Brief Overview of the Trials Presented at ESC Congress 2024

Helios B

This trial showed that the RNA interference therapeutic agent Vutrisiran, which inhibits the hepatic transthyretin, given subcutaneously at a dose of 25 mg every 12 weeks for 36 months, decreased the incidence of death from any cause in patients having transthyretin amyloidosis (ATTR) with cardiomyopathy (HR 0.72, P< 0.01). The effect was seen irrespective of the use of tafamidis in the studied population. The drug prevented the worsening of the heart failure by reducing the transthyretin protein. The quality of life and functional capacity was preserved as the overall population were healthier at baseline. Of the drugs used at the start of the trial, 22% were using tafamidis and 33% were using SGLT2i. Despite this, drug use led to a decrease in death over the 42 months of the trial (HR 0.65). Most of the patients had wild-type ATTR, a smaller proportion had variant ATTR, and there were more men and white population which represented the usual pattern of the ATTR. In the previous trial (HELIOS A), the effect of this drug was found to be beneficial in patients with neuropathy. The present trial extended its impact to patients with wild or variant-type ATTR cardiomyopathy.

Fine Arts HF

This international, randomized, double-blinded trial in symptomatic heart failure (HF) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) found that the use of finerenone resulted in a lower rate of worsening HF events and cardiovascular (CV) death compared to the placebo. The median age of the 6,000 study participants was 72 years. Of the population, females were 46%. The median duration of follow-up was 32 months. The finerenone dose was 20 mg initially, which was increased to 40 mg after four weeks based on the serum potassium levels, or if the estimated glomerular filtration rate (eGFR) had not declined by more than 30%. In the baseline characteristics of the patients enrolled, the median LVEF was 53% (36% had 40%-50%). Almost half of the patients had eGFR of 20 to 60 ml/min/m². One-third of the patients had NYHA class III to IV HF, and 60% had a history of prior HF hospitalization. Nearly 85% of the patients experienced an event in the last three months before enrolment. In terms of medications for HF, only 14% of patients were using sodium-glucose cotransporter 2 inhibitors (SGLT2i), despite diabetes being present in 41% of the participants. Additionally, the use of glucagon-like peptide-1 receptor antagonists (GLP1RA) was limited to just 3%. When analyzing the primary outcomes across different categories of LVEF, the benefits of finerenone were more pronounced for patients with an LVEF > 60%. The use of SGLT2i did not affect the primary outcome; however, a higher number of events were reported in the group that used SGLT2 inhibitors.

Comments: This is the first trial to demonstrate the efficacy of a neurohumoral modifying agent in patients with preserved or mildly reduced EF. The main outcome of the trial was a reduction in the recurrence of worsening HF events rather than a decrease in CV mortality . The decrease in CV mortality was not seen because of a lower incidence of coronary artery disease (CAD), less ischemia, and fewer males in the population with elevated LVEF. Why had this drug shown benefit? – Patients with higher LVEF levels often had a history of hypertension and chronic kidney disease (CKD) – increased collagen deposition – which is counteracted by the studied drug. This trial has the potential to change guidelines of HFPEF management regarding the use of MRAs moving their recommendation from class IIb to class IIa, like the recommendations for SGLT2i. Increased events in both groups, particularly among those using SGLT2 inhibitors, may be related to a lower EF and a history of HF and CAD in those patients. The effectiveness of the treatment for CKD cannot be fully assessed due to a smaller patient population and a shorter follow-up period.

