|Year : 2019 | Volume
| Issue : 4 | Page : 274-277
Quality of life after catheter-directed thrombolysis and standard anticoagulation for iliofemoral deep-vein thrombosis
Jithin Jagan Sebastian, MK Ayyappan, Pranay Pawar, Kapil Mathur, Radhakrishnan Raju, Naveen Rajendra
Department of Vascular Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
|Date of Submission||14-Sep-2019|
|Date of Decision||19-Nov-2019|
|Date of Acceptance||21-Oct-2019|
|Date of Web Publication||20-Dec-2019|
Dr. M K Ayyappan
Department of Vascular Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: Acute ilio-femoral deep-vein thrombosis (IFDVT) is associated with the morbidity of postthrombotic syndrome (PTS). There are many younger patients presenting with IFDVT in India. Not much is known of the incidence of PTS in these patients and the quality of life (QOL) after treatment with catheter-directed thrombolysis (CDT) or standard anticoagulation in these patients. Materials and Methods: A prospective, nonrandomized, case–control study was conducted on patients who presented with acute, primary IFDVT (<14 days) to a tertiary care hospital. Patients with iliac and femoral deep vein thrombosis, confirmed by computed tomography venogram, were studied. PTS was assessed by the Villalta score. Disease-specific QOL was measured by Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Symptoms and health-related QOL by the EuroQOL (EQ)-5D questionnaires. Results: A total of 100 patients with acute IFDVT were followed up for a mean of 33 months. Villalta score and QOL scores for 49 CDT patients and 51 patients managed conservatively were calculated. Demographics were comparable between the groups. PTS developed in 29% of patients (18% vs. 39%, P = 0.035). The QOL calculated by VEINES-Sym/QOL (mean 74.29 vs. 70.14, P = 0.006) and EQ-5D (mean 0.50 vs. 1.76, P = 0.004) showed significant difference. Both scores were significant for PTS versus no PTS (P ≤ 0.001). Absolute risk reduction between the groups was 20.8% and the number needed to treat was one in five patients. Conclusion: CDT reduces the incidence of PTS and improves the health-related and disease-specific QOL in a younger population of patients with acute IFDVT, compared to standard treatment with anticoagulation alone.
Keywords: Catheter-directed thrombolysis, ileo-femoral deep-vein thrombosis, postthrombotic syndrome, quality of life
|How to cite this article:|
Sebastian JJ, Ayyappan M K, Pawar P, Mathur K, Raju R, Rajendra N. Quality of life after catheter-directed thrombolysis and standard anticoagulation for iliofemoral deep-vein thrombosis. Indian J Vasc Endovasc Surg 2019;6:274-7
|How to cite this URL:|
Sebastian JJ, Ayyappan M K, Pawar P, Mathur K, Raju R, Rajendra N. Quality of life after catheter-directed thrombolysis and standard anticoagulation for iliofemoral deep-vein thrombosis. Indian J Vasc Endovasc Surg [serial online] 2019 [cited 2020 Jun 4];6:274-7. Available from: http://www.indjvascsurg.org/text.asp?2019/6/4/274/273601
| Introduction|| |
Deep-vein thrombosis (DVT) is a burgeoning problem in India with a predominant younger age at presentation. The incidence of DVT is 17.46/10,000 hospital admissions. Nearly 66% of these patients present with acute DVT and 88% of acute DVT patients have proximal iliofemoral DVT (IFDVT). The patients presenting with DVT are younger with a mean age of 49 years. Most patients go on to develop postthrombotic syndrome (PTS) on account of a late presentation or financial constraints in treating the DVT. PTS occurs in 23%–60% of DVT cases with higher incidence among proximal DVT patients. The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) and catheter directed venous thrombolysis in acute iliofemoral vein thrombosis (CaVenT) trials have provided strong evidence regarding the use of CDT in DVT. These trials have their pitfalls whereby they included femoro-popliteal DVT. Nevertheless, they have pointed the way to guiding interventions in IFDVT patients. Little is known about the incidence of PTS in India or the quality of life (QOL) of these patients with or without treatment. PTS is the single main determinant of the QOL as pointed out by the CaVenT trial. This study aims to determine the incidence of PTS in CDT patients and its effect on the health-related and disease-specific QOL in these patients, compared to standard anticoagulation.
| Materials and Methods|| |
This was a prospective, nonrandomized, case–control study conducted at a tertiary care hospital in India. The study period was for 4 years from 2015 to 2018. The study was carried out to compare the incidence of PTS in patients with proximal IFDVT treated by standard anticoagulation and CDT. The QOL of these patients was assessed to determine the long-term effects of these two treatment options on patient life.
