NSTEMI Patients With CKD: Early Invasive vs Delayed Strategy Similar for Survival

Observational data from Israel show no benefit from angiography within 24 hours, but also no harm.

NSTEMI Patients With CKD: Early Invasive vs Delayed Strategy Similar for Survival

The likelihood that a patient with moderate or severe chronic kidney disease (CKD) will survive following an NSTEMI does not differ based on whether they undergo coronary angiography within 24 hours or at a later time, observational data from Israel indicate.

Researchers led by Amir Sharon, MD (Chaim Sheba Medical Center, Tel Hashomer, Israel), say their results call into question current US and European guidelines, which emphasize an early invasive strategy in the first 24 hours.

Elad Maor, MD, PhD (Chaim Sheba Medical Center), the study’s senior author, told TCTMD these guidelines were in fact what motivated them to conduct the study. Specific to NSTEMI patients with CKD, “there is no data, generally speaking,” he said, “because these patients are usually systematically excluded from randomized clinical trials.”

Moreover, the issue of how best to manage patients with these dual conditions is becoming ever more relevant given that CKD is expected to grow in prevalence and is already seen in 40% of NSTEMI patients, Maor pointed out. Theirs is a single-center report, he acknowledged, but it provides useful information to address knowledge gaps, since randomized clinical trials dedicated to this are unlikely.

The paper was published today in JACC: Cardiovascular Interventions.

What their results suggest is not that delayed angiography is preferred, said Maor. Rather, “I would say it’s safe to wait. There’s no need to rush. There is no need to run to the cath lab with a patient with advanced kidney disease. You can take time. Sometimes we give fluid to hydrate the kidneys. You might consider transferring the patient to a better facility [if needed].”

Carlo Briguori, MD, PhD (Mediterranea Cardiocentro, Naples, Italy), and Giuseppina Roscigno, PhD (Mediterranea Cardiocentro and Percuros, Leiden, the Netherlands), writing in an editorial, point out these data now extend the same lesson offered by ISCHEMIA-CKD, conducted in stable CAD: that “no advantages exist” for an early invasive approach in patients with advanced CKD.

“At present, awaiting randomized clinical trials on this topic, only patients with NSTEMI and mild (stage II) and moderate (stage IIIa) CKD may benefit from an early invasive strategy,” the editorialists specify.

It’s safe to wait. There’s no need to rush. There is no need to run to the cath lab with a patient with advanced kidney disease. Elad Maor

Sripal Bangalore, MD (NYU Langone Health, New York, NY), ISCHEMIA-CKD’s principal investigator, highlighted that both studies explore whether there’s a heterogeneity of treatment effect based on kidney function. “Even though [the current analysis] is not definitive, it again points to the same thing: that patients with advanced CKD may behave slightly differently than patients who have no kidney disease or less-severe forms of kidney disease,” he commented to TCTMD.

Bangalore, who co-authored the 2021 US revascularization guidelines, pointed out that, apart from the timing aspect, the writing group gave a class 2a recommendation to angiography and revascularization in NSTEMI patients with CKD and “high-risk features.”

“As a clinician, what I struggle with is twofold. One is, there is a real concept of ‘renalism.’ Cardiologists will look at kidney function, even though we are no experts at kidney function, and withhold all of the therapies that are lifesaving,” he noted, adding, “And then there is this issue of trying to balance: what to do with patients with advanced kidney disease, given that the randomized trials are not there? So because of that . . . the guidelines the way they’re stated I think [offer] flexibility.”

With the right expertise, such as using zero-contrast PCI, the risks to patients with advanced CKD can be lowered, such that “hopefully you can drive the same benefit [as in] patients without kidney disease,” said Bangalore.

Indeed, he added, the Israeli data suggest that at least there doesn’t appear to be any signal of increased harm among the patients with moderate/severe CKD: “We have to individualize care—in appropriate patients, in the appropriate settings, and with the appropriate expertise, we should be able to do these procedures safely.”

Even Split in Use of Both Strategies

Sharon et al took a retrospective look at 7,107 consecutive NSTEMI patients treated at Chaim Sheba Medical Center, Israel’s largest hospital, between 2008 and 2021. They focused on the 3,529 who were invasively treated (median age 66 years; 77% male). Around half (52%) underwent coronary angiography within 24 hours and the rest did so at a later time, with median delays between NSTEMI diagnosis and angiography of 15 and 45 hours, respectively.

