Update on the clinical use of the low-molecular-weight heparin, parnaparin

Figures & data

Table 1 Clinical experience with parnaparin for prophylaxis of venous thromboembolism

Author	Year	Setting	Design	End-point assessment	Patientsa	Parnaparin (IUaXa) sc	Comparator	Treatment duration	Follow-up	Deep-vein thrombosisb	Pulmonary embolismb	Bleeding^†
Verardi et al^Citation32	1988	Major general surgery	PG	RFUT, CWD, SGP, V	610 (308/302)	3200 or 6400 od	UFH 5000 IU bid or tid sc	7 days	none	3.2/6.3 (<0.05)	0.32/1.0 (>0.05)	0.97/3.6 (0.032)
Gossetti et al^Citation40	1988	Vascular surgery	C	RFUT, CWD, US	40	6400 od	–	9 days	none	2.5	NR	NR
Gruttadauria et al^Citation36	1988	General surgery	PG	RFUT, CWD	179 (89/90)	3200 od	UFH 5000 IU bid	7 days	none	2.2/4.4 (0.68)	NR	3.4/12.2 (0.048)
Bonomo et al^Citation39	1988	General surgery	C	IPG, V	78	3200 od	–	7 days	none	2.3	NR	2.3
Chiapuzzo et al^Citation16	1988	Major orthopedic surgery	PG	RFUT, CWD	140 (70/70)	3200 od	UFH 5000 IU tid sc	7 days	none	7.1/10.0 (0.66)	0/0	4.2/7.1 (0.6)
Catania et al^Citation35	1988	General surgery	R, O	CWD, CXr	173 (88/85)	3200 od	UFH 5000 IU tid sc	7 days	none	1.1/7.1 (0.038)	0/1.2 (0.25)	0/0
Mascali et al^Citation33	1988	Major orthopedic surgery	PG	DUS	136 (68/68)	3200 bid	UFH 5000 IU tid sc	7 days	none	1.5/2.4 (1.00)	NR	2.9/13.4 (0.55)
Speziale et al^Citation14	1988	Vascular surgery	R, O	RFUT	92 (46/46)	6400 od	UFH 5000 IU bid	7 days	none	6.5/8.6 (0.86)	NR	8.7/17.4 (0.29)
Valle et al^Citation28	1988	General surgery	R, DB	CWD	100 (50/50)	3200 od	Placebo	7 days	none	0.0/6.0 (0.24)	NR	2.0/6.0 (0.61)
Pellegrino et al^Citation42	1988	Urologic surgery	C	CE, V	87	3200 or 6400 od	–	7 days	none	2.3	0	2.3
Cortellini et al^Citation43	1988	Urologic surgery	C	IPG	80	3200 or 6400 od	–	7 days	none	6.2	NR	5.0
Salcuni et al^Citation37	1988	Major general surgery	R, O	Phy, CWD, CXr	141 (73/68)	3200 od	UFH 5000 IU tid sc	7 days	none	4.1/10.3 (0.15)	1.4/2.9 (0.61)	8.2/7.3 (0.88)
Forzano et al^Citation29	1988	General surgery	R, DB	CWD	100 (50/50)	3200 od	Placebo	7 days	none	2.0/12.0 (0.11)	NR	NR
Pini et al^Citation30	1989	Hip fracture surgery	R, O	RFUT, SGP, V	49 (25/24)	3200 bid	UFH 5000 IU tid sc	14 days, or discharge	none	20.0/29.2 (0.5)	0.0/12.5 (0.11)	12.0/8.3 (1.0)
Tartaglia et al^Citation44	1989	Gynecological surgery	C	CE, CWD, CXr	92	3200 od or 6400 od	–	7 days	none	3.3	0.0	NR
Corrado et al^Citation38	1988	Urologic surgery	R, SB	RFUT, CWD, IPG	58 (29/29)	6400 od	UFH 5000 IU bid sc	7 days	none	0.0/0.0	0.0/0.0	0.0/0.0
Verardi et al^Citation34	1989	Major general surgery	R, O	RFUT, CWD	88 (44/44)	6400 od	UFH 5000 IU bid sc	7 days	none	2.3/6.8 (0.62)	NR	0.0/0.0
Garcea et al^Citation15	1992	Major general surgery	R, O	RFUT, US, V, CXr, LS	90 (45/45)	3200 od	UFH 5000 IU tid sc	7 days	none	0.0/2.2 (1.0)	0.0/0.0	0.0/11.1 (0.056)
Gossetti et al^Citation41	1992	Major vascular surgery	C	RFUT, US	65	3200 od	–	8 days	none	1.5	NR	1.5
Beghi et al^Citation31	1993	Cardiac surgery	R, O	CWD, ECD	39 (20/19)	3200 od	UFH 5000 IU tid sc	4 days	none	0.0/0.0	NR	NR
Montebugnoli et al^Citation45	2005	Minor orthopedic surgery	C	CUS	509	3200 or 4250 od	–	10 days	none	0.0	0.0	1.6
Forestieri et al^Citation22	2007	Bariatric surgery	C	ECD, LS	10	6400 odc	–	30 days	none	0.0	10.0	NR