Inclusion and exclusion
Patients aged 18–75 years with first-time DVT were included in the study. Patients with IFDVT, objectively confirmed by computed tomography (CT) venogram, were studied. Patients with recurrent DVT or those presenting to the hospital 14 days after symptom onset, were excluded from the study. The study was approved by the hospital's ethics committee. The patients who underwent CDT were studied and those not willing or not affordable for CDT formed the control group. Appropriate consent was taken from these patients for the study and follow-up. Age >75 years, life expectancy <1 year, or those not willing to participate in the long follow-up process were excluded from the study. Patients with contraindications to thrombolytic therapy with a history of recent stroke (<3 months), gastrointestinal bleeding, severe hypertension, pregnancy (till 7 days postpartum), or major surgery within 6 weeks were excluded from the study. Those with severe renal failure (creatinine clearance <30 ml/min), active malignancy, and recent (<7 days) history of thrombolytic therapy were also excluded from the study.
All patients with CT scan confirmed IFDVT were offered the option of CDT. All patients were started on unfractionated or low-molecular-weight heparin (LMWH) at presentation as per our institutional protocols. The thrombus load of these patients was calculated based on the segments involved on CT venogram, giving one point each for inferior vena cava (IVC), common iliac vein, external iliac vein, common femoral vein, proximal superficial femoral vein, distal superficial femoral vein, popliteal vein, long saphenous vein, and short saphenous vein.
Patients willing for CDT were electively posted for venogram and catheter insertion. The anticoagulation was stopped 8 h prior to surgery. The patients underwent an ultrasound-guided puncture of the appropriate vein usually popliteal vein or mid-superficial femoral vein under local anesthesia. A single dose of 5000 units of unfractionated heparin was given after puncture. A venogram was obtained, and a multi-hole infusion catheter was inserted till the proximal extent of the thrombus. A bolus dose of 3 mg of alteplase (Actilyse; Boehringer-Ingelheim, Ingelheim am Rhein, Germany) was administered through the catheter. Alteplase infusion at 0.01 mg/kg/h was started through the catheter. If extensive femoro-popliteal involvement was present on venogram, the alteplase was started in two divided doses both in the catheter and the access sheath. Unfractionated heparin infusion was started at 15U/kg/h either in the access sheath or through an intravenous line.
Treatment was continued in the ward with 6th hourly monitoring of serum fibrinogen and activated partial thromboplastin time (APTT). Thrombolysis was stopped if the fibrinogen levels fell below 100 mg/dl. An APTT of 1.2–1.7 times was maintained by adjusting the heparin dosage 6th hourly. The infusion was continued for a day following which a check venogram was carried out. If the venogram shows complete resolution of thrombus from the ilio-femoral segment, the thrombolysis was discontinued and catheter was removed. Stenting and angioplasty were carried out if compression was noted at the common iliac segment. If the thrombus resolution was not adequate (defined as <50% iliofemoral thrombus resolution), the patient was put on additional thrombolysis for a day and stenting was carried out after 4 weeks. All patients were started on LMWH post procedure and discharged on oral acenocoumarol for 3 months. Patients not willing for the procedure were started on oral acenocoumarol and dose was titrated to maintain an international normalized ratio of 2–3 for 3 months.
Patients were followed up by clinical assessment at 1 week, 6 months, and then yearly thereafter. Only patients with a minimum follow-up of 1 year were included in the study. Patients were evaluated for the development of PTS by the Villalta score. A Villalta score of 5 and more was considered significant. Those with ulceration were documented. Health-related QOL was assessed by the generic EuroQOL (EQ)-5D and the disease-specific QOL measure by the Venous Insufficiency Epidemiological and Economic Study (VEINES-QOL/sym). Villalta score taken with the VEINES Sym/QOL has been shown to be the best way to identify PTS. Thrombophilia screening was carried out after stopping oral anticoagulants at 3 months.
A pilot study of thirty patients was undertaken which showed an incidence of PTS of 26% at 2 years. Hence, a sample size of 100 patients was required for a study with 5% alpha error and 90% power. Comparison between the two groups for dichotomous variables was carried out by two-sided Chi-square test. When comparing continuous variables, a two-sided t-test was used, provided that the distributions were sufficiently close to the normal distribution. Otherwise, a two-sided Mann–Whitney test was used. Findings with P < 0.05 were considered statistically significant.
| Results|| |
The study was conducted analyzing patients with IFDVT between January 2015 and October 2018. A total of 189 patients presented with acute (<14 days) IFDVT to our hospital. Eighty patients underwent CDT and another 109 patients underwent standard treatment. A total of 18 deaths were present during the study period, which were excluded, and 20 patients were lost to follow-up. Fifty-one patients were excluded as they did not fit the inclusion criteria. The patients who were excluded had heart failure (5 patients), active malignancy (13 patients), pregnancy (2 patients), gastrointestinal bleeding (1 patients), stroke (8 patients), recurrence (3 patients), or recent surgery (19 patients). A total of 100 patients were followed up for a mean of 33 months. The profile of study is depicted in [Figure 1]. A total of 49 patients undergoing CDT were compared with standard treatment.
The demographics of the patient population are comparable and are shown in [Table 1]. The duration of symptoms and the time to treatment were different between the two groups. There was a difference in the thrombus load between the two groups. Age, sex, side, body mass index (BMI) risk factors, and provoked or unprovoked status were similar between the groups. Nearly 19.6% of the patients presented with breathlessness along with leg swelling as the primary symptom. The incidence of pulmonary embolism was 21%. The follow-up duration of these patients was a mean of 36 months for the CDT group compared with 29 months for the anticoagulation group. All patients in both groups were compliant with medication for a period of 3 months.
The mean duration of treatment was 3.64 days (3–5 days) for the CDT group. The mean dosage of fibrinolytic used was 33.2 mg (25–47 mg). The mean duration of lysis was 42.4 h (34–72 h). The duration of lytic (P = 0.115) or the time to undergo CDT did not correlate with the incidence of PTS. The incidence of pulmonary embolism and recurrent thromboembolism was also similar between the groups.
The incidence of mild-to-severe PTS (score >5) in the group with CDT was 18% (9/49 patients). Patients who underwent standard anticoagulation had a PTS incidence of 39% (20/51). PTS in patients who completed 2-year follow-up (N = 81) was statistically significant (P = 0.035). Ulcers were present in two patients in the standard treatment group compared to one patient in the CDT group.
The QOL of these patients was also statistically significantly affected as measured by the EQ-5D (P = 0.004) and VEINS QOL/SYM score (P = 0.006). Almost 22% of the patients underwent stenting during check venogram in view of significant iliac vein compression. IVC filter was deployed in 6% of patients.
| Discussion|| |
In India, DVT presents in a younger patient population (mean age: 46–49 years) compared to the Western population as seen in several earlier studies.,, There is a need to assess treatment results and the QOL after treatment of IFDVT in this younger population. The only study to previously address this issue was done by Srinivas et al., which showed an incidence of 20% PTS among the CDT patients and 77% among those on anticoagulation. There has been a change in the treatment paradigm since then with the publication of the two landmark trials (ATTRACT and CaVenT). Tissue plasminogen activators are also now readily available which have been shown to have less bleeding complication than streptokinase for CDT.
The risk factors for the development of PTS and those affecting the QOL of IFDVT patients have been reported by Kahn et al., Based on the above-mentioned studies, and the various guidelines by the American College of Chest Physicians and the Society of Interventional Radiology, we chose patients with iliac and femoral involvement of DVT and excluded all proximal-femoral DVT. The more proximal the DVT, the higher the incidence of PTS and worse the QOL if not treated. Patients with acute symptoms (<14 days) were studied in contrast to most other studies,, which included a subacute group. Patients presenting after 14 days of symptom onset usually land up with suboptimal lysis, hence were excluded. The risk factors of age, sex, BMI, and time to treatment were comparable between the groups. The thrombus load was higher in the CDT group, as usually more extensive DVT patients are more symptomatic warranting catheter-directed treatment. This aspect of treatment corresponds to real-world practice. CT venogram has a sensitivity of 95.9% and a specificity of 95.2% in detecting proximal thrombus as shown by Thomas et al.
The incidence of PTS in our study was 18% in the CDT group compared to 39% in the control group at 2 years. The incidence is much lesser compared to the previous study by Srinivas et al. Compared to the CaVenT and ATTRACT trials, the incidence is much lesser, most probably due to the selection of more proximal DVT and patients with acute symptoms. There is an absolute risk reduction of 20.8%. The number needed to treat is one in five patients which is much lesser than the CaVenT trial. This is also probably due to the younger patient population presenting with DVT compared to other studies.,,
The QOL of these patients was affected by the development of PTS (P = 0.001). The health-related QOL of these patients and the disease-specific QOL of these patients were significantly affected as shown in [Table 2]. This echoes the results of the study by Comerota et al. in 2000. The VEINES Sym/QOL score taken with Villalta scores showed significance between the patient populations, confirming the incidence of PTS in these patients. Most of these patients were found to be anxious about their symptoms post treatment, which affected their overall QOL.
|Table 2: Incidence of postthrombotic syndrome and quality of life at 2 years|
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IVC filter was deployed in only patients with contraindication to anticoagulation as pointed out by Vedantham et al. and Watson et al. There was no difference in the incidence of recurrent DVT between the groups on follow-up similar to various meta-analyses.,, There are some limitations to the study mostly in the form of lack of randomization. This, however, conforms to real-world practices in the use of CDT.
| Conclusion|| |
CDT reduces the incidence of PTS and improves the health-related and disease-specific QOL in the younger population of patients with acute IFDVT, compared to standard treatment with anticoagulation alone. The number needed to treat to prevent PTS is one in five patients in this patient group.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Lee AD, Stephen E, Agarwal S, Premkumar P. Venous thrombo-embolism in India. Eur J Vasc Endovasc Surg 2009;37:482-5.
Pawar P, Ayyappan MK, Jagan J, Rajendra N, Mathur K, Raju R. Analysis of patients with venous thromboembolism in a multi-specialty tertiary hospital in South India. Indian J Vasc Endovasc Surg 2019;6:[In press].
Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis 2009;28:465-76.
Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al.
Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N
Engl J Med 2017;377:2240-52.
Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, et al.
Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): A randomised controlled trial. Lancet 2012;379:31-8.
Soosainathan A, Moore HM, Gohel MS, Davies AH. Scoring systems for the post-thrombotic syndrome. J Vasc Surg 2013;57:254-61.
Kamerkar DR, John MJ, Desai SC, Dsilva LC, Joglekar SJ. Arrive: A retrospective registry of Indian patients with venous thromboembolism. Indian J Crit Care Med 2016;20:150-8.
] [Full text]
Pinjala R; ENDORSE-India investigators. Venous thromboembolism risk & prophylaxis in the acute hospital care setting (ENDORSE), a multinational cross-sectional study: Results from the Indian subset data. Indian J Med Res 2012;136:60-7. [Full text]
Srinivas BC, Patra S, Nagesh CM, Reddy B, Manjunath CN. Catheter-directed thrombolysis along with mechanical thromboaspiration versus anticoagulation alone in the management of lower limb deep venous thrombosis-A comparative study. Int J Angiol 2014;23:247-54.
Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ, et al.
Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008;149:698-707.
Kahn SR, Shbaklo H, Lamping DL, Holcroft CA, Shrier I, Miron MJ, et al.
Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost 2008;6:1105-12.
Guyatt GH, Akl EA, Crowther M, Schünemann HJ, Gutterman DD, Lewis SZ, et al.
Introduction to the ninth edition: Antithrombotic therapy and prevention of thrombosis, 9th
ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:48S-52S.
Vedantham S, Thorpe PE, Cardella JF, Grassi CJ, Patel NH, Ferral H, et al.
Quality improvement guidelines for the treatment of lower extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol 2006;17:435-47.
Comerota AJ, Throm RC, Mathias SD, Haughton S, Mewissen M. Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life. J Vasc Surg 2000;32:130-7.
Thomas SM, Goodacre SW, Sampson FC, van Beek EJ. Diagnostic value of CT for deep vein thrombosis: Results of a systematic review and meta-analysis. Clin Radiol 2008;63:299-304.
Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev 2016;11:CD002783.
Lu Y, Chen L, Chen J, Tang T. Catheter-directed thrombolysis versus standard anticoagulation for acute lower extremity deep vein thrombosis: A meta-analysis of clinical trials. Clin Appl Thromb Hemost 2018;24:1134-43.
Mastoris I, Kokkinidis DG, Bikakis I, Archontakis-Barakakis P, Papanastasiou CA, Jonnalagadda AK, et al.
Catheter-directed thrombolysis vs. anticoagulation for the prevention and treatment of post-thrombotic syndrome in deep vein thrombosis: An updated systematic review and meta-analysis of randomized trials. Phlebology 2019;14:0268355519835618.
Thomas M, Hollingsworth A, Mofidi R. Endovascular management of acute lower limb deep vein thrombosis: A systematic review and meta-analysis. Ann Vasc Surg 2019;58:363-70.
[Table 1], [Table 2]