Scoff

According to this trial, fasting before procedures that require conscious sedation is not necessary . A total of 716 patients were randomized to either a fasting group or a regular meal group before elective cardiac procedures (including angiography, coronary interventions, or the implantation of cardiac devices). The median age of the enrolled patients was 69 years, and 35% of them were female. Patients in the fasting group were advised to refrain from solid foods for 6 hours and from liquids for 2 hours. The primary composite outcomes—hypotension, aspiration pneumonia, hyperglycemia, and hypoglycemia—occurred in 19.1% of patients in the fasting group compared to 12.0% in the non-fasting group. In the intention-to-treat (ITT) analysis, which included all randomized patients regardless of whether they completed the assigned protocol, the estimated mean posterior difference was -5.2%, favoring the non-fasting group. When assessed for procedure-related outcomes, there were no significant differences between the two groups regarding the incidence of contrast-induced nephropathy, the need for intensive care, or the requirement for ventilation. The patient satisfaction was higher in the non-fasting group. Previous observational studies CHOW NOW, TONIC, and Fast CIED showed similar results but were single center studies. The results of this trial, which is an investigator-initiated, open-label, blinded endpoint trial conducted at six centers in Australia, may change the traditional perspective on fasting before cardiac procedures requiring conscious sedation.

Comments: This is good news, indicating that there is no significant difference between fasting and non-fasting before the procedures. The comfort of the patient is the top priority during the procedures . However, it is important to conduct studies involving a larger and more diverse population, patients with various comorbidities that were not analyzed in the trial. This will help avoid the assumption that a one-size-fits-all approach is appropriate, as it could lead to unexpected complications.

Occupi

This trial evaluated the effect of intravascular imaging with optical coherence tomography (OCT) on clinical outcomes in patients undergoing PCI with drug-eluting stents (DES) in anatomically complex lesions. The OCT guidance led to a reduction in the risk of the primary composite outcome of cardiac death, myocardial infarction (MI), stent thrombosis (ST), or ischemia-driven target vessel revascularization (TVR) at 1 year. The reduction was mainly due to the reduction in the spontaneous MI and TVR . This trial leads us to a strategy for the use of OCT in complex PCI for better outcomes. Compared to the previous two trials of OCT, which were related to only one subset of the complex lesions (ILUMIEN IV angiographically complex lesions and patients with high clinical risk or comorbidities like diabetes, OCTOBER trial – only on bifurcation lesions) this trial is the first randomized trial evaluating the efficacy in all the complex lesions. The RENOVATE COMPLEX PCI evaluated the efficacy of both IVUS and OCT in complex lesions showing that the target vessel failure (TVF) decreased by 36% over the follow-up of 2.1 years. Unlike the RENOVATE COMPLEX PCI trial which has used OCT in only a quarter of the cases, the OCCUPI trial was an exclusive OCT trial. The ILUMIEN IV trial has shown a decrease in ST in OCT-driven PCI compared to the angiography-guided PCI despite showing an overall negative result. The OCTOBER trial showed superior efficacy on OCT guidance in bifurcation lesions. The OCCUPI differs from the above two trials in the following aspects – in the ILUMEIN IV trial, the repeat revascularizations were done less due to the COVID pandemic and the included patients were diabetic irrespective of their lesion complexity, which might have nullified the advantage of OCT. This trial did not include diabetes if there is no anatomically complex lesion. Apart from the use of two stents in bifurcation lesions (10% vs 3%), the minimal lumen diameter was 2.79 vs 2.59 compared to 2.65 vs 2.61 mm in the ILUMIEN IV trial , leading to superior outcomes in this trial. Furthermore, those patients who have satisfied the optimization criteria on OCT have fewer primary outcomes compared to the one with sub-optimization. The effect of suboptimization is to be studied in future studies as optimization cannot be done in all cases. There was no increase in risks of contrast-induced nephropathy in the patients undergoing OCT. Some limitations to be considered regarding this trial are: the representation has fewer female patients, patients are only from South Korea, underpowered study due to less occurrence of the predicted primary endpoints, unblinded OCT procedures, and experienced operators in IVI using the angiographic guidance.

