New PRESERVE Analysis Backs Normal Saline Hydration in PCI

Patrice Wendling

May 03, 2018

Neither intravenous (IV) sodium bicarbonate nor oral N-acetylcysteine (NAC) were superior to IV saline in reducing 90-day adverse events or contrast-associated acute kidney injury (AKI) in patients who underwent percutaneous coronary intervention (PCI), results of a PRESERVE substudy show.

"It's a well-defined clinical trial that probably will settle the issue of whether this intervention should be used or not," Santiago Garcia, MD, University of Minnesota and Minneapolis VA Healthcare System, told | Medscape Cardiology.

Contrast-associated AKI affects 7% of patients undergoing PCI in the United States and is associated with increased risk for morbidity and a 10-fold increase in 30-day mortality.

Last year, PRESERVE showed no benefit of IV sodium bicarbonate over IV sodium chloride or of oral NAC over placebo for the prevention of death, need for dialysis, or an increase of at least 50% in serum creatinine at 90 days among nearly 5000 patients with chronic kidney disease undergoing coronary angiography (4.4% vs 4.7%; 4.6% vs 4.5%).

The results were described at the time as "quite stunning" and likely to "immediately impact" clinical practice, but subsequent editorials challenged their generalizability to patients undergoing PCI because of the higher amounts of contrast medium used.

Indeed, median contrast volume was more than double in the 1161 patients with PCI vs the 3304 patients without PCI (160 mL vs 75 mL; P < .01), although IV fluids administered before, during, and after angiography were higher for patients undergoing PCI.

When investigators zeroed in on the PCI group, however, there was no benefit once again with regard to the primary outcome for sodium bicarbonate over normal saline (2.64% vs 4.04%; odds ratio [OR], 0.64; 95% CI, 0.33 - 1.24) or for NAC over placebo (3.84% vs 2.84%; OR, 1.37; 95% CI, 0.71 - 2.62).

Contrast-associated nephropathy also was not significantly different between the groups (OR, 0.93; 95% CI, 0.65 - 1.34; OR, 0.98; 95% CI, 0.69 - 1.41, respectively), according to the late-breaking presentation at the Society for Cardiovascular Angiography and Interventions (SCAI) 2018 Scientific Sessions.

Results for both outcomes were consistent in subgroup analyses, including estimated glomerular filtration rate, diabetes, urine albumin-to-creatinine ratio, contrast volume, and study site.

"We certainly achieved what we wanted to achieve, which was to try to enrich this population with patients who have been exposed to higher amounts of contrast medium and patients who have higher risk of contrast-induced nephropathy, which in the main trial was 8% and in this trial was 11% or about 30% higher," Garcia said. "So I think we can say that even in this high-risk cohort this intervention seemed to be effective."

Results of smaller clinical trials and meta-analyses of the various interventions have produced mixed results. Many cath labs have moved to isotonic sodium chloride to prevent adverse renal outcomes, but clinical practice is "all over the place," he said.

Wiggle Room or Wishy-Washy?

Current SCAI guidelines endorse the administration of sodium chloride and a move away from sodium bicarbonate and do not recommend NAC. The American College of Cardiology/American Heart Association PCI guidelines are a bit more "wishy-washy," recommending IV hydration but without specifying which fluid should be given, Garcia said.

"The guidelines should probably be more specific about recommending normal saline after all this evidence," he added.

Asked to comment, session co-moderator H. Vernon Anderson, MD, University of Texas Medical Center, Houston, said via email, "The current guidelines do not endorse any specific fluid, which I do agree with. Flexibility is a good thing here."

He observed that standard of care for angiography procedures does require some attention to hydration to protect renal function, which means that risk stratification for renal injury should be undertaken.

"The weight of the evidence, including the PRESERVE study, is that normal saline solution is the default hydration agent unless there are other extenuating circumstances," he said. "So far, no other agent or agents has been shown to be superior to normal saline."

Fellow session co-moderator George Dangas, MD, PhD, Mount Sinai Medical Center, New York City, told | Medscape Cardiology via email, "This study supports the existing totality of evidence that routine administration of anything else is not superior to simple normal saline hydration" but that "individualized practices may still apply in high-risk individuals or procedures."

These may include, for example, the use of sodium bicarbonate when it is specifically indicated, one-half normal saline in patients with significant sodium-dependent hypertension or congestive heart failure, or acetylcysteine in patients with very high risk for renal failure.

In coronary heart procedures, the assessment of left ventricular end-diastolic pressure or pulmonary capillary wedge pressure as a guide to the hydration level intra- and postprocedure also can be important criteria, particularly in patients who may not tolerate a volume overload state, and the routine preoperative hydration may be risky, he noted.

"No randomized study thus far has had enough patients in these rather rare conditions to allow clear evidence-based consensus," Dangas said. "The use of systematic risk stratification may allow developing different routine strategies in intermediate- or high-risk cases in the future."

PRESERVE excluded patients who urgently needed to go to the cath lab in less than 3 hours, which may limit generalizability of its findings to very high-risk patients, such as those with ST-segment elevation MI or cardiogenic shock, Garcia and colleagues note.

"We certainly want to proceed with caution in those patients, but if anything, with all the complexities of bicarbonate, these are not the ideal patients to be treated with that type of fluid because you have to premix this and it takes time to get it to the patient," he said in the interview. "So if anything, saline would mitigate some of these complexities and make the therapy available to patients sooner rather than later."

PRESERVE randomly assigned patients to receive IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and 1200 mg twice-daily NAC or placebo capsules. The administration of IV fluids was protocolized with dose/timing/rate ranges: 3 to 12 mL/kg prior to angiography, 1 to 1.5 mL/kg/hour during angiography/PCI, and 1 to 3 mL/kg/hour after angiography. 

Enrollment was stopped early after a preplanned interim analysis revealed a lack of significant differences in the groups for the primary outcome.

In addition to the exclusion of very high-risk patients, other limitations are the predominantly male cohort and limited power of the substudy based on the small number of patients; however, overall results are consistent with the parent trial, Garcia said.

The trial was funded by the VA Cooperative Studies Program and the National Health and Medical Research Council of Australia. Garcia reported grant support from Edwards Lifescienes and consulting fees from Medtronic, Boston Scientific, Osprey Medical, and Surmodics.

Society for Cardiovascular Angiography and Interventions (SCAI) 2018 Scientific Sessions. Presented April 26, 2018.

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