Medical Cardiovascular Channel December 18, 2021
Inventory of the Top 10 Major Cardiovascular Studies in 2021!
In the upcoming year of 2021, the cardiovascular field has successively released and published multiple heavyweight studies. On December 18th, at the "Academician Lecture" of the China Cardiovascular Health Conference (CCHC), Academician Ge Junbo from Zhongshan Hospital affiliated with Fudan University reviewed and summarized important research published in the field of cardiovascular treatment in 2021 from five aspects: heart failure drug therapy, coronary artery disease treatment, left atrial appendage occlusion, antithrombotic therapy after transcatheter aortic valve replacement (TAVR), and hypertension.
Figure 1: Academician Ge Junbo
EMPEROR Preserved study: providing timely assistance for the treatment of HFpEF
Compared to heart failure with reduced ejection fraction (HFrEF), the treatment of heart failure with preserved ejection fraction (HFpEF) has always lacked effective treatment methods. The EMPEROR Preserved study published by the European Society of Cardiology (ESC) in 2021 has for the first time confirmed the efficacy and safety of the SGL2 inhibitor empagliflozin in patients with HFpEF.
A total of 5988 heart failure patients with NYHA grades II-IV and LVEF>40% were enrolled in 622 centers in 23 countries and regions. They were randomly divided into two groups and received either empagliflozin or placebo treatment on the basis of standard treatment. The primary endpoint is a composite endpoint consisting of cardiovascular death or hospitalization for heart failure.
At a median follow-up of 26.2 months, the incidence of the primary endpoint event of empagliflozin decreased by 21%, and the improvement in the primary endpoint was mainly due to a significant 27% reduction in hospitalization risk for heart failure. In addition, the decline rate of renal function in the empagliflozin group was also slower. Engeletrexed became the first drug to treat full stage heart failure. Meanwhile, we also look forward to the ongoing DELIVER study to see if dapagliflozin can replicate the effects achieved by empagliflozin in the treatment of HFpEF with LVE ≥ 40%.
Figure 2: EMPEROR Preserved research results
GALACTIC-HF study: Adding icing on the cake for HFrEF treatment
In recent years, drug therapy targets for HFrEF have become increasingly diverse. Previous studies have shown that positive inotropic drugs can improve hemodynamics, but cannot improve the clinical prognosis of HFrEF. The GALACTIC-HF study is one of the largest Phase III global cardiovascular outcome studies conducted in the field of heart failure treatment to date, and it is the first to confirm that drugs that increase myocardial contractility can improve the clinical prognosis of HFrEF patients.
The study included 8256 symptomatic chronic heart failure patients with left ventricular ejection fraction (LVEF) ≤ 35%, who were treated with OmecamtivMecarbil (OM) or placebo in addition to standard heart failure therapy. At a median follow-up of 21.8 months, the risk of heart failure or cardiovascular death was significantly reduced in the OM group, and there was no significant benefit of OM in reducing cardiovascular death.
Subgroup analysis showed that baseline LVEF was less than 28%, and the improvement in the primary endpoint event was more significant in the OM group, with a 16% decrease compared to placebo. This suggests that OM has a more significant effect on patients with lower LVEF.
Figure 3: Main Results of GALACTIC-HF Study
FAME 3 study: Three vessel lesions, FFR guided PCI vs. CABG
For patients with combined left main and/or triple vessel lesions and high SYNTAX scores, current European and American guidelines recommend coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). So, in patients with three lesions, will the treatment strategy of coronary flow reserve (FFR) combined with second-generation drug-eluting stents (DES) for PCI be superior/not inferior to CABG? The FAME 3 study explored this.
The study randomly assigned 1500 patients from 48 centers to receive FFR guided PCI or CABG treatment in a 1:1 ratio. During a 1-year follow-up, it was found that there was no significant difference in other endpoint events (such as death, myocardial infarction, stroke) between FFR guided PCI treatment and CABG group, except for revascularization.