Senior Rita

Routine invasive therapy for non-ST-segment elevation myocardial infarction (NSTEMI) in older patients has not shown any benefit compared to conservative therapy. A total of 1,518 patients over the age of 75 were randomized to receive either routine invasive therapy or conservative therapy for NSTEMI. The median follow-up period was four years. The median age of the participants was 82 years, and 45% were female. Of the clinical characteristics, diabetes was seen in 1/3 of the patients, 32.4% were frail, and 62.4% had cognitive impairment. Only 17.8% were classified as well without active disease, and 13.8% were deemed very fit. Most interventions utilized radial access, with revascularization performed in half of the patients studied. In the conservative therapy group, 26% were converted to angiography, and 13% underwent revascularization . The primary endpoints of CV death and MI did not differ between the two groups. The bleeding rates were higher in the invasive therapy group. The management of NSTEMI in patients aged over 75 years must be individualized, considering factors such as angina burden, lesion complexity, comorbidities, and high-risk elements in the decision-making process.

Comments: For patients aged <75 years, an invasive strategy is preferred for NSTEMI; however, this approach does not hold for patients aged > 75 years, as demonstrated in this trial. Treatment should be individualized. Moreover, rather than the mortality benefits, the quality of life is to be assessed in this population.

Rec Cage Free

Despite the advances in stent technology, DES has its disadvantages—the occurrence of stent thrombosis, metallic frame in the coronaries, and in-stent restenosis. Avoiding a stent with a drug-coated balloon (DCB) is efficacious, which was not evaluated on a larger scale. This was studied in this multicenter randomized non-inferiority trial in noncomplex coronary lesions, irrespective of the vessel diameter. Post dilation with the balloon (either semi-compliant, noncompliant or cutting balloon at the discretion of the investigator) the patients were randomized to either a paclitaxel drug-eluting balloon or a second-generation thin strut sirolimus-eluting stent in this trial done in China. Rescue DES implantation was done in the patients with unsatisfactory results on DEB . Approximately 2500+ patients were enrolled, who had a mean age of 62 years and 30.7% were females. All the participants were from China. About 10% of patients underwent rescue DES implantation in the DEB group. The primary endpoint occurred in 6.4% of patients in the DEB group compared to 3.2% in the DES group; the non-inferiority margin being an absolute difference of 2.48% was not attained. There was no difference in the periprocedural MI in both groups (0.9% vs 0.8%). In denovo coronary artery lesions, the DEB implantation was not found to be non-inferior compared to DES, which means DES should be the primary strategy in treating the lesions. It was an investigator-initiated trial and blinding was not done because of the use of DCB. However, the primary endpoint was event-driven, not subjective. The Paclitaxel-coated balloon used in the trial was not approved worldwide. Around 21% of the population did not achieve the desired predilation (not randomized) and 9.4% had a crossover to the DES, which should be kept in mind as it was an ITT analysis. The trial results do not transfer to a sirolimus-eluting balloon. The subjects were only from China and females were underrepresented. Repeated angiography might have led to increased revascularization in the DEB. The Kaplan-Meier curve separated earlier showing the efficacy of DES as early as 100 days. Further studies are needed before concluding the inferiority of DCB.

Abyss

This trial was conducted in 49 centers across France and involved patients with a history of myocardial infarction (MI) who were on beta-blocker (BB) therapy. The participants had LVEF greater than 40% and had not experienced any serious CV events in the past six months. Of the 3,700 patients studied, discontinuing beta-blocker treatment did not result in an improvement in their quality of life.

Comments: Beta-blockers have significantly evolved over the past century in the management of cardiac patients. Initially, they were contraindicated for patients with heart failure; currently, they are recommended as one of the key treatment pillars in management for these patients. Beta-blockers have cardiac mortality benefits for individuals who have experienced an MI particularly those with left ventricular dysfunction. Despite their benefits, the continued use of BB can lead to side effects such as fatigue, worsening diabetes, decreased libido, and erectile dysfunction. Recent studies, including the REDUCE MI, have raised questions about the use of beta-blockers in patients with normal LVEF. Before generalizing the findings of these trials—which indicated no significant benefit in improving quality of life—it is essential to consider various factors, such as the trial population (restricted to a single country), the duration of follow-up (1-2 years), and the specific reasons for beta-blocker use in the study participants involved here. For patients who had a myocardial infarction and show improved LVEF with no other indications for use of beta-blockers, and who are experiencing side effects, discontinuation of the medication may be a viable option. However, additional studies are needed to provide a stronger recommendation.

