The Impact of Iso-Osmolar Contrast Use in Emergent Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

Abstract: The incidence of contrast-induced nephropathy (CIN) in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) was previously reported to be as high as 19%. Iso-osmolar contrast has frequently been used for populations at high risk for CIN, but a recent meta-analysis did not show a significant benefit of using iso-osmolar contrast in preventing CIN. The aim of our study is to evaluate the impact of iso-osmolar contrast use in patients undergoing emergent PCI. We performed a retrospective analysis of patients who underwent primary and rescue PCI for STEMI. The PCI strategy, including the contrast choice, was left at the discretion of the operator. CIN was defined as an increase in creatinine of more than 0.5 mg or 25% from the baseline within 72 hours. Among 212 patients, CIN was seen in 33 patients (16%). Patients who received iso-osmolar contrast were older, and included more patients at risk for CIN. The incidence of CIN was 14% in the low-osmolar contrast group and 17% in the iso-osmolar contrast group (P=.799). After logistic regression analysis, CIN was seen more frequently in patients who had lower ejection fraction, post-PCI TIMI flow <3, and lower hemoglobin. The use of iso-osmolar contrast was not associated with a lower incidence of CIN in patients undergoing emergent PCI for STEMI.

J INVASIVE CARDIOL 2011;23(11):448-450

Key words: ST-segment elevation myocardial infarction, primary percutaneous coronary intervention, contrast-induced nephropathy, iso-osmolar contrast

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Contrast-induced nephropathy (CIN) is a relatively common complication of cardiac catheterization and percutaneous coronary intervention (PCI). It is associated with short-term and long-term adverse clinical outcomes, and its incidence has been reported to vary from 2-20% depending on the population.^1-3 The major risk factors for CIN include underlying renal insufficiency (creatinine >1.5 mg/dL), diabetic nephropathy, and heart failure.³ The incidence of CIN is higher in patients with acute myocardial infarction because of the frequent presence of hemodynamic instability and the lack of time for pre-hydration. In a previous study, the incidence of CIN was 19% in patients who underwent primary PCI for ST-segment elevation myocardial infarction (STEMI).¹ Iso-osmolar contrast (iodixanol) initially showed a lower incidence of CIN compared to low-osmolar contrast, but a recent meta-analysis did not support this finding.^4,5

The aim of this study was to compare the incidence of CIN with the use of iso-osmolar contrast versus low-osmolar contrast in patients who underwent emergent PCI for STEMI.

Materials and Methods

Study population. All patients who underwent primary PCI or rescue PCI for failed thrombolysis for acute STEMI at our institution from March 2004 until September 2009 were eligible for this study. Medical records were retrospectively reviewed and clinical, angiographic, and laboratory data were collected. Patients who had end-stage renal disease on hemodialysis, patients who did not undergo PCI, and patients whose creatinine values were not available daily for 72 hours post-procedure were excluded.

Procedures. PCI was performed in the standard fashion. Aspirin 325 mg was given before the PCI, unfractionated heparin was given to maintain the activated clotting time over 250 seconds, and a loading dose of clopidogrel (300 mg or 600 mg) was given before or after the PCI. Glycoprotein IIb/IIIa inhibitor was given at the discretion of the operator. Choice of contrast and hydration protocol were left to the discretion of the operator. Post-PCI hydration was determined based on the patient’s clinical condition, including left ventricular function, left ventricular end-diastolic pressure, renal function, and volume of contrast used. In general, if the patient was not in congestive heart failure, a normal saline infusion was continued for 12 hours. Contrasts were classified into iso-osmolar contrast (iodixanol; Visipaque^®; n = 121) and low-osmolar contrast (iopromide [Ultravist^®; n = 53], iopamidol [Isovue^®; n = 28], and iohexol [Omnipaque^®; n = 10]).

