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Simvastatin, atorvastatin cut mortality risk for sepsis patients

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The Taiwan connection – as good as it gets

The statin-sepsis mortality link will probably never be definitively proven, but the study by Lee and colleagues gives us the best data so far on this intriguing connection, Steven Q. Simpson, MD and Joel D. Mermis, MD wrote in an accompanying editorial.

“It is unlikely that prospective randomized trials of statins for prevention of sepsis mortality will ever be undertaken, owing to the sheer number of patients that would require randomization in order to have adequate numbers who actually develop sepsis,” the colleagues wrote. “We believe that the next best thing to randomization and a prospective trial is exactly what the authors have done – identify a cohort, track them through time, even if nonconcurrently, and match cases to controls by propensity matching on important clinical characteristics.”

Nevertheless, the two said, “This brings us to one aspect of the study that leaves open a window for some doubt.”

Lee et al. extracted their data from a large national insurance claims database. These systems “are commonly believed to overestimate sepsis incidence,” Dr. Simpson and Dr. Mermis wrote. A 2009 U.S. study bore this out, they said. “That study showed that in the U.S in 2014, there were approximately 1.7 million cases of sepsis in a population of 330 million, for an annual incidence rate of five sepsis cases per 1,000 patient-years.”

However, a “quick calculation” of the Taiwan data suggests that the annual sepsis caseload is about 5,200 per year in a population of 23 million at risk – an annual incidence of only 0.2 cases per 1,000 patient-years.

“This represents an order of magnitude difference in sepsis incidence between the U.S. and Taiwan, providing some issues to ponder. Does Taiwan indeed have a lower incidence of sepsis by that much? If so, is the lower incidence related to genetics, environment, health care access, or other factors?

“Although Lee et al. have provided us with data of the highest quality that we can likely hope for, the book may not be quite closed, yet.”

Dr. Mermis and Dr. Simpson are pulmonologists at the University of Kansas, Kansas City. They made their comments in an editorial published in the April issue of CHEST® (Mermis JD and Simpson SQ. CHEST. 2018 April. doi: 10.1016/j.chest.2017.12.004.)



Of the entire cohort, 17% died by 30 days and nearly 23% by 90 days. Compared with those who had never received a statin, the statin users were 12% less likely to die by 30 days (hazard ratio, 0.88). Mortality at 90 days was also decreased, when compared with nonusers (HR, 0.93).

Simvastatin demonstrated the greatest benefit, with a 28% decreased risk of 30-day mortality (HR, 0.72). Atorvastatin followed, with a 22% risk reduction (HR, 0.78). Rosuvastatin exerted a nonsignificant 13% benefit.

The authors then examined 90-day mortality risks for the patients with a propensity matching score using a subgroup comprising 536 simvastatin users, 536 atorvastatin users, and 536 rosuvastatin users. Simvastatin was associated with a 23% reduction in 30-day mortality risk (HR, 0.77) and atorvastatin with a 21% reduction (HR, 0.79), when compared with rosuvastatin.

Statins’ antimicrobial properties are probably partially caused by their inactivation of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase pathway, Dr. Lee and his colleagues noted. In addition to being vital for cholesterol synthesis, this pathway “also contributes to the production of isoprenoids and lipid compounds that are essential for cell signaling and structure in the pathogen. Secondly, the chemical property of different types of statins may affect their targeting to bacteria. The lipophilic properties of simvastatin or atorvastatin may allow better binding to bacteria cell walls than the hydrophilic properties of rosuvastatin.”

The study was funded by the Taiwan National Science Foundation and Taiwan National Ministry of Science and Technology. Dr. Lee had no financial conflicts.

SOURCE: Lee C-C et al. CHEST 2018 April;153(4):769-70


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