Epic Cad

Edoxaban monotherapy in patients with atrial fibrillation and coronary artery disease led to fewer events than dual therapy. Patients with atrial fibrillation and coronary artery disease using oral anticoagulant and antiplatelet therapy are at increased risk of bleeding. This trial done in South Korea consisting of patients with a mean age of 72 years and 30% females has shown fewer events with edoxaban monotherapy compared to dual therapy in patients with chronic coronary syndrome and atrial fibrillation. The mean CHADVaSc score of the enrolled population was 4.3. The primary endpoint occurred in 6.8% of the monotherapy group and 16.2% of patients receiving dual antithrombotic therapy. Similarly, the bleeding events were less in the monotherapy compared to the dual therapy (HR 0.34). However, larger population trials and patients of non-Asian origin are to be included with a longer duration of follow-up before considering the change in the guidelines in this subset.

Reshafe HF2

This trial demonstrated that Mitral TEER was beneficial for heart failure patients with significant mitral regurgitation, compared to GDMT alone. This open-label study enrolled 505 patients with symptomatic HF and severe MR who were on guideline-directed medical therapy (GDMT). Participants were assigned to receive either Mitraclip (M TEER) or continue with GDMT. The median follow-up period was 24 months, and the patients had a median age of 70 years, with 20% being female. The LVEF of the patients ranged from 20% to 50%. A history of MI was present in 55% of the patients, while 48% had a history of percutaneous coronary intervention (PCI) and 26% had undergone coronary artery bypass grafting (CABG). Ischemic heart failure was the etiology in 65% of the cases. The median EF was 32%, and 65% of patients had a history of hospitalization due to heart failure. Overall, moderate mitral regurgitation was observed in the study group . After the Mitraclip procedure, mild mitral regurgitation was noted in 7.9% of patients. In the Mitra clip group, there was a 36% reduction in hospitalizations due to HF at one year, with a number needed to treat (NNT) 5.1 to prevent one event. The most significant benefits were seen in the reduction of HF hospitalizations and improved quality of life, particularly among those who had been hospitalized in the previous year.

Comments: This trial confirmed the findings of the COAPT trial but resembled the MITRA FR trial features, which was a negative trial concerning the use of Mitraclip in patients with mitral regurgitation. This trial demonstrated positive results compared to MITRA FR in patients with moderate mitral regurgitation. The guidelines should be updated regarding the use of Mitra Clip in symptomatic heart failure patients having significant mitral regurgitation.

Popular Pause

Approximately 1/3 of the patients undergoing TAVI have an indication for use of oral anticoagulant because of the concomitant diseases. Continuation of the drugs leads to bleeding, and stopping the drug will lead to thromboembolism. This trial evaluated the comparison of continuation of the oral anticoagulants vs interruption before TAVI. It has evaluated the safety but not the efficacy of the continuation of the anticoagulant therapy peri procedurally . The trial showed noninferiority of the continuation of the therapy compared to the interruption of the anticoagulant, unlike the previous trials which were shown to be superior in reducing the events. It is an open-label study, the occurrence of neurological events was evaluated clinically and it is an underpowered study.

