BLEED-Myocardial Infarction Score: Predicting mid-term post-discharge bleeding events

Table 1 Prediction of mid-term bleeding events in univariate analysis

	Bleeding event	No bleeding event	P value
Age (yr)	74.6	67.2	< 0.001
Female gender	41.40%	34.50%	0.292
NSTEMI	67.20%	57.50%	0.095
Diabetes mellitus	50.00%	33.50%	0.011
Previous arterial hypertension	84.50%	73.80%	0.072
Smoking habits	29.30%	17.20%	0.049
History of stroke/TIA	17.50%	8.10%	0.015
Atrial fibrillation at admission	16.70%	13.50%	0.516
Bleeding during hospitalization	19.30%	7.10%	0.001
Maximum killip class	1.62	1.39	0.004
Hemoglobin at admission (g/dL)	12.0	13.5	< 0.001
GFR at admission (mL/min)	55.0	71.6	< 0.001
Blood urea nitrogen at admission (mg/dL)	13.5	8.7	< 0.001
Submitted to revascularization procedures	58.60%	63.90%	0.422

NSTEMI: Non-ST elevation myocardial infarction; TIA: Transient ischaemic attack; GFR: Glomerular filtration rate.

Table 2 Calculation of the BLEED-myocardial infarction score

Variable	Points assigned
Age (yr)
< 65	0
65-74	1
≥ 75	2
GFR at admission (MDRD formula, mL/min)
≥ 60	0
30-59.9	1
< 30	2
History of stroke or transient ischemic attack1
No	0
Yes	1
Heart failure during hospitalization2
No	0
Yes	1
History of hypertension
No	0
Yes	1
Antithrombotic therapy3
1 agent	1
2 agents	2
3 agents	3
Hemoglobin at admission (g/dL)
≥ 12	0
10-11.9	1
< 10	2
Blood urea nitrogen at admission (mg/dL)
< 10	0
10-25	1
> 25	2
History of major hemorrhage or bleeding event during hospitalization4
No	0
Yes	1
Smoking habits (until hospitalization)
No	0
Yes	1
History of diabetes mellitus
No	0
Yes	1

The BLEED-myocardial infarction (MI) score is obtained by summing all the points assigned for each predictor.

¹Previous neurologic events were defined as history of sudden onset of a focal neurologic deficit in a location consistent with the territory of a major cerebral artery or the radiological documentation of previous cerebral infarction (irrespective of the presence/absence of symptoms);

²Heart failure was defined as a maximum Killip Class > 1 at any time during hospitalization. Therefore, it includes both patients with previous history of heart failure and those with de novo heart failure during hospitalization;

³Including anti-platelet agents (such as Acetylsalicylic Acid and Clopidogrel) and/or anticoagulants (such as Warfarin). At the time patients assigned to the derivation sample were admitted to our Acute Cardiac Care Unit, agents such as Prasugrel, Ticagrelor or Dabigatran were not available;

⁴History of major hemorrhage defined as previous non-fatal hemorrhagic stroke or history of serious bleeding requiring transfusion. Bleeding event during hospitalization represents the occurrence of a hemorrhagic episode during hospitalization for the MI index, as described for the primary endpoint, plus any significant bleeding event attributable to revascularization procedures (again, as described for the primary endpoint). GFR: Glomerular filtration rate.

