Journal watch: recent studies of note

Recent studies of note.

Two-thirds of eligible heart failure patients don't get aldosterone antagonists

Fewer than one-third of patients hospitalized for heart failure are receiving aldosterone antagonist therapy as recommended by current guidelines, according to a recent study.

Researchers analyzed 43,625 heart failure (HF) patients discharged from 241 hospitals participating in the Get with the Guidelines-HF quality improvement registry between 2005 and 2007. Only 32.5% of the 12,565 patients eligible for aldosterone antagonists received them at discharge and there was wide variation in use among the hospitals. The eligible patients most likely to receive the therapy included those who were African-American, younger, had lower systolic blood pressure, had a history of implantable cardioverter-defibrillator use, had pacemaker implantation, had a history of depression or alcohol use, and had no history of renal insufficiency.

The authors noted that inappropriate and potentially in-appropriate use of therapy was rare. Aldosterone antagonists were prescribed to 0.5% of patients with documented contraindications and 2.7% of patients with high creatinine levels of 3.0 mg/dL or greater. The results appeared in the Oct. 21 Journal of the American Medical Association.

Physicians may have been slow to adopt aldosterone antagonist recommendations because the original guidelines said therapy should be considered rather than recommended, the authors said. (The guidelines were later updated.) Other factors that may have contributed to low usage include lack of monitoring by hospitals because therapy isn't a core performance measure; concerns that hyperkalemia and an increased creatinine level would extend length of stay; and lack of time to start therapy due to short length of stay for heart failure.

It is unclear whether less use of therapy in older patients represents a disparity that needs to be overcome or a safety measure, the authors said, considering that drugs that interfere with the renin-angiotensin-aldosterone system are a risk factor for hyperkalemia in elderly patients. The results of this study suggest that decreased creatinine clearance with age contributes to hyperkalemia, they continued, and that hyperkalemia monitoring may need to be based on age and baseline renal function instead of a set schedule.

The findings confirm that aldosterone antagonist therapy can be compliant with guidelines without contributing to inappropriate use, the authors concluded. Considering the efficacy of these drugs for heart failure, they urged a stronger uptake of guidelines that recommend the use of aldosterone antagonists.

The study may overrepresent high-performing hospitals who willingly participated in GWTG-HF, the authors noted.

ACE inhibitors before CABG associated with higher death rate

Angiotensin-converting enzyme inhibitors administered before coronary artery bypass grafting were associated with a higher risk of mortality, renal dysfunction and postoperative atrial fibrillation, a recent study found.

Researchers conducted a retrospective, observational cohort study on more than 10,000 consecutive patients undergoing coronary artery bypass grafting (CABG) between 1996 and 2008. The 3,052 patients who received preoperative angiotensin-converting enzyme (ACE) inhibitors had double the risk of death compared with a control group. The ACE inhibitor group also had a significantly higher risk of postoperative renal dysfunction, atrial fibrillation (AF), and increased use of inotropic support. The study was published in the Nov. 3 Journal of the American College of Cardiology.

The finding that preoperative ACE inhibitors doubled the risk of death in CABG patients is at odds with previous studies, likely because those studies had smaller sample sizes with insufficient power to detect differences in mortality, which is rare after CABG, the authors said. Other studies also have suggested that ACE inhibitors can prevent postoperative AF, the authors continued, but those studies often did not include cardiac surgery patients whereas the current study examined only patients undergoing CABG and included a much larger sample size.

Since the study was conducted in the United Kingdom, outcomes may be different in the U.S., where patients are likely to have more comorbidities, said an accompanying editorial. Another possible limitation of the study is its use of propensity score matching, which makes it difficult to determine whether ACE inhibitor therapy is an intrinsic risk factor or a marker for something else, such as severe hypertension, the editorial said.

The study authors suggested omitting ACE inhibitors before surgery and restarting them postoperatively in order to improve early outcomes while retaining the cardioprotective effects. The editorialist added that while ACE inhibitors are, on average, associated with improved outcomes, these findings suggest that they may not benefit all patients and that physicians should be alert to possible short-term, avoidable risks.

