Effect of statin therapy on contrast-induced nephropathy after coronary angiography: A meta-analysis

https://doi.org/10.1016/j.ijcard.2011.05.045Get rights and content

Abstract

Background

Although the pleiotropic effects of statins are postulated to be renoprotective, clinical studies have demonstrated conflicting results. We undertook a meta-analysis of published trials to evaluate the impact of statin therapy on the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography.

Methods

We searched MEDLINE and EMBASE databases through December 2010 for articles evaluating the effect of statins on the incidence of CIN in patients undergoing coronary angiography. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using random effects modeling.

Results

Three randomized controlled trials involving 770 patients (330 in the statin group and 340 in the control group) and 7 non-randomized studies involving 31,959 patients (11,936 statin-pretreated and 20,023 statin-naïve). The definition of CIN varied somewhat among the studies. Based on the pooled estimate across the 3 randomized controlled trials, statin therapy did not significantly reduce the incidence of CIN compared to control (OR = 0.76, 95% CI: 0.41–1.41, p = 0.39). No significant heterogeneity was found in the randomized studies (I2 = 0%, p = 0.48). The pooled analysis of the non-randomized studies showed a marginally significant benefit associated with statin therapy (OR = 0.60, 95% CI: 0.36–1.00, p = 0.05). There was significant heterogeneity among the non-randomized studies (I2 = 88%, p < 0.00001).

Conclusions

Our meta-analysis suggests that statin therapy might be associated with a significant reduction in the incidence of CIN in patients undergoing coronary angiography. Further studies are warranted to clarify this issue.

Introduction

Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography with a frequency ranging between 5% and 50% depending on the baseline characteristics of the patient population. The highest incidence occurs in those with severe renal dysfunction, diabetes, congestive heart failure, advanced age, and concurrent administration of nephrotoxic drugs [1], [2]. CIN is the third leading cause of hospital-acquired acute renal failure, accounting for 12% of all cases [3]. Moreover, the development of CIN is associated with increased morbidity and mortality, length of hospitalization, and chronic renal impairment [4], [5].

The pathophysiology of CIN is multi-factorial, complex, and not well understood. Some of the mechanisms of injury that have been described include renal vasoconstriction causing medullary ischemic damage, tubular injury leading to production of oxygen free radicals, decrease in nitrous oxide production, and direct nephrotoxicity [6].

Several strategies to prevent CIN have been studied and these include the use of: theophylline, fenoldopam, mannitol, iloprost, furosemide, dopamine, hemofiltration, ascorbic acid, and N-acetylcysteine (NAC). However, a meta-analysis of trials evaluating the aforementioned agents suggested no benefit in preventing CIN [7]. Moreover, a meta-analysis consisting of 13 randomized trials evaluating the use of NAC prior to coronary angiography concluded that the data was inconclusive, yet NAC is the most widely used preventative strategy [8]. A recent randomized, multi-center trial assessed the use of iso-osmolar versus low osmolar contrast in the prevention of CIN, and concluded that there was no difference between the two agents [9]. Moreover, the optimal hydration strategy either with sodium bicarbonate solution or normal saline also remains controversial in preventing CIN [10], [11].

More recently, several trials have been published on the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in preventing CIN, which yielded inconsistent results [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Apart from the cholesterol-lowering effects, statins have been shown to exhibit the following pleiotropic effects that might target the factors that lead to CIN: scavenge free oxygen radicals (anti-oxidant), increase nitrous oxide production, and enhance vascular smooth muscle relaxation [23].

Although the pleiotropic effects of statins are postulated to be renoprotective, clinical studies have demonstrated conflicting results. In order to summarize the cumulative data to-date, and thereby improve estimation power and precision through the increased sample size of the cumulative data, we conducted a meta-analysis of published studies to evaluate the impact of statin therapy on the incidence of CIN.

Section snippets

Literature search

We searched MEDLINE (1966 to December 2010), EMBASE (1947 to December 2010), and the Cochrane Library databases for articles evaluating the effect of statin therapy on the incidence of CIN in patients undergoing coronary angiography. Using the terms contrast-induced nephropathy, statins, contrast, contrast media, cardiac catheterization, and coronary angiography, we searched for articles indexed as randomized or non-randomized trials. We also searched published abstracts presented at the

Eligible studies

The electronic database searches identified 184 potentially relevant articles. After independently reviewing the title and abstract of all potential articles, 12 articles were retrieved and reviewed in full-text. Of these, one study which evaluated the effect of statin therapy on renal function in patients undergoing elective coronary angiography was excluded because it did not provide data on the incidence of CIN [22]. Another study was excluded because it compared two different doses of a

Discussion

This meta-analysis of the currently available published data suggests that statin therapy might be associated with a significant reduction in the incidence of CIN in patients undergoing coronary angiography. Moreover, our analysis suggests that statin therapy, even when administered acutely prior to coronary angiography may prevent CIN. This finding is extremely important because of the availability and low cost associated with this preventative approach. However, it should be acknowledged that

Conclusion

This is the first meta-analysis that consolidates the available information to-date regarding the use of statins in the prevention of CIN after coronary angiography. Although statin therapy had an overall trend towards a beneficial effect among the analyzed studies, caution is advised when interpreting these data because of the non-randomized nature of most of the studies and the significant heterogeneity among the studies. Clinical equipoise remains for the performance of a large randomized

Acknowledgement

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [37].

References (37)

  • J.L. Zhao et al.

    Effect of statins on contrast-induced nephropathy in patients with acute myocardial infarction treated with primary angioplasty

    Int J Cardiol

    (2008)
  • A.R. Jadad et al.

    Assessing the quality of reports of randomized clinical trials: is blinding necessary?

    Control Clin Trials

    (1996)
  • R. DerSimonian et al.

    Meta-analysis in clinical trials

    Control Clin Trials

    (1986)
  • J. Xinwei et al.

    Comparison of usefulness of simvastatin 20 mg versus 80 mg in preventing contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention

    Am J Cardiol

    (2009)
  • G. Patti et al.

    Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial

    J Am Coll Cardiol

    (2007)
  • L. Shewan et al.

    Ethics in the authorship and publishing of scientific articles

    Int J Cardiol

    (2010)
  • S.K. Morcos et al.

    Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR)

    Eur Radiol

    (1999)
  • S.J. Schwab et al.

    Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent

    N Engl J Med

    (1989)
  • Cited by (55)

    • Comparison of Transradial and Transfemoral Approaches for Coronary Angiography and Percutaneous Intervention in Patients with Coronary Bypass Grafts

      2020, Cardiovascular Revascularization Medicine
      Citation Excerpt :

      A well-established adverse side effect of the contrast media used during catheterization is kidney injury. Previous studies were able to associate an increased incidence of contrast induced nephropathy (CIN) with the increased amount of contrast used during procedures [16]. Furthermore, studies have shown that this phenomenon can be potentiated in those with preexisting renal dysfunction, thus introducing even greater potential for CIN following catheterization [17–19].

    View all citing articles on Scopus
    View full text