Inotropes and mortality in patients with cardiogenic shock: An instrumental variable analysis from the SWEDEHEART registry

Background The use of inotropic agents in treating cardiogenic shock (CS) remains controversial. We aimed to investigate the effect of treatment with inotropes on 30-day mortality in patients with CS from the SWEDEHEART registry (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies). Methods We used data from the national SWEDEHEART registry on all patients diagnosed with CS in Sweden between 2000 and 2022. The primary endpoint was 30-day all-cause mortality. We used multilevel Cox proportional-hazards regression with instrumental variable and inverse probability weighting propensity score to adjust for known and unknown confounders. The treatment-preference instrument was the quintile of preference for using inotropes at the treating hospital. Results In total, 16,214 patients (60.5% men and 39.5% women) were included; 23.5% had diabetes, 10.2% had a previous myocardial infarction (MI), and 13.8% had previous heart failure (HF). The median age was 70 years (interquartile range; 19), and 66.4% were >70. Acute coronary syndrome (ACS) was the cause of CS in 82.9% of patients. Inotropic agents were used in 43.8% of patients, while 56.2% did not receive inotropic agents. There were 7,875 (48.1%) deaths. On average, patients treated with inotropes were two years younger and more likely to have ACS. Patients not treated with inotropes were more likely to have previous MI and previous PCI but less likely to undergo PCI. The number of patients with CS decreased by 12% per year (Ptrend<0.001). There was a considerable variation between hospitals in the preference for using inotropes ranging from 25 to 78% (P<0.001). Inotropes increased by 5% per year (Ptrend<0.001). The unadjusted mortality in CS increased by 2% per calendar year (Ptrend<0.001). The risk of death was higher in patients treated with inotropes [adjusted hazard ratio (HRadj) 1.72; 95% confidence interval (CI) 1.26-2.35; P=0.001]. There was a quantitative interaction between inotrope treatment and age and diagnosis (Pinteraction < 0.001 and Pinteraction = 0.018, respectively). Conclusions In this observational study, using inotropes was associated with a higher mortality risk in patients with CS. The increased risk of death was more pronounced in patients younger than 70. The number of patients with CS is decreased, while the use of inotropes and mortality increased in Sweden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement N/A ### 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: Swedish Ethical Review Authority 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 are not available to the general public due to the Swedish laws and regulations.