ABSTRACT

BACKGROUND Shenfu injection, as a traditional Chinese medicine, can alleviate reperfusion injury after ST-segment elevation myocardial infarction (STEMI) through multiple pharmacologic effects. This trial aimed to evaluate the effect of Shenfu injection on myocardial injury in STEMI patients undergoing primary percutaneous coronary intervention (PCI).

METHODS This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. First-time anterior STEMI patients undergoing primary PCI within 12 hours of symptom onset due to a proximal or mid left anterior descending artery occlusion were randomized 1:1 to receive either intravenous Shenfu injection or placebo before reperfusion and followed by once a day until 5 days after primary PCI. The primary endpoint was infarct size by cardiac magnetic resonance (CMR) at 5 days after randomization.

RESULTS A total of 295 patients were randomized with evaluable CMR in 273 patients. Infarct size (37.4±14.1% vs 37.5±14.5%; effect size −0.04%, 95% confidence interval: −3.45, 3.37; P=0.982) did not differ between the Shenfu injection and placebo groups. This was true for other CMR parameters. The area under curve for creatine kinase-myocardial band did not differ between groups. The incidences of thrombolysis in myocardial infarction (TIMI) flow grade 3 (94.8% vs 97.1%, P=0.324), TIMI myocardial perfusion grade 3 (91.7% vs 92.1%, P=0.914), and ST-segment resolution ≥70% (25.4% vs 26.1%, P=0.906), were also similar between groups. Adverse events were evenly distributed across groups.

CONCLUSIONS For patients with anterior STEMI undergoing primary PCI, administration of Shenfu injection was safe but did not reduce infarct size by CMR.

What Is New?

Among 295 anterior ST-segment elevation myocardial infarction patients randomized to intravenous Shenfu injection or placebo, the primary analysis demonstrated that the infarct size revealed by cardiac magnetic resonance was 37.4 % in the Shenfu injection group and 37.5% in the placebo group, a difference that was not statistically significant.

For patients with anterior ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, administration of Shenfu injection was safe and well tolerated.

What Are the Clinical Implications?

Cardiovascular clinicians need to realize that successful cardioprotective therapies may require synergistic multitarget approaches.

Future clinical trials are required to investigate the use of additive cardioprotective strategies in patients with large infarcts or severe hemodynamic alterations (eg. concomitant heart failure or cardiogenic shock).

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04493840.

Funding Statement

This study is financed by research grant from China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. and partially funded by National Key R&D Program of China (2022YFC2505600), Beijing Municipal Natural Science Foundation Grant (JQ24039), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (ZLRK202318), and Beijing Municipal Science & Technology Commission, China (Z221100003522027).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This trial was approved by the Institutional Review Board of Beijing Anzhen Hospital, Capital Medical University (2019013) and the institutional review committee at each clinical center. This trial was registered at ClinicalTrials.gov (NCT04493840).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Data are not currently available. Will data be available: Yes Where: Electronic repository When will data availability begin: Date to be confirmed by the corresponding author.

Nonstandard Abbreviations and AcronymsAEadverse eventCMRcardiac magnetic resonanceLADleft anterior descendingLVleft ventricularMACCEmajor adverse cardiovascular and cerebrovascular eventPCIpercutaneous coronary interventionSAEserious adverse eventSTEMIST-segment elevation myocardial infarctionTIMIthrombolysis in myocardial infarction