At-least moderate CKD, defined as an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2, was present in 14% of the invasively treated group.

Within 30 days, the patients with moderate/severe CKD had higher mortality than those who did not (4.0% vs 0.5%), though there was no interaction between kidney disease and angiography timing. Over a median follow-up of 4 years, mortality rates reached 42% for patients with moderate or worse CKD, compared with 11% for those with no or less-severe CKD.

Since the choice to use an early invasive strategy was not randomized, the researchers then used inverse probability treatment weighting to reduce the likelihood of confounding by indication and selection bias. “We used a strong statistical method that confirmed the validity of our findings,” said Maor.

With this adjustment, early angiography was associated with lower mortality versus a delayed strategy overall for the NSTEMI patients. Yet there was an interplay between strategy and outcome (P for interaction < 0.001), such that only patients with eGFR ≥ 60 (HR 0.70; 95% CI 0.56-0.85) and those with eGFR 45-59 (HR 0.60; 95% CI 0.39-0.93) saw lower mortality with earlier treatment. Survival was similar irrespective of angiography timing for patients with eGFR 30-44 (HR 0.75; 95% CI 0.48-1.18) and eGFR < 30 (HR 1.33; 95% CI 0.83-2.11).

Beyond treatment strategy and CKD, additional predictors of worse survival among the NSTEMI patients were age, male sex, heart failure, diabetes, peripheral artery disease, smoking and chronic obstructive pulmonary disease, higher troponin, and lower hemoglobin levels.

Exactly why there was no difference by strategy in the moderate/severe CKD group isn’t certain, Maor observed. It may be that kidney-related factors are driving the mortality just as much as the heart. Moreover, patients with CKD are at high risk of procedural complications, such as contrast-induced nephropathy.

We have to individualize care—in appropriate patients, in the appropriate settings, and with the appropriate expertise, we should be able to do these procedures safely. Sripal Bangalore

The editorial notes that when early angiography is pursued, several protocols can be used to prevent side effects that might worsen outcomes among CKD patients. For contrast-associated acute kidney injury (AKI), these include adequate hydration, a high statin dose, and limiting the volume of contrast media. For AKI not linked to contrast, options are maintaining hemodynamic conditions and systemic acid-base balance as well as limiting nephrotoxic drugs. Finally, antithrombotic treatment should be informed by ischemic and bleeding risk.

Briguori and Roscigno do inject a note of caution about the current data. “The present study should be interpreted within the boundary of its limitations, including the retrospective design and the ‘physician decision’ for an early or a delayed strategy,” they advise, adding that no adjustment can fully erase the impact of selection bias.

For Bangalore, an RCT is still within the realm of possibility. The practice patterns seen here hint that “there is likely enough equipoise to do a randomized trial,” he observed. What jumps out to him, said Bangalore, is how poorly the patients with the most-severe CKD fared: 51% of the early-angiography group and 58% of the delayed group with eGFR < 30 died over 4-year follow-up. “Something urgently needs to be done to reduce their overall risk, I think, that goes beyond revascularization.”

Moving ahead, a key question is how to risk stratify among the NSTEMI patients with moderate/severe CKD, Maor said. The current study wasn’t large enough for these subanalyses. “Future studies will have to address this [very important] question,” he concluded.

Sources
  • Sharon A, Massalha E, Fishman B, et al. Early invasive strategy and outcome of non–ST-segment elevation myocardial infarction patients with chronic kidney disease. J Am Coll Cardiol Intv. 2022;15:1977-1988.

  • Briguori C, Roscigno G. NSTEMI in chronic kidney disease patients: when following the heart is not always recommended. J Am Coll Cardiol Intv. 2022;15:1989-1991.

Disclosures
  • Sharon, Maor, Briguori, and Roscigno report no relevant conflicts of interest.
  • Bangalore reports having consultant/advisory board relationships with Abbott Vascular, Biotronik, Pfizer, Amgen, and Reata; receiving honoraria from Abbott Vascular, Biotronik, Pfizer, and Amgen; and receiving research grants from Abbott Vascular and the National Heart, Lung, and Blood Institute.

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