Limited evidence on persistence with anticoagulants, and its effect on the risk of recurrence of venous thromboembolism: a systematic review of observational studies

Figures & data

Figure 1 PRISMA flow diagram.

Abbreviations: PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; VTE, venous thromboembolism.

Table 1 Characteristics of studies included in the review

Source and year	Study design	Country	Database	Number of participants	Age, years, mean (SD)	Female, %	Measure	Technique	Criterion for nonpersistence	Condition	Treatment	Persistence, % (n/N)			Risk of VTE recurrence
												3 months	6 months	12 months
Beyer-Westendorf et al^Citation27 (2013)a	Prospective registry	Germany	NOAC registry	233	63.5	54.9	Discontinuation	Phone visits	NA	Acute VTE	DOAC (rivaroxaban)	NA	61.5	NA	NA
Beyer-Westendorf et al^Citation28 (2013)a	Prospective registry	Germany	NOAC registry	168	62.5	NA	Discontinuation	Phone visits	NA	Chronic VTE	DOAC (rivaroxaban)	NA	88.5	NA	NA
Cohen et al^Citation26 (2013)a	Retrospective cohort	UK	CPRD	8,504 (7,676 in analysis)	63.5	53.6	Persistence	Prescription fills	Gap of 56 days	VTE (complete cohort)	VKA (unspecified)	77.4	50.3	11.4	NA
–	–	–		Subgroup (3,130)	–	–	Persistence	Prescription fills	Gap of 56 days	Provoked VTE (noncancer)	VKA (unspecified)	76.8	49.0	10.3	NA
–	–	–		Subgroup (4,546)	–	–	Persistence	Prescription fills	Gap of 56 days	Unprovoked VTE	VKA (unspecified)	77.8	51.1	11.9	NA
Gelbricht et al^Citation30 (2012)a	Prospective registry	Germany	NOAC registry	105	62.5 (±18.2)	55.2	Discontinuation	Phone visits	NA	Acute VTE	DOAC (rivaroxaban)	64 (32/50)	41.7 (5/12)	NA	NA
Koehler et al^Citation29(2012)a	Prospective registry	Germany	NOAC registry	126	64.4 (±15.1)	42.1	Discontinuation	Phone visits	NA	Extended VTE treatment	DOAC (rivaroxaban)	94.2 (81/86)	85.2 (23/27)	NA	NA
Köhler et al^Citation25 (2013)a	Prospective registry	Germany	NOAC registry	72	67.3	55.6	Discontinuation	Phone visits	NA	Acute PE	DOAC (rivaroxaban)	94 (63/67)	80 (44/55)	78.9 (15/19)	NA
Tagalakis et al^Citation24 (2013)a	Retrospective cohort	Canada (Quebec)	Administrative health care databases	40,776 (20,806 in analysis)	.60 (78% ofthe cohort)	58.3	Persistence	Prescription fills	NA	VTE (complete cohort)	VKA (unspecified)	87.6	62.2	21.0	NA
–	–	–		Subgroup (13,041)	–	–	Persistence	Prescription fills	NA	Provoked VTE (noncancer)	VKA (unspecified)	86.9	59.5	19.9	NA
–	–	–		Subgroup (7,765)	–	–	Persistence	Prescription fills	NA	Unprovoked VTE	VKA (unspecified)	88.8	66.8	22.9	NA
Chen et al^Citation19 (2013)c	Retrospective cohort	USA	MarketScan database	8,040	61.2 (±14.8)	40.6	Persistence	Prescription fills	Gap of 90 days	VTE	VKA (warfarin)	NA	NA	49.3	HRd: 1.48; 95% CI: 1.09–2.01
Deitelzweig et al^Citation21 (2010)c	Retrospective cohort	USA	Integrated Healthcare Information Services	8,380	52	51.1	Persistence	Prescription fills	Gap between expected and observed refill date	VTE	VKA (warfarin)	87.7	NA	36.6	HRb: 1.45; 95% CI: 1.18–1.77
Reardon et al^Citation20 (2012)c	Retrospective cohort	USA	AnalytiCare LTC database	489	80 (median)	70	Persistence	Prescription fills	Gap of 37 days	VTE	VKA (warfarin)	72	41	16	NA
Kaatz et al^Citation22 (2014)c	Retrospective cohort	USA	HealthCore Integrated Research Database	2,002	57 (±15)	47.7	Persistence	Prescription fills	Gap of 60 days and INR test every 42 days	VTE (complete cohort)	Multiplee	78.9	56.6	31.6	NA
–	–	–	–	Subgroup (758)	–	–	–	–	–	Provoked VTE (incl cancer related)	–	NA	NA	NA	NA
–	–	–	–	Subgroup (1,244)	–	–	–	–	–	Unprovoked VTE	–	NA	NA	NA	NA
Xie et al^Citation23 (2015)c	Retrospective cohort	USA	MarketScan database	37,664	60.2	41.3	Persistence	Prescription fills	Gap of 45 days after end date of previous prescription	Unprovoked VTE	VKA (warfarin)	78.6 (25,750/32,753)	57.2 (15,919/27,812)	29.9 (6,325/21,163)	NA

Notes:

a Conference abstract;

b risk of recurrence for patients with discontinuation of warfarin within 3 months compared with discontinuation after ≥3 months;

c full-text article;

d risk of recurrence after completing 1 year of therapy for patients nonpersistent compared with persistent during 1 year of anticoagulant therapy;

e 93% warfarin users and 7% users of enoxaparin, heparin, tinzaparin, dalteparin, or fondaparinux.

Abbreviations: CI, confidence interval; CPRD, clinical practice research datalink; DOAC, direct oral anticoagulant; HR, hazard ratio; NA, not available; NOAC, novel oral anticoagulants; PE, pulmonary embolism; SD, standard deviation; VKA, vitamin K antagonist; VTE, venous thromboembolism; INR, international normalized ratio.

Figure 2 Pooled proportion of patients persistent with anticoagulation treatment.

Notes: (A) 3 months. (B) 6 months. (C) 12 months.
Abbreviation: CI, confidence interval.

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