Prompt Postsurgical Resumption of ARBs May Drop Mortality Risk

Yael Waknine

June 04, 2015

Prompt resumption of angiotensin receptor blocker (ARB) therapy after surgery slashes 30-day mortality risk, particularly among younger patients, according to a national cohort study published online June 4 in Anesthesiology.

Although clinicians commonly discontinue ARBs before surgery to prevent intraoperative hypotension, there is little evidence to guide optimal timing for resumption of therapy, write lead author Susan Lee, MD, from the University of California, San Francisco, and colleagues.

Researchers therefore reviewed data for 30,173 admissions to the Veteran Affairs Healthcare system for 25,663 patients who were taking ARBs and undergoing noncardiac surgical procedures between 1999 and 2011. In approximately one third (33.8%) of cases, ARBs had not been reinstated by postoperative day 2.

Results revealed that the delay in resumption of ARB therapy was linked to a more than twofold increase in the 30-day all-cause mortality rate (3.2% vs 1.3%; hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.47 - 2.06; P < .001) after adjustment for age, sex, year of surgery quartile, comorbidities, and surgical as well as early postoperative factors.

Moreover, the increased mortality risk remained even when the analysis was restricted to a propensity score-matched subset of 19,490 patients (HR, 1.47; 95% CI, 1.22 - 1.78; P < .001), which accounted for factors such duration of surgery, emergency surgery, and early postoperative elevated creatinine and troponin elevations.

The researchers also found that delays in resumption of ARBs were linked to an increased risk for noncardiac complications (P < .001), driven by increased rates of renal failure, pneumonia, and sepsis (absolute difference, <1% to 2%). Although heart failure was more common among patients who did not resume ARBs (P = .02), there was no statistically significant difference in overall cardiac complications between groups.

The authors point out that whereas postoperative day 2 was selected as a convenient point to enable assessment of ARB resumption during inpatient stay, the results remained consistent when sensitivity analyses were performed at other points (days 1, 7, and 14).

Noting that the ARB attrition rate was higher than that of prior studies (10%), the authors suggest that contributing factors may include clinician apprehension regarding risks for hypotension and acute kidney injury, as well as inadvertent discontinuation of therapy during multiple transitions in care.

Mortality Risk Higher in Younger Patients

Although mortality risk was increased across all population subgroups, the effect of withholding ARB therapy was higher among patients younger than 60 years (HR, 2.52; 95% CI, 1.69 - 3.76; P < .001) compared with those older than 75 years (HR, 1.42; 95% CI, 1.09 - 1.85; P = .01).

When age was modeled as a continuous variable, the HR for 30-day mortality associated with delayed vs prompt return to ARB therapy was 1.89 (95% CI, 1.56 - 2.28) at the cohort mean age of 67 years, and decreased by a factor of 0.85 for each decade increase in age, to yield an HR of 2.22 (95% CI, 1.65 - 2.99) at age 57 years and only 1.60 (95% CI, 1.33 - 1.94) at age 77 years.

According to the authors, the effect may be in part a result of an increased inflammatory response to stress among younger patients dependent on medical control of risk factors for major cardiovascular events. Prompt resumption of ARB therapy in this population can attenuate the effects of inflammation, reducing microvascular injury and organ dysfunction.

The study is limited by the possibility that ARB withholding may have been intentional in some cases, particularly in the sickest patients at greatest risk for death. Similarly, ARBs may have been inadvertently withheld during postoperative transitions of care.

"It is possible that failure to restart ARB and mortality are common effects of unmeasured aspects of being frail or sick. Therefore, although we were able to find strong associations between ARB withholding and 30-day postoperative mortality, given the retrospective observational nature of the data, we are unable to make statements of causality. Future prospective randomized studies will be helpful in furthering our understanding of this association," the authors write.

In the interim, "careful attention to resuming regularly prescribed medications in the postoperative period may reduce mortality, particularly in younger patients," the authors conclude.

The authors have disclosed no relevant financial relationships.

Anesthesiology. Published online June 4, 2015.

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