Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD: A Randomized Noninferiority Trial

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Figure 1.
Patient disposition. The most common reason for discontinuation in patients in the ‘other’ category was the patient moving away from participating dialysis units. *Kidney transplant was a prespecified reason for withdrawal from the trial.
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Figure 2.
Hematologic and iron parameters during the study. (A) Hemoglobin, (B) ferritin, and (C) transferrin saturation. Values shown are median with IQRs.
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Figure 3.
Time-to-event curves. (A) Death from any cause, nonfatal stroke, or nonfatal myocardial infarction (primary end point) and (B) death from any cause.
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Figure 4.
Subgroup analysis of the primary end point by baseline patient and disease factors.

Table 1.

Baseline characteristics of the patients

Characteristic, n (%)	Reference ESA (n=1409)	Methoxy Polyethylene Glycol-Epoetin Beta (n=1409)
Median age, yr (interquartile range)	65 (53–74)	64 (53–74)
Men	828 (59)	805 (57)
Region
Europe	1038 (74)	1039 (74)
Asia	162 (11)	150 (11)
Australia	73 (5)	75 (5)
Latin America	136 (10)	145 (10)
Treatment condition
Correction	273 (19)	273 (19)
Maintenance	1136 (81)	1136 (81)
On dialysis	1173 (83)	1194 (85)
Years receiving dialysis	n=1173	n=1194
<1	290 (25)	288 (24)
1–3	432 (37)	429 (36)
>3	451 (38)	477 (40)
Dialysis modality	n=1173	n=1194
Peritoneal dialysis	81 (7)	91 (8)
Hemodialysis	1092 (93)	1103 (92)
Cardiovascular risk factors and history
Ischemic heart disease	420 (30)	376 (27)
Peripheral vascular disease	234 (17)	200 (14)
Cerebral vascular disease	137 (10)	131 (9)
Congestive heart failure	202 (14)	192 (14)
NYHA class I	54 (4)	47 (3)
NYHA class II	121 (9)	112 (8)
NYHA class III	30 (2)	41 (3)
NYHA class IV	10 (1)	15 (1)
Unknown	5 (0)	0 (0)
Venous thrombosis	165 (12)	164 (12)
Hypertension	1267 (90)	1268 (90)
Hyperlipidemia	776 (55)	759 (54)
Diabetes	495 (35)	496 (35)
C-reactive protein ≤30 mg/L	1288/1386 (93)	1283/1379 (93)

There were no significant differences between the two arms with regard to any baseline characteristics. ESA, erythropoiesis-stimulating agent; NYHA, New York Heart Association.

Table 2.

Major safety end points

End Point	Reference ESA (n=1409)	Methoxy Polyethylene Glycol-Epoetin Beta (n=1409)	Hazard Ratio (95% CI)	P Value
End Point	No. of Patients (%)	No. of Patients (%)	Hazard Ratio (95% CI)	For Noninferiority^a	For Difference^b
Primary end point (composite of all-cause death, nonfatal MI, and nonfatal stroke)	644 (46)	640 (45)	1.03 (0.93 to 1.15)	0.004	0.54
Secondary end point
Death	557 (40)	558 (40)	1.06 (0.94 to 1.19)		0.36
Nonfatal MI or stroke	191 (14)	168 (12)	0.91 (0.74 to 1.12)		0.39
Fatal or nonfatal MI	158 (11)	143 (10)	0.95 (0.76 to 1.19)		0.66
Fatal or nonfatal stroke	98 (7)	89 (6)	0.94 (0.70 to 1.25)		0.66

ESA, erythropoiesis-stimulating agent; 95% CI, 95% confidence interval; MI, myocardial infarction.
↵a P value for the test for noninferiority at a hazard ratio of 1.20 (primary endpoint only).
↵b P value from the Wald test for hazard ratio difference from 1.