Sham PVI

This trial demonstrates that, in patients with paroxysmal or persistent atrial fibrillation (AF), cryo-balloon pulmonary vein isolation (PVI) was associated with a reduced burden of AF and significant symptomatic improvement compared to a sham procedure . This double-blinded randomized trial enrolled 126 patients, with AF burden assessed via an implantable loop recorder (ILR) that tracked AF episodes lasting longer than two minutes. Those with longstanding AF lasting over a year, other arrhythmias requiring ablation, a left atrial (LA) diameter greater than 5.5 cm, an LVEF of less than 35%, or a history of prior AF ablation were excluded from the study. Patients were followed for six months. The median age of the population was 67 years, and 29% were female. Persistent AF was observed in 79% of patients, and among those on AADs; beta-blockers were used by 89% and amiodarone by 24%. The average CHA2DS2-VASc score was 2.0. The median time from diagnosis to the procedure was nearly two years. The procedure duration was 63 minutes, compared to 60 minutes for sham phrenic nerve pacing. The primary outcome at six months showed an AF burden of 18.2% for the cryoballoon procedure versus 43.2% for the sham procedure. Quality of life improved significantly with the cryoballoon procedure . Direct current cardioversion during the three-month blanking period occurred in 39% of the cryoballoon group compared to 48% in the sham group. The reuse of AADs after three months decreased significantly (32.3% for the cryoballoon group versus 54.1% for the sham group, P <0.001). Despite previous trials demonstrating the efficacy of cryoballoon ablation, this study—SHAM PVI is the first to show its superiority . The use of an implantable loop recorder (ILR) provided objective evidence of AF, and no crossover occurred during the study. The efficacy of ablation procedures (Cryo, radiofrequency, or pulsed-field ablation) is comparable, making these results generalizable. However, these findings may not apply to patients with prior failed ablation, longstanding permanent AF, or significant left atrial dilation.

Comments: Atrial fibrillation is associated with a range of adverse events, with the risk of embolism being particularly concerning. Several factors influence treatment outcomes, including the pill burden and side effects of AADs, patient compliance, age, and dependency. Early detection of AF and assessing the feasibility of ablation are crucial. An ablative procedure can be an effective option for managing AF and reducing the need for AADs providing significant benefits to the patients. This trial showed the efficacy of ablation; however, further research is needed to evaluate its effectiveness in a larger population and various subsets of patients.

Tight K

The role of potassium supplementation in reducing the occurrence of atrial fibrillation post-cardiac surgery was evaluated in this trial. Potassium supplementation when below 3.6meq/l vs when below 4.5meq/l does it make any difference in the occurrence of AFACS was also evaluated in this trial. Supplementing potassium to maintain levels above 4.5meq/l is a common strategy to prevent atrial fibrillation post-surgery however, it is not evidence-based, carries risks, and is costly. Of the total 1690 patients enrolled, the mean age was 65 years and the females were 15%. The primary endpoint of occurrence of atrial arrhythmia post-surgery was seen in 26.2% vs 27.8% of patients with a risk difference of 1.7%. There were no increased adverse events in the low threshold group.

Assure Des

Continuing aspirin monotherapy in patients with drug-eluting stents (DES) did not significantly reduce ischemic events for those undergoing low to intermediate-risk non-cardiac surgery when compared to a group that temporarily stopped all antiplatelet medications. This trial, conducted in South Korea, involved 926 patients who had received a DES implantation one year prior. The participants were randomly assigned to either continue taking aspirin or to stop all antiplatelet medications five days before surgery completely. The study assessed events that occurred five days before and 30 days after surgery to evaluate the efficacy of aspirin in reducing ischemic events. Surprisingly, overall events in the study were less than predicted, making it underpowered . These low event rates demonstrate the safety profile of the DES used in the study. The bleeding rates were higher in the aspirin group.

Comments: Managing patients with DES who are undergoing noncardiac surgery presents significant challenges. It is important to assess and balance the risk of ischemic events against the risk of bleeding during the surgery. The ASSURE DES study is of importance in this patient subset, and it is surprising to note that the use of aspirin did not lead to a decrease in ischemic events. Several factors should be considered before generalizing the study’s findings: it was a single-nation study, minor surgeries were performed, the specific population with DES studied was limited, and the event rate was low . High-quality data is necessary to consider changes to the current guidelines in this area.

