Utilizing enoxaparin in the management of STEMI

Figures & data

Table 1 Design of the Studies

	No of patients	General treatment	Active treatment	Control	Treatment duration
Enoxaparin versus placebo
Glick et al (1996)	103	SK + ASA + UFH iv	E 40 mg/die sc	placebo	25 days
Simoons et al (2002) (AMI-SK)	496	SK + ASA	E 30 mg iv + E 1 mg/kg sc × 2	placebo	3–8 days
Enoxaparin versus UFH
Ross et al (2001) (HART-II)	400	rt-PA + ASA	E 30 mg iv + E 1mg/kg sc × 2	UFH 5.000 IU iv + 15 IU/kg/h iv	3 days
ASSENT-3 (2001)	6095	–	– full-dose TNK + ASA + E 30mg iv + 1 mg/kg sc × 2	–	7 days E/48 h UFH
			– full-dose TNK + ASA + UFH 60 IU/kg iv +12 IU/kg/h iv	–
			– half-dose TNK + ASA + UFH 40 IU/kg +7 IU/kg iv + abciximab 12 h	–
Antman et al (2002) (ENTIRE-TIMI 23)	483	–	as in ASSENT–3 trial + – half-dose TNK + ASA + E 1 mg/kg sc × 2 + abciximab 12 h		≤8 days E/≤ 36 h UFH
Baird et al (2002)	300	Thrombolytic	E 40 mg iv + 40 mg sc × 3	UFH 5.000 IU iv + 30.000 IU iv 24 h	4 days
Wallentin et al (2003) (ASSENT-3 PLUS)	1639	TNK + ASA	E 30 mg iv + E 1 mg/kg sc × 2	UFH 60 IU/kg + 12 IU/kg/h iv	≤7 days E/48 h UFH
Tatu-Chitoiu et al (2004) (ASENOX)	429	ASK + ASA + E 40 mg iv +	E 40 mg iv + E 1 mg/kg sc × 2	UFH 1.000 IU/h iv	≤7 days E/≤ 72 h UFH

Abbreviations: E, enoxaparin; rt-PA, alteplase; SK, streptokinase; ASK, accelerate regimen of streptokinase in 20 min; TNK, tenecteplase; ASA, aspirin; UFH, unfractionated heparin; IRA, infarct-related artery; sc, subcutaneously; iv, intravenously; h, hours

Table 2 Results of the studies

	End points	Active treatment	Control	p
Enoxaparin versus placebo
Glick et al (1996)	1○: death, reinfarction, angina at 6 months	14%	43%	<0.05
Simoons et al (2002) (AMI-SK)	1○: TIMI 3 grade flow at 5–10 days	70%	58%	<0.05
	2○: death, reinfarction, angina at 30 days	13%	21%	<0.05
	2○: major bleeding at 30 days	5%	3%	NS
Enoxaparin versus UFH
Ross et al (2001) (HART-II)	1○: TIMI 2–3 grade flow in IRA at 90’	80%	75%	NS
	2○: in-hospital major bleedings	5.6%	5%	NS
ASSENT-3 (2001)	1○: death at 30 days, in-hospital reinfarction/angina	11%	15%	<0.05
	1○: previous + in-hospital major bleedings	14%	17%	<0.05
	2○: in-hospital reinfarction/refractory ischemia	3/5 %	4/7%	<0.05
	2○: in-hospital major bleendigs	3%	2%	NS
Antman et al (2002) (ENTIRE-TIMI 23)	1○: TIMI grade 3 flow at 60’	50%	51%	NS
	1○: major bleedings at 30 days	2%	2%	NS
	2○: death, reinfarction at 30 days	4%	16%	<0.05
Baird et al (2002)	1○: death, reinfarction, angina at 90 days	26%	36%	<0.05
	2○: major bleeding at 4 days	3%	4%	NS
Wallentin et al (2003) (ASSENT-3 PLUS)	1○: death at 30 days, in-hospital reinfarction/angina	14%	17%	NS
	1○: previous + in-hospital major bleedings	18%	20%	NS
	2○: stroke + intracranial hemorrhage	2%	1%	NS
Tatu-Chitoiu et al (2004) (ASENOX)	1○: Reperfusion rate (noninvasive criteria)	78%	74%	NS
	2○: mortality at 30 days	6%	7%	NS

Abbreviations: 1○, primary end-point; 2○, secondary end-point; IRA, infarct-related artery.

