (n = 80) vs NAC 1200 mg/po/OD 3 day prior to and 2 day after angiography (n = 80) |
Atorvastatin ↓ CIN ↓ mean change in Cr Lesser ↓ eGFR No required dialysis |
– | Short-term high-dose atorvastatin along with NAC was effective in prevention of CIN in high risk patients | [67] |
| Randomized, multicenter, prospective, double-blind clinical trial | Statin-naïve NSTE-ACS undergoing invasive strategy PCI treated with iobitridol | Atorvastatin/80 mg/po/12 h prior to PCI + 40 mg/po/2 h prior to PCI (n = 120) vs. Placebo (n = 121) |
↓ CIN ↓ Cr ↓ CrCl change ↓ hospital stay |
↓ CRP | Short-term pretreatment with high-dose atorvastatin prevented CIN via anti-inflammatory effects, and shortened hospital stay in patients with ACS undergoing PCI | [68] |
| Randomized controlled study | Statin-naïve acute STEMI undergoing emergency PCI treated with non-ionic contrast | Atorvastatin/80 mg/po/prior to PCI (n = 78) vs. Placebo (n = 83) |
↓ CIN ↓ Cr ↓ cystatin C |
– | Short-term pretreatment with high-dose atorvastatin prevented CIN and protected renal function in patients with acute STEMI undergoing emergency PCI | [69] |
| Prospective, randomized trial |
Patients undergoing CAG NAC 600 mg/po/bid/prior to procedure treated with iopamidol |
Atorvastatin/80 mg/po/bid/prior to procedure + 80 mg/po/OD/2 day after procedure (n = 60) vs No atorvastatin (n = 70) |
↔ CIN ↓ Cr ↑ eGFR ↑ Cr change |
– | Short-term atorvastatin protected CIN in patients undergoing CAG | [70] |
| Randomized trial |
CKD (eGFR < 60 mL/min/1.73 m2) scheduled for elective CAG or PCI NAC/1200 mg/po/bid/1 day prior to and day of administration of CM treated with iodixanol |
Atorvastatin/80 mg/po/24 h prior to iodixanol (n = 202) vs No atorvastatin (n = 208) |
↓ CIN ↓ Cr |
– | Single high loading dose of atorvastatin administered 24 h before CM exposure was effective in reducing rate of CIN | [29] |
| Randomized, double-blind, controlled trial | Patients with normal renal function (Cr ≤ 1.5 mg/dL) undergoing elective CTA treated with iopromide | Atorvastatin/80 mg/po/24 h prior to and 48 h after CM (n = 115) vs. Placebo (n = 121) |
↔ CIN ↓ Cr |
– | Short-term treatment with high dose atorvastatin was effective in reduction of Cr level after CM injection in patients undergoing CTA | [71] |
| Randomized trial | Patients undergoing CAG |
Atorvastatin/10 mg/po/24 h prior to procedure (n = 100) vs Atorvastatin/80 mg/po/24 h prior to procedure (n = 50) |
↓ β2M ↓ urine NAG/Cr ↑ CrCl All effects by 80 mg > 10 mg |
– | Short-term pretreatment with high-dose atorvastatin was superior than low dose on attenuating CIN | [72] |
| Randomized trial | STEMI undergoing primary PCI treated with iopromide |
Atorvastatin/80 mg/po/prior to procedure (n = 98) vs Rosuvastatin/40 mg/po/prior to procedure (n = 94) |
↔ CIN ↔ Cr ↔ eGFR ↔ Cr change |
– | Short-term pretreatment with atorvastatin or rosuvastatin had similar efficacy in preventing CIN in patients with STEMI undergoing primary PCI | [114] |
| Prospective, randomized and non-randomized controlled trial | Patients undergoing elective CAG treated with iohexol |
Short-term atorvastatin 40 mg/po/3 day prior to and 2 day after CAG (n = 80) No statin (n = 80) Chronic statin therapy/po/at least 1 mo (n = 80) Atorvastatin/10–40 mg/day/po (n = 57) Simvastatin/10–40 mg/day/po (n = 12) Pravastatin/10–20 mg/day/po (n = 6) Rosuvastatin/10 mg/day/po (n = 3) Fluvastatin/80 mg/day/po (n = 2) |
↓ Cr (atorvastatin and chronic statin therapy) ↑ GFR (atorvastatin and chronic statin therapy) ↓ cystatin C (chronic statin therapy) ↔ Cr, cystatin C and GFR between short term atorvastatin and chronic statin therapy |
– | Short-term and long-term use of atorvastatin had renoprotective effects in low-risk patients undergoing elective CAG | [73] |
| Observational study | ACS undergoing PCI treated with iopamiron |
Simvastatin/40 mg/po/OD/6 months after PCI (n = 128) vs Atorvastatin/20 mg/po/OD/6 months after PCI (n = 143) |
↔ Cr ↔ eGFR |