Endpoints. CIN was defined either as an increase in creatinine >0.5 mg within 72 hours or as an increase in creatinine >25% from the baseline within 72 hours.⁶ Major adverse cardiac events (MACE) were defined as death, myocardial infarction, and target vascular revascularization (TVR). In-hospital MACE and length of stay were compared between the two groups.

CIN risk score. The CIN risk score was calculated as described earlier by Mehran et al.³ The CIN risk score consists of the following factors: use of intra-aortic balloon pump (IABP), hypotension, congestive heart failure, age >75 years, anemia, diabetes mellitus, contrast volume, and baseline renal function.

Statistical analysis. Continuous variables are expressed as mean ± standard deviation and discrete variables are presented as percentages. Clinical characteristics of the patients who received iso-osmolar contrast and low-osmolar contrast were compared. Multiple regression analysis with backward elimination was conducted to assess multivariate predictors of CIN. The following variables were entered in a multiple regression analysis model after univariate analysis: age, gender, history of diabetes mellitus, baseline creatinine, baseline hemoglobin, left ventricular ejection fraction, post-PCI TIMI-3 flow, intra-aortic balloon pump use, and type of contrast. The c-index was 0.75 for this model. Categorical variables were analyzed using the Chi-Square test or Fisher’s test.  Continuous variables whose distribution met normality assumptions were analyzed using the t-test. Variables whose distribution did not meet normality assumptions were analyzed using the non-parametric Wilcoxon rank-sum test. All tests were two-tailed, and P-values of <.05 were considered significant.

Results

Among 212 patients who underwent emergent PCI, CIN was seen in 33 patients (16%). Among 33 patients who developed CIN, a creatinine increase >0.5 mg/dL was seen in 5 patients and a creatinine increase >25% was seen in 28 patients. None of the patients required hemodialysis after PCI.  Overall, mean age was 59.6 years old, 29.7% had diabetes mellitus, and 5.2% had a baseline Cre >1.5 mg/dL. Patients who received iso-osmolar contrast were older, had a higher prevalence of baseline renal insufficiency and anemia (although the laboratory values were not available at the time of the selection of the contrast) (Table 1), and required intra-aortic balloon pump more frequently (Table 2). The CIN risk score was higher in patients who received iso-osmolar contrast (4.1 ± 3.3 vs 6.8 ± 5.3, P<.001)

The incidence of CIN was 14% in the low-osmolar contrast group and 17% in the iso-osmolar contrast group (P=.799). There was no significant difference in the incidence of CIN between the two groups.

The incidence of CIN was significantly higher in patients who had lower left ventricular ejection fraction (LVEF) (40 ± 14% vs 45 ± 13%, P=.049), post-PCI TIMI flow <3 (39% vs 16%, P=.002), or required the use of an intra-aortic balloon pump (30% vs 13%, P=.003) (Table 3). After logistic regression analysis, lower LVEF (OR, 0.967; 95% CI, 0.937-0.998; P=.040), lower hemoglobin (OR, 0.792; 95% CI, 0.647-0.969; P=.024), and post-PCI TIMI flow <3 (OR, 0.345; 95% CI, 0.149-0.802; P=.013) were independent predictors for CIN. The use of iso-osmolar contrast was not associated with decreased incidence of CIN (OR, 0.842; 95% CI, 0.394-1.800; P=.842).

In-hospital major adverse cardiac events (MACE) were seen in 6 patients (5%) in the iso-osmolar contrast group (3 deaths, 1 acute myocardial infarction, 2 target vessel revascularizations [TVR]) and 2 patients (2%) in the low-osmolar contrast group (2 TVR, P=.471). Patients who developed CIN had higher in-hospital MACE (12% vs 2%, P=.021) and death (9% vs 0%, P=.003) than patients who did not develop CIN. Length of stay was 9.4 ± 10.2 days in the CIN group vs 6.9 ± 6.9 days in the no-CIN group (P=.08).  