Table 3 Pooled analysis of the results and relative risk (RR) of in-hospital/7-day reinfarction and death in the open-label studies

	In-hospital/7-day death + reinfarction		Risk ratio (95% confidence intervals)	In-hospital/7-day reinfarction		Risk ratio (95% confidence intervals)	In-hospital/7-day death		Risk ratio (95% confidence intervals)
	Enoxaparin	UFH		Enoxaparin	UFH		Enoxaparin	UFH
Ross et al (2001) (HART-II)	–	–	–	–	–	–	8/196	9/197	0.89 (0.34–2.35)
ASSENT-3 (2001)	–	–	–	54/2040	86/2038	0.62 (0.44–0.87)	–	–	–
Antman et al (2002) (ENTIRE-TIMI 23)	–	–	–	–	–	–	–	–	–
Wallentin et al (2003) (ASSENT-3 PLUS)	–	–	–	29/818	48/821	0.59 (0.37–0.95)	–	–	–
Total	–	–	–	83/2858	134/2859	0.61 (0.46–0.80)	8/196	9/197	0.89 (0.34–2.35)

Table 4 Pooled analysis of the results and Relative Risk (RR) of 30-day reinfarction and death in the open-label studies

	30-day death + reinfarction		Risk ratio (95% confidence intervals)	30-day reinfarction		Risk ratio (95% confidence intervals)	30-day death		Risk ratio (95% confidence intervals)
	Enoxaparin	UFH		Enoxaparin	UFH		Enoxaparin	UFH
Ross et al (2001) (HART-II)	–	–	–	–	–	–	–	–	–
ASSENT-3 (2001)	233/2037	314/2038	0.71 (0.59–0.85)	–	–	–	109/2037	122/2038	0.89 (0.68–1.16)
Antman et al (2002) (ENTIRE-TIMi 23)	16/324	17/159	0.43 (0.21–0.88)	–	–	–	–	–	–
Wallentin et al (2003) (ASSENT-3 PLUS)	116/817	142/818	0.79 (0.60–1.03)	–	–	–	61/817	49/818	1.27 (0.86–1.87)
Tatu-Chitoiu et al (2004) (ASENOX)	–	–	–	–	–	–	10/165	18/264	0.88 (0.40–1.96)
Total	365/3178	473/3015	0.70 (0.60–0.81)				180/3019	189/3120	0.98 (0.80–1.21)

Table 5 Pooled analysis of the results and relative risk (RR) of in-hospital/7 days and 30-day major bleedings in the open-label studies

	In-hospital/7-day major bleedings*		Risk ratio (95% confidence intervals)	30-day major bleedings*		Risk ratio (95% confidence intervals)
	Enoxaparin	UFH		Enoxaparin	UFH
Ross et al (2001) (HART-II)	7/196	6/197	1.18 (0.39–3.57)	–	–	–
ASSENT-3 (2001)	80/2040	106/2038	1.38 (1.02–1.86)	–	–	–
Antman et al (2002) (ENTIRE-TIMI 23)	–	–	–	16/324	6/159	1.33 (0.51–3.45)
Wallentin et al (2003) (ASSENT-3 PLUS)	33/817	23/821	1.46 (0.85–2.51)	–	–	–
Tatu-Chitoiu et al (2004) (ASENOX)	–	–	–	0/165	2/264	(not applicable)
Total	120/3053	135/3056	0.86 (0.69–1.14)	16/489	8/423	1.76 (0.74–4.14)

* evaluated in the treated population.

Figure 1 Efficacy and safety outcomes at 8 days in the ExTRACT-TIMI 25 study.

Abbreviations: UFH, unfractionated heparin; ICH, intracranial hemorrhage; RR, relative risk; NS, nonsignificant.

Figure 2 Efficacy and safety outcomes at 30 days in the ExTRACT-TIMI 25 study.

Abbreviations: UFH, unfractionated heparin; ICH, intracranial hemorrhage; RR, relative risk; NS, nonsignificant.

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