a total number (parnaparin group/comparator group)

b frequency of outcome events in the parnaparin group/in the comparator group (p value)

c plus intermittent pneumatic compression (during hospitalization) and stockings (up to 30 days).

Abbreviations: PG, parallel-group, nonrandomized; C, cohort study; R, randomized; O, open; SB, single blind; DB, double blind; CE, clinical evaluation; RFUT, radio-labeled fibrinogen uptake test; SGP, strain-gauge plethysmography; IPG, impedance plethysmography; V, venography; CWD, continuous wave Doppler sonography; US, ultrasonography; DUS, Doppler ultrasonography; CUS, compression ultrasonography; ECD, echo-color Doppler ultrasonography; CXr, chest X-ray; LS, lung scan; sc, subcutaneously; od, once daily; bid: twice daily; tid: three times daily; NR. not reported.

Table 5 Clinical experience with parnaparin for the management of acute coronary syndromes

Author	Year	Target disease	Design	End-point definition	Patientsa	Parnaparin (IUaXa) sc	Comparator	Treatment duration	Follow-up	Efficacyb	Major bleedingb
Melandri et al^Citation62	1993	SA	R, DB	Time to ST segment depression, peak ST segment depression, time to onset of moderate angina (all after treadmill testing), Canadian Cardiovascular Society class for angina	29 (15/14)	6400 od	placebo	3 months		Only within-group analysis (time to ST segment depression, peak ST segment depression, and Canadian Cardiovascular Society class for angina were significantly improved in the parnaparin group)	NR
PRIME CARE investigators^Citation21	2005	UA	R, O	All-cause death, myocardial infarction, need for revascularization, major bleeding	897 (446/451)	6400 od	UFH bolus 5000 IU iv followed by 800–1000 IU/h for 48 h, then 5000 IU 4 × daily sc for 5 d	7 days	30 days	7.3/11.4 (RR 0.64; 95%CI 0.42–0.97, P = 0.034) 21.8/12.1 (RR 0.56; 95% CI 0.39–0.79, P = 0.0008)	0.4/0.4 (P = 1.0)
Wang et al^Citation23	2006	STEMI	R, O	All-cause death, recurrent myocardial infarction, need for emergency revascularization	186 (96/90)	4250 bid	UFH bolus 100 IU/kg iv followed by 1000 IU/h for 3 d, then 7500 IU bid sc for 4 d	7 days	45 days	27.1/42.2 (P = 0.03)c	2.1/4.4 (P = 0.43)

a total number (parnaparin group/comparator group);

b Frequency of outcome events in the parnaparin group/in the comparator group (P value);

c Assessed at 45 days.

Abbreviations: SA, stable angina; UA, unstable angina; STEMI, ST elevation myocardial infarction; R, randomized; O, open; DB, double blind; sc, subcutaneously; iv, intravenously; od, once daily; bid, twice daily; tid, three times daily; NR, not reported; h, hour; d, days.

