Note: A hodgepodge of trials, added to as I come across them at work, during teaching or whilst preparing pages for this site. Interpretation of trial results is opinion (my own or my teachers’) and is included only as a prompt to read further and not as gospel.

VTE

Long Term Risks of Recurrent VTE, BMJ 2019

Meta-analysis, >7500 patients with Unprovoked or Minimally Provoked first VTE who received a minimum of three months treatment before stopping anticoagulation.

Cumulative incidence of recurrent VTE (time after discontinuing AC):

  • 10% at 1 year

  • 16% at 2 years

  • 25% at 5 years

  • 36% at 10 years

Cumulative incidence of fatal recurrent PE:

  • 0.7% at 2 years

  • 1% at 5 years

  • 1.5% at 10 years

Pooled fatality rate if recurrent VTE occurs = 3.8%

Sex: Men 1.4x rate of recurrence compared to women

Site: Distal DVT less likely to recur than other sites

(Not from this study but bear in mind that annual risk of major bleeding on AC = 1.2%. Converts to a risk of 1.3% at 10 years, compared to the fatal recurrent VTE of 1.5% )

HOKUSAI VTE 2018

Open label, non-inferiority study of edoxaban vs dalteparin

1050 patients

Edoxaban 60mg OD (30mg if CrCl 30-50, body weight <60kg or taking P-glycoprotein inhib)

Dalteparin 200 U/Kg for 30 days, thereafter 150 U/Kg. Dose reduced if plt count <100!

 

Primary outcome = composite of recurrent VTE or major bleeding = Edox 12.8%, Dal 13.5%

 

Edoxaban = 7.9% recurrent VTE, 6.9% major bleeding

Dalteparin = 11.3% recurrent VTE, 4.0% dalteparin

Site of 1st VTE Predicting Site of Recurrence, JTH 2010

Meta-analysis, >2500 patients with a first symptomatic VTE who were followed after AC was stopped.

5-year cumulative rate of PE or DVT recurrence = 22.6%

If PE first, 5-year cumulative rate of recurrence as PE or DVT 22%, and for PE 10.6%

If proximal DVT first, 5-year cumulative rate of recurrence as PE or DVT 26.4%, and for PE 3.6%

If distal DVT first, 5-year cumulative rate of recurrence as PE or DVT 7.6%, and for PE 1.2%

i.e. the risk of recurrence as PE was 3.1 fold greater in patients with a first PE compared to a first proximal DVT.

& first proximal DVT 4.8 fold higher cumulative recurrence rate than distal DVT.

ttp

TITAN 2016, Phase II

30 days capla for TTP diagnosed based on clinical basis (ie pre-ADAMTS13 level result)

Could not recruit, stopped early, ?Poor study design (Drug have to be given before PLEX)

Despite this, did show reduced time to platelet recovery, reduced exacerbation, but higher relapse

Conclusion: Bridging therapy that reduces microthrombi but does not treat the underlying disease

 

HERCULES 2019, Phase III

Randomised, double-blind, placebo-controlled, multi-national study

Plasma exchange allowed prior to starting drug

Able to extend drug beyond 30 days if ADAMTS13 level still low, or if exacerbation occurs.

Reduces No. of exchanges, volume of plasma, No. of ICU days, No. of days in hospital

SE: More bleeding, but minor sites and severity (nose, gums) – theory: organs don’t bleed as full of microthrombi, skin and epithelium has the space to bleed. Aim to manage symptoms, but do not stop caplacizumab.

IVC Filters



PREPIC-1 NEJM 1998

400 patients. Permanent IVC filter to prevent PE in patients with a proximal DVT

Primary end point: New radiological PE at 12 days. 1.1% filter vs 4.8% no filter.

BUT not statis. significant, study under recruited/under powered (original target 800), missing data

2-yr follow-up: Increased risk of DVT recurrence in filter group (20.8% vs 11.6% if no filter)

No effect of immediate or long-term mortality.

PREPIC-2 JAMA 2015

Retrievable IVC filter, effect on risk of recurrent PE in patients who also receive anticoagulation

Primary end point: Symptomatic recurrent PE at 3 months (3% vs 1.5%, not statistically significant)

Note also substantial number of filters could not be retrieved

Conclusion: Retrievable IVC filters do not reduce risk of symptomatic recurrent PE in anticoagulated patients.

JAMA Netw Open 2018

Association between IVC filters for VTE and 30-day mortality rates, in patients who did not receive anticoag.

US insurance registry study, 126,000 patients. Not randomised, Availability bias, Immortal time bias.

Noting study limitations, results suggest increase 30-day mortality associated with use of IVC filters.