J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Review

Volume 5, Number 4, August 2013, pages 251-265

The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future

**Table 1.** Comparison of the Properties of Streptokinase, Alteplase and Reteplase
	Streptokinase	Alteplase	Reteplase	Desmoteplase
Molecular weight	47k daltons	70k daltons	39k daltons	52k daltons
Half-life	23 mins	Less than 5 mins	13 - 15 mins	4 hours
Plasminogen activation	Indirect binding	Direct binding	Direct binding	Direct binding
Fibrin selective	No	Yes	Yes	Fibrin specific
Allergic response	Yes	No	No	Yes
Administration	Infusion	Infusion	bolus	Bolus

Table 1. Comparison of the Properties of Streptokinase, Alteplase and Reteplase

Streptokinase

Alteplase

Reteplase

Desmoteplase

Molecular weight

47k daltons

70k daltons

39k daltons

52k daltons

Half-life

23 mins

Less than 5 mins

13 - 15 mins

4 hours

Plasminogen activation

Indirect binding

Direct binding

Fibrin selective

Yes

Fibrin specific

Allergic response

Yes

Administration

Infusion

bolus

Bolus

**Table 2.** Arterial Occlusions and Recanalization Patterns in Some Clinical Trials in Acute Ischemic Stroke
TRIAL	Treatment	Number of patients	Highest reported recanalization rate (%)	Assessment of recanalization
NINDS [9] Active	IV-tPA	312	--
Control	Placebo	312	--	None
ECASS-3 [10] Active	IV-tPA	418	--	None
(3 - 4.5 hours) Control	Placebo	403	--
DIAS (3 - 9 hours) [18] Active	IV-Desmotepase	71 (Total)	49
Part-1 25 mg		16	56
37.5/50 mg		13	46
Part-2 62.5 µg/kg		13	23	MRA-complete or partial recanalization
90 µg/kg		15	47
125 µg/kg		14	71
Control		26	19
Part-1	Placebo	16	19
Part-2		10	20
DIAS-II (3 - 9 hours) [20] Active	IV-Desmoteplase
90 µg/kg		57
125 µg/kg		66
Control	Placebo	63
Active PROACT-II [35]	IA r-proUK	121	66	Cerebral Angiography (TIMI 2 + 3)
(TIMI 2 + 3) Control	Placebo	59	18
Active	IV + IA TPA	11	81
				Cerebral Angiography
IMS [69] Control	Placebo + IA TPA	10	50
Active	MERCI ± Lytic
MCA		80	45	Cerebral Angiography (any recanalization)
ICA		47	53
MERCI [44] VA/BA		14	50
Control	--	59	18
	Placebo cases from PROACT-2
Active	IV-tPA + TCD	63	38
CLOTBUST [28] (at 2 hours) Control	IV-tPA	63	13	TCD
Active	IV-tPA + Ultrasound	14	29.3
TRUMBI [29] Control	IV-TPA	12	50.0	MRA

Table 2. Arterial Occlusions and Recanalization Patterns in Some Clinical Trials in Acute Ischemic Stroke

TRIAL

Treatment

Number of patients

Highest reported recanalization rate (%)

Assessment of recanalization

NINDS [9] Active

IV-tPA

312

Control

Placebo

312

None

ECASS-3 [10] Active

IV-tPA

418

None

(3 - 4.5 hours) Control

Placebo

403

DIAS (3 - 9 hours) [18] Active

IV-Desmotepase

71 (Total)

Part-1 25 mg

37.5/50 mg

Part-2 62.5 µg/kg

MRA-complete or
partial recanalization

90 µg/kg

125 µg/kg

Control

Part-1

Placebo

Part-2

DIAS-II (3 - 9 hours) [20] Active

IV-Desmoteplase

90 µg/kg

125 µg/kg

Control

Placebo

Active PROACT-II [35]

IA r-proUK

121

Cerebral
Angiography
(TIMI 2 + 3)

(TIMI 2 + 3) Control

Placebo

Active

IV + IA TPA

Cerebral
Angiography

IMS [69] Control

Placebo + IA TPA

Active

MERCI ± Lytic

MCA

Cerebral
Angiography
(any recanalization)

ICA

MERCI [44] VA/BA

Control

Placebo cases from PROACT-2

Active

IV-tPA + TCD

CLOTBUST [28] (at 2 hours) Control

IV-tPA

TCD

Active

IV-tPA + Ultrasound

29.3

TRUMBI [29] Control

IV-TPA

50.0

MRA

**Table 3.** Comparative Rates of Recanalization, Symptomatic Intracranial Hemorrhage and Functional Outcome in Various Clinical Trials
Revascularization approach	Partial and incomplete recanalization (%)	SICH	mRS 0 - 2 at 3 months
tPA: tissue plasminogen activator; SICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; PRO-UK: Pro-Urokinase.
IV tPA < 3 hrs CLOTBUST [28], TUCSON [80]	40	4.4	39
IA Pro-urokinase < 6 hrs PROACT II trial [35]	66	10	40
IV tPA < 3 hrs + IA tPA IMS II trial [70]	64	9.9	38
Merci^TM < 8 hrs [44], Multi-Merci Study [50]	57	9.8	36
Penumbra^TM < 8 hrs Penumbra clinical study [55]	82	11.2	25
IV tPA sonothrombolysis < 3hrs CLOTBUST tPA + TCD arm [28]	83	3.8	51

Table 3. Comparative Rates of Recanalization, Symptomatic Intracranial Hemorrhage and Functional Outcome in Various Clinical Trials

Revascularization approach

Partial and incomplete recanalization (%)

SICH

mRS 0 - 2 at 3 months

tPA: tissue plasminogen activator; SICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; PRO-UK: Pro-Urokinase.

IV tPA < 3 hrs CLOTBUST [28], TUCSON [80]

4.4

IA Pro-urokinase < 6 hrs PROACT II trial [35]

IV tPA < 3 hrs + IA tPA IMS II trial [70]

9.9

Merci^TM < 8 hrs [44], Multi-Merci Study [50]

9.8

Penumbra^TM < 8 hrs Penumbra clinical study [55]

11.2

IV tPA sonothrombolysis < 3hrs CLOTBUST tPA + TCD arm [28]

3.8