Table 2 Clinical experience with parnaparin for the treatment of deep-vein thrombosis

Author	Year	Design	End-point assessment	Patientsa	Parnaparin (IUaXa) sc	Comparator	Treatment duration	Follow-up	Deep-vein thrombosisb	Pulmonary embolismb	Bleedingb
Notarbartolo et al^Citation46	1988	R, O	SGP	90 (30, 30/30)	6400 od or 12800 od 6400 od	UFH 30000 IU iv od warfarin	10 days 60 days	NR	0.0/0.0	NR	0/3.1 (0.034)
Zinicola et al^Citation50	1989	C	DS, LS	47	12800 od 6400 od	–	10 days 50 days	NR	0c	0	NR
Teoldi et al^Citation47	1993	R, SB	SGP, CE	40 (20/20)	6400 bid 6400 od	UFH 5000 IU sc tid UFH 5000 IU sc bid	15 days 30 days	NR	0.0/5.0 (1.0)	0.0/0.0	0.0/0.0
Bellosta et al^Citation49	2007	R, O	ECD	91 (51/40)	6400 bid for 1 month, then 6400 od	Nadroparin 11400 (<70 kg) or 15000 (>70 kg) sc od	3 or 6d months	NR	1.9/10.0 (0.16)^e	1.9/0.0 (1.0)	1.9/0.0 (1.0)
Vashist et al^Citation48	2006	R, O	ECD	100 (50/50)	6400 od plus VKI	UFH 10000 IU sc tid plus VKI	3 months	NR	0.0/0.0	0.0/2.0 (1.0)	0.0/0.0

a total number (parnaparin group/comparator group)

b frequency of outcome events in the parnaparin group/in the comparator group (P value)

c 1 superficial thrombophlebitis;

d in the case of unprovoked DVT

§ the figures reported refer to DVT extension, as assessed by ECD.

Abbreviations: R, randomized; O, open; C, cohort study; SB, single blind; CE, clinical evaluation; DS, doppler sonography; SGP, strain-gauge plethysmography; ECD, echo-color doppler ultrasonography; LS, lung scan; sc, subcutaneously; iv, intravenously; od, once daily; bid, twice daily; tid, three times daily; NR, not reported; VKI, vitamin K inhibitor.

Table 3 Clinical experience with parnaparin for the management of chronic venous disease

Author	Year	Target disease	Design	End-point definition	End-point Assessment	Patientsa	Parnaparin (IUaXa) sc	Comparator	Treatment duration	Follow-up	Efficacy	Safetyb
Verardi et al^Citation51	1988	PTS	R, O	Intensity of symptoms (scale 0–3), calf/ankle diameter	CE, DS (only if recurrent DVT)	77 (39/38)	30.000/day for 10 days, 15.000/day for up to 50 days	UFH 20.000 IU/day iv for 10 days UFH 12.500 IU sc for up to 50 days	10 to 50 days	None	c	7.0/8.0 (1.0)
Sannazzari et al^Citation52	1989	CVI	R, DB	Intensity of symptoms (scale 0–3), ankle diameter, venous outflow	CE, SGP	92 (30, 30/30)	3200 od or 6400 od	UFH 5.000 IU sc tid	30 days	None	Statistically significant improvement with Parnaparin 6400 IUaXa od compared to the other two groups	0.0, 0.0/6.7 (0.49)
Catania et al^Citation53	1993	PTS	R, SB	Intensity of symptoms (scale 0–3), venous outflow	CE, SGP, DS	46 (24/22)	4250 od	UFH 5.000 IU sc bid	90 days	None	c	None reported
Canova et al^Citation54	1993	PTS	R, SB	Intensity of symptoms (scale 0–3), venous outflow	CE, SGP, US	57 (27/30)	4250 od	UFH 5.000 IU sc tid	90 days	None	c	None reported
Della Marchina et al^Citation55	1993	CVI	R, SB	Intensity of symptoms (scale 0–3)	CE, SGP, US	70 (35/35)	4250 od	UFH 5.000 IU sc tid	90 days	None	c	8.6/17.1 (0.48)

a total number (parnaparin group/comparator group);

b frequency of outcome events in the parnaparin group/in the comparator group (P value);

c equivalent to comparator.

Abbreviations: PTS, post-thrombotic syndrome, CVI, chronic venous insufficiency; R. randomized; O, open; DB, double blind; SB, single blind; CE, clinical evaluation; DS, doppler sonography; SGP, strain-gauge plethysmography; US, ultrasonography; sc, subcutaneously; od, once daily; bid, twice daily; tid, three times daily; iv, intravenously.

