VICTORIA trial (2) tested the efficacy of Vericiguat, a soluble guanylate cyclase (sGC) receptors activator, on top of the standard drugs in 5050 heart failure (HF) patients with reduced Ejection Fraction (HFrEF). The efficacy criteria was a composite of cardiovascular (CV) death or first HF hospitalisation. Significantly, patients were at very high risk (Mean EF: 29%, 31% with devices, 17.5% death among the placebo group) and follow-up was quite short (11 months).
The control group's event rate was 37.8%, 4.2 points higher than for patients who received vericiguat. (HR 0.90 [0.82 - 0.98]; p=0.019) This reduction was driven by a significant drop in HF hospitalisations.
These results may seem modest. They are in fact impressive, considering the severity and the short follow-up. Translated in absolute risk, this means that one should treat 24 patients for one year to avoid one event. Moreover, safety data were reassuring, with no excessive hypotensive events and no deleterious renal effects.
Considering these very encouraging results, sGC activators may become an alternative to the recent “new” HF drugs (eg SGTL2 inhibitors and natriuretic peptides). A new milestone in the field of the future guideline writers.
A number of presentations concerned the new oral anticoagulants (NOAC) use in vascular pathology.
CARAVAGGIO trial (3) tested the efficacy of oral factor X inhibitor Apixaban compared to Dalteparin, a low molecular weight heparin (LMWH) in 1,155 cancer treated patients with venous thrombo-embolism (venous peripheral thrombosis or/and pulmonary embolism) with a non-inferiority protocol.
Over 6 months of follow-up, a recurrent thromboembolism occurred in 32 Apixaban (5.6%) and in 46 Dalteparin patients (7.9%) (HR 0.63; 0.37 - 1.07). This risk difference met the criteria for non inferiority (P < .001). The risk for major bleeding, including major gastrointestinal (GI), was similar in the two groups (apixaban=3.8%; dalteparin=4%). Clinically relevant non major bleeding was however more frequent in the apixaban group (9.0% vs 6.0%), essentially in the genitourinary and the upper respiratory tracts.
In guidelines LMWH are the gold standard in cancer related venous thromboembolism (VTE) treatment, but Edoxaban, Rivaroxaban and now Apixaban, represent an additional option. However, the huge heterogeneity in the populations enrolled in these different trials, concerning particularly the type and the stage of cancer, and the absence of head to head trial, do not allow a comparison between these three drugs.
Thus, the choice of therapy should be tailored upon singular clinical data, considering that LMWH should still be preferred in particular cases (patients with primary and metastatic brain lesions, hematologic cancers, receiving newer cancer therapies, or having undergone surgery involving the upper gastrointestinal tract).
PRONOMOS trial (4) compared Rivaroxaban(10mg) to Enoxaparin (40mg) in preventing venous VTE after non major orthopedic surgery requiring immobilization for at least 2 weeks in 3,604 young patients with a moderate risk for VTE.
The primary endpoint of major VTE (a composite of deep venous thrombosis, pulmonary embolism, or VTE-related death during the treatment period) occurred in 4 patients on rivaroxaban (0.2%), and 18 patients on enoxaparin(1.1%) (HR 0.25; 0.09 - 0.75; p < .001 for noninferiority, p = .01 for superiority). The incidence of bleeding did not differ between the groups and was low, around 1%, with major bleeding in 0.6% and 0.7% of rivaroxaban and enoxaparin patients, respectively.
Finally, Rivaroxaban 10mg, started 6 to 10 hours after surgery showed a net clinical benefit on Enoxaparin in VTE prophylaxis in this population and may replace LMWH, actually recommended by the European guidelines “when risk of a thrombotic event exceeds that of a bleeding event".
VOYAGER PAD trial (5) compared the “COMPASS derived” combination of twice a day rivaroxaban 2.5mg and aspirin, to once a day aspirin in 6,564 patients with symptomatic peripheral artery disease (PAD) who underwent a vascular intervention (surgery in 35%, combined procedure in 65%). The superiority of the combination on aspirin alone (HR 0.85 [0.76-0.96]; P=0.0085) was essentially driven by an impressive decrease of acute limb ischemia observed during the three years follow-up. More TIMI major bleedings were seen in the combination group than in the aspirin alone (2.7% vs 1.9% ; HR 1.43 [0.97-2.10] p=0.0695) but the clinical benefit was in favor of the combination strategy: treating 50 patients for one year avoids one event with a bleeding risk of 0.2%. Important To note, adding clopidogrel to this two drug combination (50% patients in the combination group were in this case) produced no added efficacy but caused additional bleeding episodes… This association should either be avoided or be used very briefly after a peripheral stent or surgery.
TAVI procedures were of course largely present in the topics.
POPULAR TAVI, an open label randomized trial (6) compared two anticoagulation strategies in TAVI patients with atrial fibrillation (AF): 157 of them received oral anticoagulation (OAC) alone, clopidogrel 75mg was associated in the other randomized group of 156 for 3 months after the procedure. VKA were used in 75% of the population and NOACS in 25%.
Despite some limitations due to the trial design, the study emphasises the importance of VARC-2 criteria bleedings observed at one year: 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (RR 0.63; [0.43 - 0.90] p = .011). No difference was noted in the ischemic events occurrence, but the small size of the population does not allow any conclusion. Nevertheless, the trial suggests that, in TAVI patients with an indication for long term anticoagulation, it is safe to give only an OAC (warfarin or NOAC), and not add clopidogrel.
This is a rapid and of course incomplete selection of communications likely to modify our daily practice.
The decision taken by the ACC administration facing the current situation shows anyway that a solution is always possible, even in the most critical conditions. Let’s hope this confining will be as efficient and as brief as possible, and that we all may soon meet again and not just on our video screens.