Remote Postconditioning Reduces AKI in NSTEMI Patients

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In patients with non-ST-segment elevation myocardial infarction (NSTEMI), ischemic conditioning via a series of balloon inflations/deflations during percutaneous coronary intervention (PCI) reduces the risk of acute kidney injury (AKI), according to a randomized study scheduled to be published online March 12, 2013, ahead of print in the Journal of the American College of Cardiology. Treated patients also saw a trend toward improved outcomes at 30 days.

Investigators led by Georgios Giannopoulos, MD, of Athens General Hospital (Athens, Greece), randomized 225 NSTEMI patients at 3 Greek centers to remote ischemic conditioning (n = 113) or sham treatment (n = 112) following revascularization. The postconditioning protocol consisted of 4 cycles of 30 seconds each of balloon inflation and deflation at the lesion site in the culprit vessel. In the similar sham procedure, the balloon was inflated to no more than 3 atmospheres.

Renal Function Protected

The overall incidence of AKI, the primary endpoint, was 21%. Postconditioning reduced the relative risk by 58% compared with controls, yielding an odds ratio of 0.34 (95% CI 0.16-0.71) and a number needed to treat to avoid 1 case of AKI of 6. Postconditioned patients also experienced a smaller decline in estimated glomerular filtration rate (eGFR) and a smaller rise in cystatin C (table 1).

Table 1. Renal Outcomes

 

Conditioning
(n = 113)

No Conditioning
(n = 112)

P Value

AKI

12.4%

29.5%

0.002

Change in eGFR

-8%

-13%

0.009

Change in Cystatin C

4%

19%

< 0.001


At 30 days, Postconditioned patients showed a strong trend toward a lower rate of death or rehospitalization compared with controls (12.4% vs. 22.3%; P = 0.05). Reasons for readmission included acute heart failure, nonspecific chest pain, persistent A-fib, and unstable angina, with more events in the control group for each category.

In multivariate analysis, ischemic postconditioning was an independent predictor of AKI after adjustment for age, BMI, contrast volume, and baseline eGFR (HR 0.23; 95% CI 0.11-0.50; P < 0.001).

According to the authors, 3 main mechanisms have been proposed for how the protective signal is transmitted from the site of postconditioning to the target organ: the neuronal pathway, the release of circulating humoral factors, and activation of a systemic protective effect such as an anti-apoptotic or anti-inflammatory response.

In postconditioning’s favor, Dr. Giannopoulos and colleagues observe, the protocol “involves no additional materials or expenses and presents minimal, if any, technical or logistic challenges.” However, they add, better-powered studies with longer-follow-up are needed to be confident that the strategy does indeed provide clinical benefit and to assess the relative merits of different types of conditioning.

Multiple Unknowns Cloud Research

In a telephone interview with TCTMD, Peter Whittaker, PhD, of Wayne State University (Detroit, MI), said there are multiple possible sources of kidney injury during PCI, from direct toxicity of the contrast agent to ischemia due to microembolization. Fortunately, he noted, postconditioning produces a range of cell-protective effects and appears to have some anticoagulative benefit as well.

However, myriad uncertainties complicate clinical evaluation of the strategy, Dr. Whittaker commented. Not only is the optimal protocol unknown, eg, the number and duration of occlusions, but also the most effective remote site remains unsettled. For example, he noted, typically conditioning is performed on the leg or arm. In theory, the leg may have an advantage since more muscle is conditioned, but the likelihood that CAD patients have coexistent peripheral arterial disease makes the choice problematic. In addition, conditioning in the arm or leg is often performed well before revascularization, which may allow the protective effect to wane.

Then there is the difficulty of translating preclinical results into effective therapy for patients, Dr. Whittaker said, noting that most basic research has been performed in healthy adult animals, while patients who undergo PCI tend to be older and diabetic.

In addition to its biological rationale, Dr. Whittaker said, interest in remote postconditioning has profited from the failure of numerous other measures to protect the kidneys during PCI, with the exception of adequate hydration. At the same time, however, this fact has led many clinicians to become somewhat skeptical about the prospects for any renoprotective therapy, he noted.

Currently, 2 large, randomized trials of remote conditioning—REPAIR, testing the effect on renal function after kidney transplantation, and ERICCA, looking at the impact on MACCE after CABG—are nearing completion, Dr. Whittaker reported. He predicted that results of these studies will strongly influence future pursuit of the strategy.

Study Details

Treated and control groups were well balanced with regard to demographic characteristics and had equivalent preprocedural risk for AKI. In addition, there were no important differences in baseline medications or procedural aspects of the index intervention.

Only nonionic low-osmolar contrast medium was used, and adequate pre- and post-procedural hydration was provided whenever possible. AKI was defined as an absolute rise in serum creatinine of more than 0.5 mg/dL, or a relative increase of more than 25% compared with baseline within 96 hours of PCI.

 


Source:
Deftereos S, Giannopoulos G, Tzalamouras V, et al. Renoprotective effect of remote ischemic postconditioning by intermittent balloon inflations in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2013;Epub ahead of print.

 

 

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Remote Postconditioning Reduces AKI in NSTEMI Patients

In patients with non-ST-segment elevation myocardial infarction (NSTEMI), ischemic conditioning via a series of balloon inflations/deflations during percutaneous coronary intervention (PCI) reduces the risk of acute kidney injury
Disclosures
  • Drs. Giannopoulos and Whittaker report no relevant conflicts of interest.

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