In the FAME 3 study, the incidence of events was lower in both the FFR guided PCI group (10.6%) and the CABG group (6.9%) compared to the previous SYNTAX study's CABG group (12.4%). For patients with three vessel lesions with low SYNTAX scores, PCI treatment can be preferred; For patients with triple vessel disease with high SYNTAX scores, CABG may still be the preferred option.
Figure 4: Main Results of FAME 3 Study
FAVOR III China study: QFR guided PCI improves prognosis
Professor Xu Bo from Fuwai Hospital, Chinese Academy of Medical Sciences, gave a positive answer to the question of whether quantitative flow fraction (QFR) guided PCI can improve clinical prognosis in the FAVOR III China study presented at the Transcatheter Cardiovascular Therapy Symposium (TCT) 2021 in the United States.
The study involved 26 centers nationwide, and participants were randomly assigned to the QFR guidance group and the angiography guidance group in a 1:1 ratio. In the QFR guidance group, only lesions with QFR ≤ 0.80 are intervened. If all measured blood vessels have QFR>0.80, only drug therapy is used; The imaging guidance group followed standard imaging guidance methods and intervened based on the surgeon's visual assessment.
The results showed that compared with contrast guided PCI, QFR guided PCI had a relative risk reduction of 35% in the occurrence of major cardiovascular adverse events (MACE) within one year, mainly due to the lower incidence of myocardial infarction and ischemia driven revascularization in the QFR guided group.
Figure 5: Main Results of FAVOR III China Study
MASTER-DAPT study: DAPT duration after PCI in high-risk bleeding population
With the continuous development of DES, the incidence of stent thrombosis events has gradually decreased, bringing hope for shortening the duration of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR). So, what is the optimal DAPT duration for HBR patients after DES implantation?
The MASTER-DAPT study randomly divided 4434 eligible patients into a short-term DAPT treatment group (1 month) or a standard DAPT treatment group (3 or 6 months) in a 1:1 ratio. The two groups were comparable in terms of net clinical adverse events and major cardiovascular and cerebrovascular adverse events. In terms of major bleeding or clinically relevant non major bleeding, the short-term DAPT treatment group was significantly lower than the standard DAPT treatment group (6.5% vs. 9.4%).
The current guidelines provide an evidence level of C (expert opinion) for shortening the DAPT time of HBR patients. Future guidelines may refer to the results of the MASTER DAPT trial to increase the evidence level and shorten the DAPT time of HBR patients from 3-6 months to 1 month.
Figure 6: MASTER-DAPT Study - Net Clinical Adverse Events
LAAOS III: New Evidence for Surgical LAAO Prevention of Atrial Fibrillation Stroke
Randomized controlled trials (RCTs) such as PROTECT-AF and PREVAIL have confirmed the effectiveness of left atrial appendage occlusion in preventing atrial fibrillation stroke; However, there is a lack of evidence for left atrial appendage occlusion (LAAO) in surgery, and guidelines recommend a lower level. The LAAOS III study aims to evaluate whether performing LAAO concurrently with other cardiac surgeries can reduce the risk of stroke and systemic embolism in patients with atrial fibrillation.
A total of 4811 high-risk patients with atrial fibrillation and stroke who underwent cardiac surgery for other indications were enrolled in the study, with an average follow-up of 3.8 years. Compared with non occluded patients, patients who underwent LAAO during the same period of surgery had a significantly lower risk of ischemic stroke and systemic embolism events. There was no significant difference in the incidence of perioperative bleeding, heart failure, and death between the two groups of patients.
However, can LAAO replace oral anticoagulants; Further exploration is needed on the value of concurrent LAAO for low-risk patients.
Figure 7: Main Results of LAAOS III Study
Amulet IDE：Amulet vs. WatchmanHead to head comparison
The left atrial appendage occlusion instruments available in clinical practice mainly include plug and cover types. The Amulet IDE study is the first head to head comparison of randomized controlled trials (RCTs) between Amulet and Watchman, the two most commonly used left atrial appendage occluders. The study included 1878 stroke high-risk non valvular atrial fibrillation (NVAF) patients from 150 centers worldwide, who were randomly assigned 1:1 to either the Amulet or Watchman occluder group.
