Treatment for superficial thrombophlebitis of the leg

Marcello Di Nisio; Iris M Wichers; Saskia Middeldorp

doi:10.1002/14651858.CD004982.pub6

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Fondaparinux versus placebo, Outcome 1 Pulmonary embolism.

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Analysis 1.2

Comparison 1 Fondaparinux versus placebo, Outcome 2 Deep vein thrombosis.

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Analysis 1.3

Comparison 1 Fondaparinux versus placebo, Outcome 3 Deep vein thrombosis or pulmonary embolism.

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Analysis 1.4

Comparison 1 Fondaparinux versus placebo, Outcome 4 Extension of superficial thrombophlebitis.

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Analysis 1.5

Comparison 1 Fondaparinux versus placebo, Outcome 5 Recurrence of superficial thrombophlebitis.

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Analysis 1.6

Comparison 1 Fondaparinux versus placebo, Outcome 6 Mortality.

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Analysis 1.7

Comparison 1 Fondaparinux versus placebo, Outcome 7 Major bleeding.

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Analysis 1.8

Comparison 1 Fondaparinux versus placebo, Outcome 8 Clinically relevant non‐major bleeding.

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Analysis 1.9

Comparison 1 Fondaparinux versus placebo, Outcome 9 Minor bleeding.

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Analysis 1.10

Comparison 1 Fondaparinux versus placebo, Outcome 10 Arterial thromboembolic complication.

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Analysis 1.11

Comparison 1 Fondaparinux versus placebo, Outcome 11 Adverse effects of treatment.

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Analysis 1.12

Comparison 1 Fondaparinux versus placebo, Outcome 12 Non‐fatal serious adverse event.

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Analysis 2.1

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 1 Pulmonary embolism.

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Analysis 2.2

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 2 Deep vein thrombosis.

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Analysis 2.3

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 3 Deep vein thrombosis or pulmonary embolism.

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Analysis 2.4

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 4 Extension of superficial thrombophlebitis.

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Analysis 2.5

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 5 Recurrence of superficial thrombophlebitis.

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Analysis 2.6

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 6 Mortality.

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Analysis 2.7

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 7 Major bleeding.

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Analysis 2.8

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 8 Clinically relevant non‐major bleeding.

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Analysis 2.9

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 9 Minor bleeding.

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Analysis 2.10

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 10 Serious adverse events.

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Analysis 2.11

Comparison 2 Fondaparinux versus rivaroxaban, Outcome 11 Adverse effects of treatment.

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Analysis 3.1

Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 3.2

Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 3.3

Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 3.4

Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 4 Major bleeding.

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Analysis 3.5

Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 5 Heparin‐induced thrombocytopenia.

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Analysis 4.1

Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 4.2

Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 4.3

Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 4.4

Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 4 Major bleeding.

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Analysis 4.5

Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 5 Heparin‐induced thrombocytopenia.

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Analysis 5.1

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 5.2

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 5.3

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.

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Analysis 5.4

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.

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Analysis 5.5

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 5.6

Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 6.1

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 6.2

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 6.3

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.

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Analysis 6.4

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.

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Analysis 6.5

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 6.6

Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 7.1

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 7.2

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 7.3

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.

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Analysis 7.4

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.

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Analysis 7.5

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 7.6

Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.

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Analysis 8.1

Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 1 Symptomatic venous thromboembolism.

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Analysis 8.2

Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 2 Symptomatic pulmonary embolism.

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Analysis 8.3

Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 3 Superficial thrombophlebitis progression into deep vein thrombosis.

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Analysis 8.4

Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 4 Major bleeding.

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Analysis 9.1

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 1 Superficial thrombophlebitis or venous thromboembolism.

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Analysis 9.2

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 2 Venous thromboembolism.

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Analysis 9.3

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 3 Superficial thrombophlebitis.

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Analysis 9.4

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 4 Swelling disappearance.

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Analysis 9.5

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 5 Tenderness disappearance.

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Analysis 9.6

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 6 Pain disappearance.

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Analysis 9.7

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 7 Pitting oedema disappearance.

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Analysis 9.8

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 8 Collateral veins disappearance.

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Analysis 9.9

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 9 Redness disappearance.

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Analysis 9.10

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 10 Palpable cord disappearance.

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Analysis 9.11

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 11 Major bleeding.

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Analysis 9.12

Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 12 Heparin‐induced thrombocytopenia.

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Analysis 10.1

Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 1 Venous thromboembolism.

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Analysis 10.2

Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 10.3

Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 3 Major bleeding.

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Analysis 10.4

Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 4 Complications.

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Analysis 11.1

Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism.

