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% )
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
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.
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.
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.