Day Two
Dr Nadir Elamin, Cardiology SpR
This was an excellent day which saw the presentation of some key trials that will affect practice such as POPULAR TAVI, PARALLAX AND DAPA-CKD.
ISAR-PLASTER
In the coronary interventional field, Steffen Massberg presented the results of the ISAR-PLASTER study assessing the safety and efficacy of a novel antagonist to Platelet GPVI in elective percutaneous coronary intervention (PCI). The novel GPVI inhibitor Revacept binds to the exposed collagen to slow platelet aggregation. The trial objective was to test the efficacy and safety of Revacept in patients with chronic coronary syndrome undergoing percutaneous coronary intervention and receiving standard dual antiplatelet therapy (Aspirin + Clopidogrel).
In this multicentre, randomised, double-blinded study, 334 patients with chronic stable coronary artery disease with an indication for PCI were randomised to either Revacept 160mg (n=120), Revacept 80mg (n=121), or placebo (n=93). The primary endpoint was death or myocardial injury defined as an increase in high sensitivity troponin (hsTnT) value more than five times the upper limit of normal at 48 hours. The secondary endpoint included all-cause mortality at 30 days and Bleeding BARC type 2 or more at 30 days. Additionally, the analysis of platelet function at 48 hours was carried on for all patients.
Revacept induced a very strong platelet inhibition compared to placebo (p=0.018). There was no significant difference in death or myocardial injury (p=0.0975) as well as in peak hsTnT at 48 hours (p=0.443). Although Revacept was found to reduce the platelet function significantly, there was no significant difference in bleeding risk (p=0.362).
Revacept showed its safety in patients with low ischaemic risk chronic coronary artery disease with a significant reduction of platelet function without affecting the risk of bleed.
As a novel therapeutic strategy, GPVI inhibitors such as Revacept should be explored in patients with high ischaemic risk.
Looking forward to the next 2 days.
Dr Stephanie Connaire, Cardiology SpR
Heart Failure
One of the most anticipated presentations of the day was on the PARALLAX trial which looked at sacubitril/valsartan versus individualised RAAS blockade in patients with HFpEF and HFmrEF (LV >40%).
Key points:
- PARALLAX demonstrated a significant reduction in NT-proBNP with sacubitril/valsartan compared to individualised medical therapy (IMT).
- Sacubitril/valsartan had no additional benefit on the 6 minute walk test.
- The KCCQ quality of life score improved in both treatment groups, with an early benefit at 4 weeks of sacubitril/valsartan that was no longer significant after 24 weeks.
- Sacubitril/valsartan reduced HF hospitalisations and slowed the decline in renal function compared with IMT
- These results are consistent with the findings from PARAGON-HF and provide further evidence for the potential benefits of sacubitril/valsartan in patients with HFmrEF or HFpEF.
Professor Theresa McDonagh discussed the available evidence for the treatment of HFmrEF. There has been no specific trial of HFmrEF, however, some conclusions can be made from existing key heart failure trials including:
- CHARM
- TOP-CAT
- PARAGON-HF
- SENIORS
- DIG trial
Overall, the existing trial data suggests that HFrEF treatments are useful in HFmREF and the phenotype of HFmrEF is closer to that of HFrEF than HFpEF.
Later in the evening we heard a number of presentations on iron deficiency in heart failure. Iron deficiency in patients with chronic heart failure is common and it is an important comorbidity irrespective of the presence of anaemia. Both the FAIR-HF trial and the CONFIRM-HF trial showed that quality of life and exercise capacity was improved by intravenous iron replacement. The 2016 ESC heart failure guidelines recommend that all patients with heart failure are screened for iron deficiency with serum ferritin and transferrin saturation and the cut-off values for iron deficiency are based on the FAIR-HF and CONFIRM-HF studies.
The IRONOUT-HF study tested the effect of oral iron versus placebo on exercise capacity and showed that there was no improvement in peak exercise oxygen consumption and iron levels did not improve after oral iron. Therefore ESC 2016 guidelines recommend the use of IV ferric carboxymaltose to treat iron deficiency in HFrEF.
Professor Piotr Ponikowisk highlighted that there is not yet any trial data to show whether IV iron actually improves hospitalisation or mortality. There are three current ongoing large RCTs which are all looking at the primary endpoints of hospital admissions for heart failure and cardiovascular death.
- FAIR-HF2
- HEART-FID
- IRONMAN
Additionally, the AFFIRM-AHF trial has studied patients with acute heart failure and whether IV iron reduced hospitalisations and mortality. The results of this should be available later this year.
Looking forward to the next 2 days.
Dr Rajiv Sankaranarayanan, Consultant Heart Failure Cardiologist
Day 2 of the ESC Congress was dominated by results and discussions emanating from the PARALLAX Trial
PARALLAX RCT compared the effects of individual RAASi versus ARNI on NT‐proBNP levels, exercise capacity, quality of life, and symptom burden in HF patients with EF >40
🔹SacubitrilValsartan vs Val / Enal / placebo
🔹LVEF>40% (amended from >45%), NYHA2-4
🔹Excluded acute #HF, hypotension
Two primary outcomes:
- Significant reduction seen in NTproBNP at 12wks
- No change in functional capacity with 6 minute walk distance at 24wks
Secondary outcome measures:
- No significant change in symptom status based on KCCQ or NYHA Class
Based on this trial results, it is unlikely that ARNIs can be considered efficacious in HFpEF/HFmREF at the moment.
A meta-analysis of the 2 SGLT-2 trials was presented at the ESC Congress (Zannad et al. Lancet) showed that the 2 drugs have a consistent reduction (test of heterogeneity not significant) in all cause death & heart failure hospitalization irrespective of diabetes status. They also improve renal outcomes in patients with HFrEF.
Commentary Opinion: It is important that the wide ranging benefits of SGLT2I seen in HFrEF patients irrespective of diabetic status based on several RCTs, is translated into national and international guidelines soon.
Looking forward to the next 2 days.