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Analysis 11.2

Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 11.3

Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Major bleeding.

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Analysis 11.4

Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Heparin‐induced thrombocytopenia.

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Analysis 12.1

Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism.

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Analysis 12.2

Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 12.3

Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Major bleeding.

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Analysis 12.4

Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Heparin‐induced thrombocytopenia.

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Analysis 13.1

Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism end‐of‐treatment.

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Analysis 13.2

Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Venous thromboembolism 3‐month follow‐up.

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Analysis 13.3

Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 13.4

Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Major bleeding.

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Analysis 13.5

Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 5 Heparin‐induced thrombocytopenia.

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Analysis 14.1

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 1 Pulmonary embolism.

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Analysis 14.2

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 2 Deep vein thrombosis.

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Analysis 14.3

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 3 Extension of superficial thrombophlebitis.

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Analysis 14.4

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 4 Pain reduction.

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Analysis 14.5

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 5 Hyperaemia reduction.

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Analysis 14.6

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 6 Tenderness reduction.

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Analysis 14.7

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 7 Palpable cord reduction.

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Analysis 14.8

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 8 Mortality.

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Analysis 14.9

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 9 Major bleeding.

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Analysis 14.10

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 10 Minor bleeding.

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Analysis 14.11

Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 11 Adverse events.

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Analysis 15.1

Comparison 15 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.

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Analysis 15.2

Comparison 15 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 16.1

Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 1 Deep vein thrombosis.

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Analysis 16.2

Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 2 Participants with thrombus at 21 days.

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Analysis 16.3

Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 3 Allergic reaction or elevated sedimentation rate.

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$Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 1 Incidence of venous thromboembolism.$

Analysis 17.1

Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 1 Incidence of venous thromboembolism.

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$Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.$

Analysis 17.2

Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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$Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 3 Major bleeding.$

Analysis 17.3

Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 3 Major bleeding.

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$Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 4 Heparin‐induced thrombocytopenia.$

Analysis 17.4

Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 4 Heparin‐induced thrombocytopenia.

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Analysis 18.1

Comparison 18 Heparin calcium plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.

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Analysis 19.1

Comparison 19 Heparin subcutaneous (sc) versus defibrotide, Outcome 1 Decrease in the analogue score.

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Analysis 19.2

Comparison 19 Heparin subcutaneous (sc) versus defibrotide, Outcome 2 Adverse effects of treatment.

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Analysis 20.1

Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 1 Venous thromboembolism.

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Analysis 20.2

Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 20.3

Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 3 Major bleeding.

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Analysis 20.4

Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 4 Heparin‐induced thrombocytopenia.

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Analysis 21.1

Comparison 21 Indomethacin versus placebo, Outcome 1 Adverse effects.

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Analysis 22.1

Comparison 22 Nimesulide versus diclofenac sodium, Outcome 1 Gastric pain.

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Analysis 23.1

Comparison 23 Essaven gel versus placebo, Outcome 1 Intolerance.

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Analysis 24.1

Comparison 24 Thrombectomy plus venoruton plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.

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Analysis 25.1

Comparison 25 Thrombectomy plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.

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Analysis 26.1

Comparison 26 Ligation plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.

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Analysis 26.2

Comparison 26 Ligation plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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$Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.$

Analysis 27.1

Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.

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$Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.$

Analysis 27.2

Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 28.1

Comparison 28 Oral vasotonin versus placebo, Outcome 1 Cured or substantially better.

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Analysis 28.2

Comparison 28 Oral vasotonin versus placebo, Outcome 2 Poor tolerability.

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Analysis 29.1

Comparison 29 Elastic compression bandage (ECB) plus venoruton versus ECB alone, Outcome 1 Deep vein thrombosis.

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Analysis 30.1

Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 1 Redness disappearance.

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Analysis 30.2

Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 2 Pain disappearance.

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Analysis 30.3

Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 3 Disappearance of itching.

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Analysis 30.4

Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 4 Oedema improvement.

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Analysis 30.5

Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 5 Trophism improvement.

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Analysis 31.1

Comparison 31 Oxyphenbutazone versus placebo, Outcome 1 Tenderness improvement.

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Analysis 32.1

Comparison 32 Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.

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Analysis 32.2

Comparison 32 Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 33.1

Comparison 33 Stripping plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.

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Analysis 33.2

Comparison 33 Stripping plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.

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Analysis 34.1

Comparison 34 Enzyme therapy versus placebo, Outcome 1 Pain reduction.

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Analysis 34.2

Comparison 34 Enzyme therapy versus placebo, Outcome 2 Responders.