Stop or Not

This trial demonstrated that the use of renin-angiotensin system inhibitors (RASI), whether continued or discontinued before surgery, did not significantly affect major postoperative outcomes. This open-label trial involved 44 centers in France and randomized patients with a history of using RASIs for more than three months, who were undergoing major non-cardiac surgery. Patients were assigned to either continue their medication to the day of surgery or stop it 48 hours prior. In both groups, RASIs were reinitiated orally whenever possible after the procedure. Of the 2,222 patients randomized, 65% were male, and the median age was 67 years. 98% had hypertension, 9% had chronic kidney disease, while diabetes and heart failure were present in 8% and 4% of patients, respectively. At baseline, 46% of patients were using angiotensin-converting enzyme inhibitors (ACEIs), while 54% were using angiotensin receptor blockers (ARBs). The rates of all-cause mortality and postoperative complications were similar in both groups. Hypotension episodes were observed in 41% of the discontinuation group and 54% of the continuation group . The median duration of hypotension, defined as a mean arterial pressure (MAP) below 60 mm Hg, was greater in the continuation group, with 9 minutes (range, 5-16 minutes) compared to 6 minutes (range, 4-12 minutes) in the discontinuation group.

Comments: Managing patients with comorbidities who are undergoing major non-cardiac surgery is a challenging task. Continuing the use of RASI during surgery puts patients at risk for hypotension, while discontinuing these medications can elevate the risk of hypertension and heart failure. This trial addressed this important issue. Despite 98% of patients having hypertension, the discontinuation of RASI did not result in the occurrence of hypertension, heart failure, or arrhythmias. The decision now rests with the treating doctors to stop the medications in patients at high risk of hypotension during the procedure, considering the trial results.

Quadro

Patients with resistant hypertension (RH) must be on multiple medications to control their blood pressure (BP). However, with increasing pill burden, there will be increased non-adherence to the drugs prescribed. Previously, a single pill combination with an antihypertensive, statin, and aspirin (polypill) was evaluated in primary prevention. Along those lines, a single pill containing 4 drugs (quadruple combination) was evaluated in this trial of patients with resistant hypertension. This SPC controlled the BP more effectively compared to the drugs in three separate pills. This pill contained bisoprolol, amlodipine, indapamide, and perindopril . The patients with RH underwent a run-in period for eight weeks, containing three drugs in combinations of 10/2.5/5mg or 10/2.5/10mg if tolerated. After eight weeks if the BP was >140mm Hg they were randomized in 1:1 ratio to quadruple therapy vs three drugs containing bisoprolol in 5 mg and 10mg . The primary endpoint was a change in office systolic blood pressure (OSBP). The secondary endpoint was a change in 24 ambulatory blood pressure (24ABPM) and a change in office diastolic blood pressure (ODBP), and home BP control. After eight weeks, mean OSBP reduced by 20mm Hg in the quadruple-drug group compared to the three-drug group. The secondary endpoints also favored the use of SPC. Importantly, normalisation of BP was achieved in 66.3% of patients taking the SPC. Home BP was normalized in 60% of the population. This trial showed the efficacy of the combination of four drugs with adequate control of BP in resistant hypertension.

GMRX2

Three-in-one pill therapy for effective control of hypertension was evaluated in this trial. In patients with mild to moderate hypertension, a three-drug combination pill in both doses consisting of telmisartan, amlodipine, and indapamide (10/2.5/0.625) and (20/5/1.25) were tolerant and led to better control in hypertension, compared to the placebo. The present trial compared the efficacy of the drug combination with 20/5/1.25 in patients with SBP between 140-179 and diastolic blood pressure of 100-110mm Hg and was found to be efficacious compared to the dual drug combination. The control in BP below 140/90 mm Hg was attained in 74% of patients with the SPC compared to 50-61% in dual drug combinations. The occurrence of adverse events leading to stoppage of the drug was seen in 2% of patients compared to 1% in the dual drug combination group.