Table 3 Description of derivation and validation samples

Characteristic	Derivation sample (n = 1050)	Validation sample (n = 852)
Age (yr)	67.9 ± 13.5	67.9 ± 13.6
Male gender	686 (64.7)	578 (68.0)
Type of myocardial infarction
STEMI	42.1%	38.8%
NSTEMI	57.9%	61.2%
Diabetes mellitus	380 (35.9)	266 (31.2)
Previous hypertension	796 (75.2)	631 (74.2)
Hyperlipidemia	59629 (56.3)	475 (59.6)
Smoking habits	287 (27.1)	281 (33.1)
Previously known coronary disease	283 (26.7)	243 (28.6)
History of stroke/TIA	94 (9.0)	77 (9.1)
Atrial fibrillation at admission	144 (13.7)	99 (12.4)
Admission killip class	1.40 ± 0.6	1.36 ± 0.7
Maximum killip class	1.56 ± 0.8	1.46 ± 0.8
Average number of vessels with significant lesions	1.60 ± 0.97	1.54 ± 0.99
GFR at admission	68.6 ± 38.4	72.6 ± 32.0
BUN at admission (mmol/L)	9.58 ± 6.81	8.85 ± 6.20
Hemoglobin at admission (mg/dL)	13.3 ± 2.1	13.8 ± 6.14
NT-proBNP at admission (ng/L)	4202 ± 13400	6393 ± 15950
Submitted to revascularization procedures	645 (61.4)	663 (77.8)
Clinically significant bleeding during hospitalization	87 (8.3)	55 (6.5)
Average GRACE score for intrahospital mortality	153.9 (P25 124; P50 151; P75 179)	145.6 (P25 114; P50 143; P75 173)
Average GRACE score for 6-mo mortality	128.0 (P25 102; P50 125; P75 149)	121.0 (P25 94; P50 118; P75 145)
Moderate-severe left ventricular systolic dysfunction	19.50%	23.00%
Discharged on dual anti-platelet therapy	818 (89.2)	723 (90.6)
Discharged on anticoagulant treatment	36 (3.9)	37 (4.6)
Intrahospital mortality	8.60%	6.10%
Post-discharge mortality (mo)	165 (16.5) (Follow-up: 19.9 ± 6.7)	88 (11.0) (Follow-up: 13.4 ± 8.1)
Bleeding events during follow-up (mo)	62 (6.8) (Follow-up: 19.9 ± 6.7)	60 (7.5) (Follow-up: 13.4 ± 8.1)

Data are expressed as absolute numbers (percentage) or mean ± SD. TIA: Transient ischaemic attack; BUN: Blood urea nitrogen; CRP: C-reactive protein; NSTEMI: Non-ST elevation myocardial infarction; STEMI: ST elevation myocardial infarction.

Table 4 Hemorrhagic and combined event rates according to the BLEED-myocardial infarction score risk-group stratification

	Category	Low risk	Intermediate risk	High risk	Gamma for trend	P value
Clinically significant bleeding events
Derivation cohort (follow-up: 19.9 ± 6.7 mo)	Incidence	0.80%	3.40%	14.40%	0.70 ± 0.08	< 0.001
Validation cohort (follow-up: 13.4 ± 8.1 mo)	Incidence	1.30%	5.00%	14.10%	0.61 ± 0.08	< 0.001
Composite endpoint (bleeding + all-cause mortality)
Derivation cohort (follow-up: 19.9 ± 6.7 mo)	Incidence	3.10%	11.40%	45.70%	0.76 ± 0.04	< 0.001
Validation cohort (follow-up: 13.4 ± 8.1 mo)	Incidence	1.30%	9.30%	31.30%	0.73 ± 0.05	< 0.001

Table 5 Primary and secondary endpoint event rates according to the BLEED-myocardial infarction score

Sample	BLEED-MI score	Bleeding event rate	Composite endpoint event rate
Derivation sample	0-1	0.80%	3.10%
	2-3	2.70%	10.00%
	4-5	7.90%	19.10%
	6-7	13.60%	50.40%
	8-9	20.00%	65.90%
	10-11	25.00%	71.40%
Gamma for trend		0.60 ± 0.07	0.70 ± 0.04
P value		< 0.001	< 0.001
Validation sample	0-1	0.00%	0.00%
	2-3	1.20%	1.80%
	4-5	5.40%	8.80%
	6-7	6.50%	16.10%
	8-9	13.90%	25.70%
	10-11	17.80%	39.70%
	12-13	23.10%	48.00%
	14-15	-	60.00%
Gamma for trend		0.52 ± 0.07	0.63 ± 0.05
P value		< 0.001	< 0.001

MI: Myocardial infarction.

Table 6 Number of patients reaching the primary endpoint in the validation sample at different time points

Time (mo)	Low risk	Intermediate risk	High risk
0-3	1	4	21
4-6	0	5	3
7-9	1	4	6
10-12	0	3	4
13-15	0	0	3
16-18	0	0	0
19-21	0	0	1
22-24	0	0	1