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Analysis 35.1

Comparison 35 Desmin intramuscular (im) 200 versus desmin 100, Outcome 1 Adverse events.

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Analysis 35.2

Comparison 35 Desmin intramuscular (im) 200 versus desmin 100, Outcome 2 Adverse drug reactions.

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Analysis 36.1

Comparison 36 Desmin subcutaneous (sc) 2 × 100 versus desmin 100, Outcome 1 Adverse events.

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Analysis 36.2

Comparison 36 Desmin subcutaneous (sc) 2 × 100 versus desmin 100, Outcome 2 Adverse drug reactions.

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Analysis 37.1

Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 1 Pain (VAS, cm) at 3 weeks.

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Analysis 37.2

Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 2 Skin erythema (cm²) at 3 weeks.

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Analysis 37.3

Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 3 SF‐36 physical score at 3 weeks.

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Analysis 37.4

Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 4 SF‐36 mental score at 3 weeks.

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Summary of findings for the main comparison. Fondaparinux compared to placebo for superficial thrombophlebitis of the leg

Fondaparinux compared to placebo for superficial thrombophlebitis of the leg
Patient or population: people with ST of the leg Settings: hospitalised or non‐hospitalised Intervention: fondaparinux Comparison: placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Fondaparinux
Symptomatic VTE Ventilation‐perfusion scanning, helical computed tomography, pulmonary angiography, autopsy, ultrasonography, or venography Follow‐up: 77 days	13 per 1000	2 per 1000 (1 to 7)	RR 0.15 (0.04 to 0.5)	3002 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Major bleeding Follow‐up: 77 days	1 per 1000	1 per 1000 (0 to 11)	RR 0.99 (0.06 to 15.86)	2987 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Extension of ST Ultrasonography Follow‐up: 77 days	34 per 1000	3 per 1000 (1 to 7)	RR 0.08 (0.03 to 0.22)	3002 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Recurrence of ST Ultrasonography Follow‐up: 77 days	16 per 1000	3 per 1000 (1 to 9)	RR 0.21 (0.08 to 0.54)	3002 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Mortality Follow‐up: 77 days	1 per 1000	1 per 1000 (0 to 15)	RR 2 (0.18 to 22)	3002 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Minor bleeding Follow‐up: 77 days	4 per 1000	6 per 1000 (2 to 17)	RR 1.49 (0.53 to 4.17)	2987 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
Adverse effects of treatment Follow‐up: 77 days	33 per 1000	37 per 1000 (26 to 54)	RR 1.13 (0.78 to 1.65)	2987 (1 study)	⊕⊕⊕⊝ Moderate¹	‐
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; ST: superficial thrombophlebitis; VTE: venous thromboembolism.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Evidence downgraded one level for imprecision due to a low number of events.

Summary of findings for the main comparison. Fondaparinux compared to placebo for superficial thrombophlebitis of the leg

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Summary of findings 2. Prophylactic LMWH versus placebo for superficial thrombophlebitis of the leg

Prophylactic LMWH versus placebo for superficial thrombophlebitis of the leg
Patient or population: people with ST of the leg Settings: hospitalised and non‐hospitalised Intervention: prophylactic LMWH versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Prophylactic LMWH
Symptomatic VTE Follow‐up: 97 days	45 per 1000	54 per 1000 (17 to 174)	RR 1.22 (0.38 to 3.89)	222 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Major bleeding Follow‐up: 97 days	See comment	See comment	Not estimable	222 (1 study)	⊕⊕⊝⊝ Low^1,2	0 episodes of major bleeding
Extension or recurrence (or both) of ST Follow‐up: 97 days	330 per 1000	145 per 1000 (86 to 244)	RR 0.44 (0.26 to 0.74)	222 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Mortality	See comment	See comment	See comment	‐	See comment	Data not available
Minor bleeding	See comment	See comment	See comment	‐	See comment	Data not available
Adverse effects of treatment	See comment	See comment	See comment	‐	See comment	Data not available
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LMWH: low molecular weight heparin; RR: risk ratio; ST: superficial thrombophlebitis; VTE: venous thromboembolism.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Evidence downgraded one level due to unclear random sequence generation and incomplete outcome data. ²Evidence downgraded one level for imprecision due to a low number of events.