Discussion

In our retrospective analysis, iso-osmolar contrast had no impact on the incidence of CIN compared to low-osmolar contrast. In an earlier trial that compared the iso-osmolar contrast iodixanol and the low-osmolar contrast iohexol in 129 high-risk patients with diabetes and chronic kidney disease who underwent angiography, iodixanol was associated with a lower incidence of CIN.⁴ However, a recent meta-analysis did not show an overall benefit of iso-osmolar contrast in the prevention of CIN in coronary angiography.⁵ Its substudy showed that among the different pharmacologic types of low-osmolar contrast, iodixanol did significantly decrease the incidence of CIN when compared to ioxaglate and iohexol. In our study, the most common types of low-osmolar contrast used were iopromide and iopamidol, which had similar incidences of CIN to iso-osmolar contrast in previous studies. A recent large observational study with propensity matching demonstrated that iso-osmolar contrast was used more frequently in higher-risk patients, but the adjusted risk of CIN was not different among patients who received iso-osmolar contrast and low-osmolar contrast,⁷ which is similar to our finding.

There are several strategies in the prevention of CIN. The effects of sodium bicarbonate and acetylcysteine have been evaluated in multiple studies, but there is significant heterogeneity among the existing trials. Prophylactic hydration and minimization of total contrast volume remain the most beneficial treatments to prevent CIN. The effect of isotonic saline in preventing CIN has been well shown in previous studies,⁸ and it can be achieved with low cost. However, in patients who need emergent coronary angiography and PCI, hydration may not be possible since these patients will not have sufficient time for hydration. These patients also are more likely to present with congestive heart failure, which limits the use of hydration. Intravenous acetylcysteine infusion and sodium bicarbonate may have additional benefit in this setting.^9,10

In previous studies, the incidence of CIN in patients undergoing emergent PCI was 11.5-19%, and age >75 years, anterior wall myocardial infarction, time-to-perfusion, contrast volume >300 mL, and IABP were associated with a higher incidence of CIN.^1,11 In our study, lower LVEF and post-PCI TIMI <3 were the independent variables associated with the incidence of CIN. Interestingly, our study demonstrated the association of unsuccessful PCI (TIMI flow <3) with the incidence of CIN. This result, along with the predicting variables from previous studies, suggests that in patients with STEMI, the clinical condition of the patient appears to be a more important predictor of CIN than the underlying patient risk factors.

Study limitations. First, this was a retrospective analysis, and patients were not randomized to low-osmolar and iso-osmolar contrast. The patients who received iso-osmolar contrast were at a higher risk for CIN. In addition, with the small sample size, this study does not have power to predict the difference between the two groups. Second, intravenous acetylcysteine and sodium bicarbonate were not used. Though it is not standard practice, some studies have shown a benefit from these approaches, and it may have impacted the incidence of CIN in our cohort. Third, the definition of CIN we used in this study is an increase in creatinine >0.5 mg within 72 hours or an increase in creatinine >25% from the baseline within 72 hours. This is the most common definition of CIN; however, it may over-diagnose the deterioration of kidney function. Our study is of value since there are limited data evaluating the choice of contrast in the setting of emergency PCI. However, due to its retrospective design, it remains only hypothesis-generating. It is imperative that further prospective, randomized studies should be conducted to compare the incidence of CIN with the use of iso-olmolar contrast and low-osmolar contrast in the setting of STEMI.

Conclusions

In our retrospective study, iso-osmolar contrast did not affect the incidence of CIN. The incidence of CIN was independently associated with lower LVEF, postprocedure TIMI flow <3, and lower hemoglobin.

References

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8. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regiments in 1620 patients undergoing coronary angioplasty. Arch Intern Med. 2002;162(3):329-336.
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From Beth Israel Medical Center, New York, New York.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted May 26, 2011, provisional acceptance given July 6, 2011, final version accepted August 10, 2011.
Address for correspondence: Dr. Yumiko Kanei, Beth Israel Medical Center, Cardiology, 1st Avenue at 16th Street, New York, NY 10003. Email: yumikanei@hotmail.com