Both Dosing Safety, Guideline-Based Use of Antithrombotics Related to NSTE-ACS Outcomes

Hospitals vary widely in their appropriate dosing of antithrombotics and adherence to guideline-recommended therapies for patients with NSTE-ACS, according to a registry study published online February 16, 2015, ahead of print in Circulation. While there was little correlation between safety and adherence profiles, in-hospital clinical outcomes were better in centers with higher marks in both categories.Take Home: Both Dosing Safety, Guideline-Based Use of Antithrombotics Related to NSTE-ACS Outcomes

“These findings [support] the need for broader metrics of quality that should include not only measures of compliance with guideline-based care but also that of hospital safety as promoted by the Institute of Medicine,” the authors write.

Researchers led by Rajendra H. Mehta, MD, MS, of the Duke Clinical Research Institute (Durham, NC), looked at outcomes among 39,291 high-risk patients with ischemic symptoms at rest treated at 283 US centers participating in the CRUSADE national quality improvement initiative between January 2004 and June 2005. Hospitals were assessed based on their adherence to then-current American College of Cardiology (ACC)/American Heart Association (AHA) 2002 Class I guideline-recommended therapies and safety performance—defined as appropriate dosing of IV heparins or glycoprotein IIb/IIIa inhibitors (GPIs). Hospital composite adherence scores and the composite safety metric were defined as the ratio of total received therapies (or total who received appropriate dose) for all patients out of the total number of opportunities for all patients.

The overall composite median adherence rate for guideline-recommended therapies over the study period was 85%, and the median hospital safe drug-dosing rate was 53%. These rates were minimally—but significantly—associated with each other (P = .008).

Patients treated at hospitals with low adherence and safety were older, more likely to be female and have diabetes and prior congestive heart failure, and less likely to be treated by a cardiologist. Additionally, hospitals in this category were smaller and more likely to lack the capabilities to perform percutaneous or surgical coronary revascularization.

In addition, patients treated at these hospitals were less likely than those at hospitals with high safety and adherence to receive guideline-based therapies, including aspirin and beta-blockers, within 24 hours of admission and at discharge; GPIs within 24 hours; and ACE inhibitors or angiotensin receptor blockers, clopidogrel, and statins at discharge. Overdosing of heparins and GPIs was also more common at these institutions.

Hospital guideline adherence was inversely associated with in-hospital mortality: for every 10% increase in adherence, mortality risk fell by 39% (OR 0.61; 95% CI 0.50-0.75). Also, for every 10% increase in appropriate dosing, mortality fell by 18% (OR 0.82; 95% CI 0.73-0.93). These patterns persisted after adjustment for potential confounders.

Compared with hospitals with low safety and adherence, those with high marks in only one of those categories had intermediate risk-adjusted mortality rates.

While increased guideline-based adherence was associated with a greater risk of non-CABG major bleeding (adjusted OR for every 10% improvement 1.25; 95% CI 1.08-1.44), improved dosing safety was associated with a lower risk (adjusted OR for 10% improvement 0.93; 95% CI 0.87-0.98).

Results were similar in a sensitivity analysis excluding patients from hospitals with CABG capabilities, with lowest mortality in the high-adherence and high-safety group.

‘Strike a Balance’

Dr. Mehta and colleagues write that there is more to quality of care than merely guideline adherence, but despite growing awareness of this, “the association between hospital use of guideline-based therapy and patient safety as well as their association with in-hospital outcomes remain less known.”

The current results show that hospitals with good adherence to guideline-recommended therapies did not necessarily have stellar safety records, and vice versa, they write, adding that only paying attention to guideline adherence and shortchanging safety efforts could be “potentially dangerous” for hospitals in that it can lead to higher major bleeding rates.

Going forward, hospitals should strive to “strike a balance and perhaps focus also on patient safety and not just use of evidence-based therapies,” the authors suggest. “Doing the right things and doing them right had the best chance of being associated with improved patient outcomes and perhaps represented a better surrogate of ‘quality’ rather than just guideline-based therapies or safety alone.”

The best way to do this, they say, would be to measure improvement in both categories, especially in high-risk patients. “In [the] future, research efforts should be directed to explore feasibility of developing a standardized composite matrix incorporating both guideline adherence and proper dosing of high-risk medications that would have the best correlation with outcomes,” the authors conclude.

Physician Participation Vital to Change

When it comes to patient safety and guideline adherence, “one cannot automatically assume both are happening,” Thomas H. Lee, MD, MSc, of Brigham and Women’s Hospital (Boston, MA), writes in an accompanying editorial. “There are errors of omission and errors of commission—and both worsen patient outcomes.”

Dr. Lee, who is also the chief medical officer for Press Ganey, supports new measurement and improvement methodologies across the board, starting with measuring “actual patient outcomes.” Though clinicians have avoided such efforts because of difficulties with risk adjustment and factors beyond their control, he writes, “the real focus of health care is the welfare of patients, not the reliability of providers…. Knowing that their outcomes are mediocre is likely to make improvement much more compelling for the process measures [for which] the institution is below average.”

Additionally, all outcomes should be measured and reported, he says, as “no one outcome tells the story for any subset of patients.” When institutions understand their deficiency in outcomes like mortality, “that should precipitate an all-hands-on-deck effort to dissect whether patient selection, poor guideline adherence, or suboptimal safety are causing the gap.”

But to move forward, “new methods are needed to motivate clinicians to care about these outcomes and process metrics,” Dr. Lee says, citing the “relentless demands” on clinicians’ time and emphasizing the challenge of process changes. “[I]f physicians in particular are not engaged in the process of improvement, much of the data collection for quality improvement [is] pointless.”


1. Mehta RH, Chen AY, Alexander KP, et al. Doing the right things and doing them the right way: the association between hospital guideline adherence, dosing safety, and outcomes among patients with acute coronary syndrome. Circulation. 2015;Epub ahead of print.

2. Lee TH. Performance metrics as drivers of quality: getting to second gear [editorial]. Circulation. 2015;Epub ahead of print.

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  • CRUSADE was funded by Millennium Pharmaceuticals and Schering Corporation with additional support from the Bristol-Myers Squibb/Sanofi Pharmaceuticals partnership.
  • Dr. Mehta reports no relevant conflicts of interest.
  • Dr. Lee reports serving as chief medical officer for Press Ganey.

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