Table 4 Clinical experience with parnaparin for the management of peripheral arterial occlusive disease

Author	Year	Target disease	Design	End-point definition	End-point Assessment	Patientsa	Parnaparin (IUaXa) sc	Comparator	Treatment duration	Follow-up	Efficacy	Safetyb
Di Stefano et al^Citation13	1988	PAOD	PG	Symptoms, PFWD, resting blood flow	CE (scale 0–3), TDM, DS	55 (27/28)	6400 od	UFH 5000 IU sc bid	7 months	None	Only within-group analysis (both improved)	Almost 100% of patients in both groups
Palmieri et al^Citation61	1988	PAOD Fontane 2	R, DB	ABI, pain-free walking time, peak blood flow	DS, SGP, TDM	55 (28/27)	6400 od	placebo	6 months	None	Only within-group analysis (ABI improved in both groups; pain free walking time, peak blood flow improved only by parnaparin)	4.0/2.0 (0.34)
Tesi et al^Citation59	1989	PAOD Fontaine 2	R, DB	ABI, PFWD	DS, TDM	20 (10/10)	6400 od	placebo	6 months	None	Parnaparin improved both ABI (P < 0.05) and PFWD (P = 0.03) as compared to placebo	None reported
Mannarino et al^Citation56	1991	PAOD Fontaine 2	R, DB	ABI, PFWD	DS, SGP, TDM	44 (22/22)	6400 od	placebo	6 months	None	Parnaparin improved PFWD (P < 0.05) as compared to placebo	None reported
Serrao et al^Citation60	1991	PAOD Fontaine 2–3	R, DB	Intensity of symptoms (scale 0–3), ABI, pain-free walking time	CE	40 (20/20)	6400 od	placebo	6 months	None	All outcomes significantly improved by Parnaparin as compared to placebo	5.0/1.7 (0.65)
Simoni et al^Citation58	1992	PAOD Fontaine 2	R, O	ABI, PFWD, resting and peak blood flow	DS, SGP, TDM	66 (33/33)	6400 od	placebo	6 months	None	Parnaparin significantly (P < 0.05) improved PFWD (+28.9%), ABI and peak flow compared to placebo	2.8/0.7 (0.49)
Calabrò et al^Citation57	1993	PAOD Fontaine 2	R, DB	ABI, PFWD, total walking distance, resting and peak blood flow	SGP, TD	36 (18/18)	6400 od	placebo	6 months	None	Only within-group analysis (PFWD and resting blood flow improved in the parnaparin group only)	None reported

a total number (parnaparin group/comparator group),

b Frequency of outcome events in the parnaparin group/in the comparator group (P value).

Abbreviations: PAOD, peripheral arterial occlusive disease, ABI, ankle-brachial index; PFWD, pain-free walking distance; PG, parallel-group, nonrandomized; R, randomized; O, open; DB, double blind; CE, clinical evaluation; DS, doppler sonography; SGP, strain-gauge plethysmography; TDM, treadmill; sc, subcutaneously; od, once daily; bid, twice daily.

Table 6 Dosage and administration of parnaparin in different clinical settings

Setting	Dose, UIaXa	Route and frequency
Treatment of CVD, SVT, VPH	3200 to 6400	sbc, od for 20–30 d
DVT prevention in general nonhigh risk surgery	3200	sbc, od 2 h before surgery, then for at least 7 d
DVT prevention in general high risk surgery, or orthopedic surgery	4250	sbc, od 12 h before surgery 12 h after surgery, at least for 10
DVT treatment	12800	iv slow, for 3–5 d sbc,
	6400	tid for at least 7–10 d sbc,
	4250–6400	od for 10–20 d
Unstable angina	6400	sbc, od for 7 d
STEMI	4250	sbc, tid for 7 d
PAOD	6400	sbc, od for 6 m

Abbreviations: CVD, chronic venous diseases; SVT, superficial vein thrombophlebitis; VPH, varicophlebitis; DVT, deep vein thrombosis; STEMI, ST-segment elevation myocardial infarction; PAOD, peripheral arterial occlusive disease; sbc, subcutaneous; od, once-daily; tid, twice-daily; d, days; m, months.

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