HORIZONS-AMI: CKD Patients Fare Poorly Regardless of Stent Type, Antithrombotic Regimen
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In patients with ST-segment elevation myocardial infarction (STEMI), chronic kidney disease (CKD) augments the risk of adverse events at 3 years after percutaneous coronary intervention (PCI), according to new subanalysis of the HORIZONS-AMI trial published in the September 2011 issue of JACC: Cardiovascular Interventions.
Moreover, such patients saw equally poor events regardless of whether they received bivalirudin vs. heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), or were implanted with DES vs. BMS.
The randomized, multicenter HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial compared bivalirudin with heparin plus a GPI in 3,602 STEMI patients. Of these patients, 3,000 were eligible for randomization in a 3:1 ratio to either paclitaxel-eluting Taxus stents (n = 2,257) or Express BMS (n = 749). Both devices are manufactured by Boston Scientific (Natick, MA).
CKD Predicts Worse Outcomes
In the current subanalysis, Roxana Mehran, MD, of Mount Sinai School of Medicine (New York, NY), and colleagues examined the 3-year outcomes of 554 of the 3,397 patients with available baseline creatinine levels (16.3%) who were classified as having CKD (defined as creatinine clearance < 60 mL/min). Endpoints included MACE (death, reinfarction, ischemic TVR, or stroke) and non-CABG-related major bleeding as well as net adverse clinical events (NACE; non-CABG-related major bleeding plus MACE).
Compared with patients who did not have CKD, those with impaired renal function showed higher NACE rates at 30 days (21.3% vs. 9.0%; P < 0.0001). The same pattern held true out to 3 years for NACE and all its components except ischemic TVR (table 1).
Table 1. Clinical Event Rates at 3 Years
|
CKD |
No CKD |
P Value |
NACE |
41.4% |
23.8% |
< 0.0001 |
MACE |
16% |
11.1% |
0.003 |
Major Bleeding |
19.3% |
6.7% |
< 0.0001 |
Stroke |
3.2% |
1.6% |
0.001 |
Death |
18.7% |
4.4% |
< 0.0001 |
Multivariate analysis confirmed that baseline creatinine was an independent predictor of NACE, MACE, death, and non-CABG major bleeding (table 2).
Table 2. Risk of Outcomes at 3 Years: CKD vs. No CKD
|
HR (95% CI) |
P Value |
NACE |
1.39 (1.24-1.56) |
< 0.0001 |
MACE |
1.38 (1.20-1.59) |
< 0.0001 |
Death |
1.51 (1.21-1.87) |
< 0.001 |
Major Bleeding |
1.43 (1.26-1.62) |
< 0.0001 |
Notably, the overall results of HORIZONS-AMI did not extend to the CKD subgroup.
In the HORIZONS stent arm as a whole, patients who received DES experienced a 40% reduction in ischemic TLR at 3 years compared with those given BMS. But TVR rates were equivalent among CKD patients regardless of whether they received DES or BMS (14.1% vs. 15.1%; P = 0.8).
And in the trial’s drug arm, bivalirudin significantly reduced the likelihood of non-CABG major bleeding by 36%, reinfarction by 24%, cardiac mortality by 44% and all-cause mortality by 25% compared with heparin plus a GPI at 3-year follow-up. CKD patients, however, had similar event rates irrespective of their assigned antithrombotic regimen.
Lack of Benefit in CKD Patients Unexpected
The fact that CKD worsens outcomes for STEMI patients is “[c]onsistent with previous reports,” Dr. Mehran and colleagues say, because such patients have more cardiac risk factors and comorbid conditions. Bleeding is a particular issue to be wary of when treating CKD patients, one that “may be attributed to functional abnormalities in platelets and coagulation factors,” they note.But the current results contradict earlier findings on antithrombotic use—including subgroup analyses from ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) and REPLACE-2 (Second Randomized Evaluation in PCI Linking Bivalirudin to Reduced Clinical Events)—which found bivalirudin to reduce bleeding compared with heparin plus a GPI in CKD patients. “Somewhat surprisingly, [the advantages of bivalirudin] were restricted largely to patients without CKD,” in HORIZONS-AMI, the investigators write.
Dr. Mehran and colleagues point out that although HORIZONS-AMI was designed to include the CKD subgroup analysis, it was not powered to provide conclusive evidence of superiority or noninferiority in these patients. In fact, with 7.4% of HORIZONS subjects lacking baseline creatinine measurements, the researchers “cannot exclude the possibility that chance may explain the differences between the present and prior bivalirudin trials in patients with CKD.”
Note: Dr. Mehran and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Source:
Saltzman AJ, Stone GW, Claessen BE, et al. Long-term impact of chronic kidney disease in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: The HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol Intv. 2011;4:1011-1019.
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Disclosures
- Dr. Mehran reports serving on the advisory board of Abbott Vascular, Ortho McNeil, and Regado Biosciences and receiving research support from BMS/Sanofi-Aventis.
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