– | Simvastatin and atorvastatin were similar renoprotective effects for 6 months after PCI | [115] |
| Prospective, audited, multicenter regional registry | Patients undergoing PCI |
Pre-statin/po (n = 10,831) vs No pre-statin (n = 18,040) |
↓ CIN ↓ % of peak Cr ≥ 1.5 mg/dL ↓ nephropathy requiring dialysis |
– | Initiating statin therapy before PCI reduced risk of CIN | [65] |
| Prospective randomized placebo-controlled trial | Patients undergoing CAG treated with iodixanol | Simvastatin/80 mg/day/po/48 h prior to CAG (n = 98) vs. Placebo (n = 96) |
↔ GFR in first 24 h ↓ eGFR reduction after 48 h |
– | Prophylactic administration of simvastatin reduced CIN | [76] |
| Prospective, randomized, controlled, multicenter clinical trial | Age 18–75 years with type 2 DM and CKD stage 2–3 undergoing CAG ± PCI treated with iodixanol | Rosuvastatin/10 mg/po/2 day prior to and up to 3 day after procedure (n = 1498) vs No rosuvastatin (n = 1500) | ↓ CIN | ↓ hsCRP | Short-term rosuvastatin reduced CIN in patients with type 2 DM and CKD undergoing arterial CM injection | [74] |
| Prospective, randomized trial |
Statin-naïve NSTE-ACS patients scheduled for early invasive PCI NAC 1200 mg/po/bid/1 day prior to and 1 day after angiography treated with iodixanol |
Rosuvastatin/40 mg/po/prior PCI + 20 mg/po/after PCI (n = 252) vs No rosuvastatin (n = 252) |
↓ CIN | – | Short-term high-dose rosuvastatin reduced CIN in statin-naïve NSTE-ACS patients undergoing early invasive PCI | [75] |
| Randomized trial | ACS undergoing elective PCI treated with iodixanol |
Simvastatin/20 mg/po/1 day prior to PCI (n = 115) vs Simvastatin/80 mg/po/1 day prior to PCI (n = 113) |
↓ CIN ↓ Cr (80 mg) ↑ CrCl (80 mg) |
↓ hsCRP ↓ P-selectin ↓ intercellular adhesion molecule-1 |
Short-term pretreatment with simvastatin 80 mg before PCI decreased CIN compared with simvastatin 20 mg | [77] |
| Prospective, single-center, randomized, placebo-controlled trial |
CKD (CrCl < 60 mL/min) undergoing elective CAG ± PCI NAC 1200 mg/po/bid/1 day prior to and 1 day after procedure treated with iodixanol |
Atorvastatin/80 mg/po/48 h prior to and 48 h after CM (n = 152) vs. Placebo (n = 152) |
↔ CIN ↔ Cr ↔ persistent kidney injury |
– | Short-term administration of high-dose atorvastatin before and after contrast exposure, in addition to oral NAC, did not decrease CIN occurrence in patients with pre-existing CKD | [79] |
| Prospective, randomized, double-blind, placebo-controlled, 2-center trial | CKD (CrCl ≤ 60 ml/min ± SCr ≥ 1.1 mg/dl) undergoing CAG | Simvastatin/40 mg/po/every 12 h evening prior to up to morning after procedure (n = 124) vs. Placebo (n = 123) |
↔ CIN ↔ Cr ↔ length of hospital stays or 1- and 6-mo |
– | Short-term pretreatment with high-dose simvastatin did not prevent CIN in patients with CKD undergoing CAG | [78] |
| Prospective cohort | CAD ± CKD undergoing CAG |
Atorvastatin/10–40 mg/po (n = 1219) vs Rosuvastatin/5–40 mg/po (n = 635) |
↔ CIN between 2 groups High plasma atorvastatin or rosuvastatin in CIN subgroups |
– | High plasma atorvastatin or rosuvastatin increased risk of CIN | [81] |
| Retrospective study | Age > 18 years undergoing non-emergent PCI |
Statins before PCI (n = 239) Atorvastatin/10–80 mg/po (n = 89) Simvastatin/10–80 mg/po (n = 74) Pravastatin/10–40 mg/po (n = 53) Lovastatin/20–40 mg/po (n = 13) Rosuvastatin/5–20 mg/po (n = 9) Fluvastatin/po (n = 1) No statin before PCI (n = 114) |
↑ CIN | – | Statin use before non-emergent PCI increased incidence of CIN | [80] |
ACS, acute coronary syndrome; β2M, β2-microglobulin; CAD, coronary artery disease; CAG, coronary angiography; CIN, contrast-induced nephropathy; CKD, chronic kidney disease; CM, contrast media; Cr, creatinine; CrCl, creatinine clearance; CRP, C-reactive protein; CTA, computed tomography angiography; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; NAC, N-acetylcysteine; NAG, NAG, N-acetyl-β-glucosaminidase; NSTE-ACS, non-ST-elevated acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction