ST CATHERINE’S HOSPICE Primary thromboprophylaxis in advanced disease MJ Johnson

(The Mail on Sunday, 17/12/2000) 2

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(The Sunday Telegraph, 28/1/2001) 4

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Daily Mail 3/2/01 6

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Background VTE : important cause of death in cancer patients Potentially preventable with appropriate risk assessment and prophylaxis Therefore a healthcare priority for many countries Some (e.g. UK) using financial incentives and targets to drive implementation International guidelines: Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 2013 Jan;11(1):56-70.

What about palliative care? Clinical relevance and research focus very recent in palliative care Moderate to high risk of VTE – Advanced/active disease – Received ++ therapies (chemo/surgery) – Poorly mobile Secondary prevention is much more accepted Still divided opinion about primary prevention – Agreement not for those imminently dying But – hospice care now not just for the imminently dying

Things have changed Hospice is no longer “the Death House” But – Only 7% SPC units have TP guidelines (Noble 2007) – Not perceived as “a big problem” by clinicians – Outcome measures in studies not appropriate – Studies don’t include our patients – “A big PE is a nice way to go” (Noble 2008) However, difficult to keep being an ostrich… 10

11 Why prevent VTE in palliative care patients? High risk – Up to 50% in hospice in patients VTE confers a poor prognosis Cause symptoms – Attributable and non attributable Challenging to treat – Bleeding – Recurrent thrombosis – Six months of LMWH (Noble et al Lancet Oncology 2008)

Current state of play 12 Majority of palliative care patients admitted through medical take… …will be receiving PTP by default Some admitted to the hospice…… ….won’t get PTP when they could benefit

Hospice VTE risk assessment project The utility of risk assessment tools in patients with advanced disease, and prediction of symptomatic VTE is unknown. Investigation: i)what is the relationship between risk of VTE and development of symptoms and, ii)what is the utility of risk assessment tools for these patients?

Method Retrospective consecutive admission case-note data from seven UK hospices Data collected during an evaluation of a VTE risk assessment protocol – Pan Birmingham Cancer Network palliative-modified Thromboembolic Risk Factors (THRIFT) Consensus Group criteria, – presence/absence of a temporary elevated risk (TER) of VTE. Symptoms/signs during admission consistent with possible VTE were documented.

Analysis plan An exploration of the association of THRIFT, TER with – prescription of PTP, – development of symptoms An estimation of the utility of THRIFT and TER in predicting symptomatic VTE during their hospice admission: – sensitivity, specificity, – predictive value (PPV and NPV), – likelihood ratios (LR(+/-)) – odds ratios Tests were 2-sided using a significance level of 5%, odds ratios and accuracy measures such as sensitivity are presented with 95% confidence intervals.

results Total population: N= (4%) prescription of PTP on admission; (68 came on PTP; 13 of these continued; 32 new prescription) “Clinically relevant population” : N = 528 (45%) – The population who would have been eligible to have PTP with LMWH – Excludes Contraindication to anticoagulation (bleeding, dying, thrombocytopenic) N= 496 Already on therapeutic anticoagulation N = 139

Patient characteristicsTotal population Age, years70.1 (SD 13.1); range 23 to 99 Sex, male627 (54%) Diagnostic category Cancer949 (82%) THRIFT Risk Score Low48 (4) Moderate968 (83) High148 (13) TER Risk Score Yes880 (76%) No279 (24%) missing5 (0%)

Symptoms (N=528) Clinically Relevant Population Total Population N=528 (%)N=1164 (%) Symptom Pleuritic chest pain12 (2)21 (2) Leg swelling14 (3)32 (3) Breathlessness 47 (9)99 (9) Overall 12% in clinically relevant group Those not prescribed PTP had OR 1.74, 95% CI 0.69 to 4.4, p=0.241 Too few with PTP for estimation

Symptoms by risk THRIFTTER symptoms N (%) HighModerateLowYesNo Total Yes4 (10)57 (12)1 (4)26 (21)36 (9)62 (12) No36 (90)403 (88)27 (96)98 (79)368 (91)466 (88) Total40 (100)460 (100)28 (100)124 (100)404 (100)528 (100) 21% of those with a TER developed symptoms compared to 9% of patients without a TER (Chi- squared, p<0.001).

Prediction of symptomatic VTE VTE risk assessmentClinically important population N=528; (95% CI) THRIFT 1; High+Mod v Low Sensitivity (%)98.4 (91.3, 100.0) Specificity (%)5.8 (3.9, 8.3) THRIFT 2; High v Mod+Low Sensitivity (%)6.5 (1.8, 15.7) Specificity (%)92.3 (89.5, 94.5) TER Sensitivity (%)41.9 (29.5, 55.2) Specificity (%)79.0 (75.0, 82.6)

Limitations Symptoms not routinely investigated with imaging - proxy measure Number caused by confirmed VTE events not known Severity not systematically documented –But significant enough to the patient and doctor to document in the clinical record. Retrospective chart review –symptoms were not systematically sought for, graded or documented –Therefore likely to be an underestimate.

Conclusions 1: Does risk matter? Most patients admitted to these hospices were at moderate to high risk of developing VTE during their stay. Does this matter? There is a highly significant association between TER and “proxy” symptoms in those who could have PTP

Conclusions 2: what should we do about it? Use TER rather than THRIFT for hospice patients on admission But… Unknown whether PTP improves outcome Unknown what effect symptoms have on QoL Therefore consider PTP in those at risk and discuss with patient