Summary of findings 2. Prophylactic LMWH versus placebo for superficial thrombophlebitis of the leg

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Summary of findings 3. Therapeutic LMWH versus placebo for superficial thrombophlebitis of the leg

Therapeutic LMWH versus placebo for superficial thrombophlebitis of the leg
Patient or population: people with ST of the leg Settings: hospitalised and non‐hospitalised Intervention: therapeutic LMWH versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Therapeutic LMWH
Symptomatic VTE Follow‐up: 97 days	45 per 1000	38 per 1000 (10 to 137)	RR 0.85 (0.23 to 3.06)	218 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Major bleeding Follow‐up: 97 days	See comment	See comment	Not estimable	218 (1 study)	⊕⊕⊝⊝ Low^1,2	No episodes of major bleeding
Extension or recurrence (or both) of ST Follow‐up: 97 days	330 per 1000	152 per 1000 (89 to 254)	RR 0.46 (0.27 to 0.77)	218 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Mortality	See comment	See comment	See comment	‐	See comment	Data not available
Minor bleeding	See comment	See comment	See comment	‐	See comment	Data not available
Adverse effects of treatment	See comment	See comment	See comment	‐	See comment	Data not available
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LMWH: low molecular weight heparin; RR: risk ratio; ST: superficial thrombophlebitis; VTE: venous thromboembolism.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Evidence downgraded one level due to an unclear random sequence generation and incomplete outcome data. ²Evidence downgraded one level for imprecision due to a low number of events.

Summary of findings 3. Therapeutic LMWH versus placebo for superficial thrombophlebitis of the leg

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Summary of findings 4. NSAIDs versus placebo for superficial thrombophlebitis of the leg

NSAIDs versus placebo for superficial thrombophlebitis of the leg
Patient or population: people with superficial thrombophlebitis of the leg Settings: hospitalised and non‐hospitalised Intervention: NSAIDs versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	NSAIDs
Symptomatic VTE Follow‐up: 97 days	45 per 1000	41 per 1000 (11 to 146)	RR 0.91 (0.25 to 3.28)	211 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Major bleeding Follow‐up: 97 days	See comment	See comment	Not estimable	211 (1 study)	⊕⊕⊝⊝ Low^1,2	0 episodes of major bleeding
Extension or recurrence (or both) of ST Follow‐up: 97 days	330 per 1000	152 per 1000 (89 to 258)	RR 0.46 (0.27 to 0.78)	211 (1 study)	⊕⊕⊝⊝ Low^1,2	‐
Mortality	See comment	See comment	See comment	‐	See comment	Data not available
Minor bleeding	See comment	See comment	See comment	‐	See comment	Data not available
Adverse effects of treatment	See comment	See comment	See comment	‐	See comment	Data not available
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NSAIDs: non‐steroidal anti‐inflammatory drugs; RR: risk ratio; ST: superficial thrombophlebitis; VTE: venous thromboembolism.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹Evidence downgraded one level due to an unclear random sequence generation and incomplete outcome data. ²Evidence downgraded one level for imprecision due to a low number of events.

Summary of findings 4. NSAIDs versus placebo for superficial thrombophlebitis of the leg

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Comparison 1. Fondaparinux versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Deep vein thrombosis or pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Extension of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Recurrence of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Mortality Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8 Clinically relevant non‐major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9 Minor bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10 Arterial thromboembolic complication Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11 Adverse effects of treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

12 Non‐fatal serious adverse event Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 1. Fondaparinux versus placebo

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Comparison 2. Fondaparinux versus rivaroxaban

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Deep vein thrombosis or pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Extension of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Recurrence of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Mortality Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8 Clinically relevant non‐major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9 Minor bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10 Serious adverse events Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11 Adverse effects of treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Fondaparinux versus rivaroxaban

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Comparison 3. Prophylactic low molecular weight heparin (LMWH) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 3. Prophylactic low molecular weight heparin (LMWH) versus placebo

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Comparison 4. Therapeutic low molecular weight heparin (LMWH) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 4. Therapeutic low molecular weight heparin (LMWH) versus placebo

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Comparison 5. Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic deep vein thrombosis end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Symptomatic deep vein thrombosis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Extension of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Recurrence of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH

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Comparison 6. Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic deep vein thrombosis end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Symptomatic deep vein thrombosis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Extension of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Recurrence of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 6. Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH

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Comparison 7. Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic deep vein thrombosis end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Symptomatic deep vein thrombosis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Extension of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Recurrence of superficial thrombophlebitis 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 7. Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH

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Comparison 8. Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Symptomatic pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Superficial thrombophlebitis progression into deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 8. Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH

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Comparison 9. Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Superficial thrombophlebitis or venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism Show forest plot	2	238	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.10, 2.72]

3 Superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Swelling disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Tenderness disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Pain disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7 Pitting oedema disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

8 Collateral veins disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9 Redness disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10 Palpable cord disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11 Major bleeding Show forest plot	2	238	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