The results showed that the Amulet occluder group had a higher device based left atrial appendage closure rate (98.9%) than the Watchman occluder (96.8%), and was not inferior to the Watchman occluder in terms of primary safety and efficacy endpoints. The research department further confirmed the role of left atrial appendage occlusion in the prevention of NVAF stroke, but the anti thrombotic strategy after left atrial appendage occlusion surgery is worth considering.
Figure 8: Amulet IDE research results
ATLANTIS：Application of NOACs in TAVR postoperative antithrombotic therapy
The optimal antithrombotic regimen after TAVR surgery is not yet clear. The ATLANTIS study is another heavyweight research on the road to finding the best antithrombotic treatment plan after TAVR surgery in recent years. The study included 1510 patients who successfully underwent TAVR in 49 centers across 4 European countries. Based on indications for oral anticoagulation therapy, they were divided into two groups: the anticoagulation therapy indication group (including warfarin treatment group and apixaban treatment group) and the non anticoagulation therapy indication group (including antiplatelet therapy group and apixaban treatment group).
The results showed that regardless of whether valve thrombosis was included as the endpoint event, apixaban treatment did not demonstrate superior efficacy compared to the current standard treatment regimen (regardless of anticoagulant or antiplatelet population). Therefore, the exploration of the optimal antithrombotic treatment plan after TAVR surgery will continue.
Figure 9: ATLANTIS research results
ENVISAGE-TAVI AF：Providing important evidence for anticoagulant therapy in TAVR atrial fibrillation patients
The ENVISAGE-TAVI AF trial aims to investigate the efficacy and safety of comparison between idoxaban and vitamin K antagonist (VKA) in patients with recurrent or newly developed atrial fibrillation after TAVR surgery. The study included 1426 patients with recurrent or newly diagnosed atrial fibrillation who had conventional indications for oral anticoagulant therapy after TAVR surgery in 173 centers across 14 countries.
The results showed that after TAVR treatment, the prevention of stroke and other thromboembolic events by idoxaban was not inferior to VKA, but the incidence of major bleeding was higher. The results of this study are only applicable to elderly patients with concomitant atrial fibrillation, moderate surgical risk, and symptomatic AS, and not to younger patients with lower surgical risk, asymptomatic aortic stenosis, and patients undergoing PCI simultaneously.
Figure 10: ENVISAGE-TAVI AF research results
STEP：New evidence for strengthening blood pressure reduction in elderly patients with hypertension
The results of antihypertensive tests conducted in elderly hypertensive patients are mixed, and guidelines recommend different levels of antihypertensive targets. At the ESC 2021 conference, Professor Cai Jun from Fuwai Hospital, Chinese Academy of Medical Sciences, presented a STEP study exploring whether intensive therapy targeting systolic blood pressure (SBP)<130mmHg can reduce the risk of cardiovascular disease.
The study included 8511 elderly patients with primary hypertension from 42 clinical research centers in China, divided into an intensive treatment group (SBP<130 mmHg but ≥ 110 mmHg) and a standard treatment group (SBP 130-150 mmHg). After a median follow-up of 3.34 years, the average decrease in SBP in the intensive treatment group was 19.4 mmHg, with a relative risk reduction of 26% for the primary composite endpoint.
The SPRINT study confirmed that SBP targeting<120 mmHg has cardiovascular benefits, but it is challenging as it may lead to higher drug costs and more frequent visits, as well as a significant increase in the incidence of kidney injury. However, in the STEP study, no increase in renal injury incidence was observed for SBP targets<130mmHg.
Figure 11: Main Results of STEP Study
Looking back at the heavyweight research that emerged in the cardiovascular field in 2021, these research results have guided future research and provided more evidence-based medicine for guideline updates.
We also see that among the top ten clinical studies reviewed, two are original clinical research results from China, indicating that the quality and level of clinical research in China are constantly improving and receiving increasing recognition and attention from domestic and foreign peers. Of course, we look forward to more progress in the cardiovascular field in the future!
Source of this article: Cardiovascular Health Alliance Information Platform