12 Heparin‐induced thrombocytopenia Show forest plot	2	238	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.07, 16.11]

Comparison 9. Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH

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Comparison 10. Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Complications Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 10. Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection

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Comparison 11. Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	2	278	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.24, 3.63]

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	3	331	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.58, 1.78]

3 Major bleeding Show forest plot	3	335	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

4 Heparin‐induced thrombocytopenia Show forest plot	2	278	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 11. Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

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Comparison 12. Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 12. Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

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Comparison 13. Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism end‐of‐treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Venous thromboembolism 3‐month follow‐up Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 13. Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs)

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Comparison 14. Low molecular weight heparin (LMWH) versus LMWH plus acemetacin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pulmonary embolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Extension of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Pain reduction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5 Hyperaemia reduction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6 Tenderness reduction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7 Palpable cord reduction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8 Mortality Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10 Minor bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11 Adverse events Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 14. Low molecular weight heparin (LMWH) versus LMWH plus acemetacin

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Comparison 15. Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 15. Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone

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Comparison 16. Low molecular weight heparin (LMWH) versus heparin spray gel

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deep vein thrombosis Show forest plot	2	83	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.03, 2.70]

2 Participants with thrombus at 21 days Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Allergic reaction or elevated sedimentation rate Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 16. Low molecular weight heparin (LMWH) versus heparin spray gel

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Comparison 17. High‐dose unfractionated heparin (UFH) versus low‐dose UFH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 17. High‐dose unfractionated heparin (UFH) versus low‐dose UFH

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Comparison 18. Heparin calcium plus elastic compression bandage (ECB) versus ECB alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 18. Heparin calcium plus elastic compression bandage (ECB) versus ECB alone

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Comparison 19. Heparin subcutaneous (sc) versus defibrotide

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Decrease in the analogue score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Adverse effects of treatment Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 19. Heparin subcutaneous (sc) versus defibrotide

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Comparison 20. Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Major bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Heparin‐induced thrombocytopenia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 20. Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo

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Comparison 21. Indomethacin versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 21. Indomethacin versus placebo

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Comparison 22. Nimesulide versus diclofenac sodium

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Gastric pain Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 22. Nimesulide versus diclofenac sodium

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Comparison 23. Essaven gel versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Intolerance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 23. Essaven gel versus placebo

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Comparison 24. Thrombectomy plus venoruton plus elastic compression bandage (ECB) versus ECB alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 24. Thrombectomy plus venoruton plus elastic compression bandage (ECB) versus ECB alone

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Comparison 25. Thrombectomy plus elastic compression bandage (ECB) versus ECB alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 25. Thrombectomy plus elastic compression bandage (ECB) versus ECB alone

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Comparison 26. Ligation plus elastic compression stockings (ECS) versus ECS alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 26. Ligation plus elastic compression stockings (ECS) versus ECS alone

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Comparison 27. Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 27. Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone

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Comparison 28. Oral vasotonin versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cured or substantially better Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Poor tolerability Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 28. Oral vasotonin versus placebo

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Comparison 29. Elastic compression bandage (ECB) plus venoruton versus ECB alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deep vein thrombosis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 29. Elastic compression bandage (ECB) plus venoruton versus ECB alone

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Comparison 30. Oral heparansulphate versus oral sulodexide

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Redness disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Pain disappearance Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Disappearance of itching Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Oedema improvement Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Trophism improvement Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 30. Oral heparansulphate versus oral sulodexide

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Comparison 31. Oxyphenbutazone versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tenderness improvement Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 31. Oxyphenbutazone versus placebo

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Comparison 32. Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 32. Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone

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Comparison 33. Stripping plus elastic compression stockings (ECS) versus ECS alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Venous thromboembolism Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Extension or recurrence (or both) of superficial thrombophlebitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 33. Stripping plus elastic compression stockings (ECS) versus ECS alone

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Comparison 34. Enzyme therapy versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain reduction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Responders Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 34. Enzyme therapy versus placebo

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Comparison 35. Desmin intramuscular (im) 200 versus desmin 100

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adverse events Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Adverse drug reactions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 35. Desmin intramuscular (im) 200 versus desmin 100

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Comparison 36. Desmin subcutaneous (sc) 2 × 100 versus desmin 100

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Adverse events Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Adverse drug reactions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 36. Desmin subcutaneous (sc) 2 × 100 versus desmin 100

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Comparison 37. Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pain (VAS, cm) at 3 weeks Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Skin erythema (cm²) at 3 weeks Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 SF‐36 physical score at 3 weeks Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4 SF‐36 mental score at 3 weeks Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 37. Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH

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