As-needed chest radiography may be best strategy in ICU

Performing chest radiography as needed, as opposed to routinely, safely reduced the number of chest radiographs in intubated and mechanically ventilated patients, a study found.

Researchers performed a cluster-randomized, open-label crossover study in which 21 intensive care units in France were assigned to alternate between a routine and on-demand strategy for chest radiography over two treatment periods, each spanning 20 consecutive patients. Overall, there was a 32% reduction in chest radiographs with the on-demand strategy, with no negative effects on patients' quality of care or safety. The study was published online Nov. 5 in The Lancet.

The authors noted that many intensivists are not yet comfortable with the on-demand strategy because routine radiography is done to ensure that important findings are not missed. The current study did not investigate a possible link between daily radiographs and missed findings, they said, but did show that an on-demand strategy did not change the number of radiographs that led to interventions and did not increase time spent on ventilation, ICU length of stay or mortality.

The study provides “persuasive evidence” that routine radiographs are not necessary in most intubated and mechanically ventilated patients, the editorial continued. The on-demand strategy appears to be justified, the editorial concluded, only if the following conditions are met:

  • Skilled clinicians are on hand to identify patients requiring chest radiographs;
  • Images can be made and interpreted efficiently; and
  • Abnormalities can be acted on throughout the day.

High CRP levels may predict adverse outcomes after stent implantation

Elevated C-reactive protein levels in patients implanted with drug-eluting stents are associated with an increased risk of stent thrombosis, death and myocardial infarction, a study found.

Researchers conducted a prospective study on 2,691 patients who received drug-eluting stents (DES). After a median follow-up of 3.9 years, elevated C-reactive protein (CRP) levels were associated with a significantly increased risk of stent thrombosis (hazard ratio [HR], 3.86) and significantly predicted the risks of death (HR, 1.61) and myocardial infarction (HR, 1.63). The results were published in the Nov. 17 Circulation.

The study is the first to suggest an association between CRP and DES-related stent thrombosis, the authors said, and should raise concerns about the long-term safety of DES. They pointed out that the study included real-world patients with off-label use of DES, as opposed to patients in a clinical trial. Possible explanations for the association, the authors speculated, may be CRP's association with other potential causes of DES-related thrombosis, such as platelet and clotting system activation and endothelial dysfunction.

The authors acknowledged that, since stent thrombosis is relatively infrequent, the results should be tested in larger studies with longer follow-up. Also, the study did not address bare metal stents, so the application of elevated CRP levels to guide specific stent selection for reducing stent thrombosis may be limited. In addition, the study did not address the clinical value of lowering CRP levels and so does not confirm a direct benefit of reducing CRP after DES implantation.

The findings suggest that inflammatory risk assessment with CRP may be useful for identifying patients at high risk for adverse outcomes, the authors said. The study also raises the possibility that certain cardiovascular drugs, including statins, aspirin glycoprotein inhibitors, thiazolidinediones and beta-blockers, may reduce the risk of DES-related thrombosis, a hypothesis that calls for further study.

Antivirals after 48 hours may help hospitalized H1N1 patients

U.S. patients hospitalized with 2009 H1N1 influenza last spring appeared to benefit from antiviral therapy even when it was received after 48 hours, a recent study suggested.

Researchers examined the medical charts of 272 U.S. patients who were hospitalized for at least 24 hours for influenza-like illness (temperature of 100°F or higher, and cough or sore throat), and who tested positive for the 2009 H1N1 virus using a real-time reverse-transcriptase polymerase chain reaction assay. Testing was performed by either the CDC or one of 24 state health departments; illness onset ranged from April 1, 2009 to June 5, 2009. These patients represent 25% of those hospitalized with the illness whose cases were reported to the CDC between May 1 and June 9, 2009. The study was published in the Nov. 12 New England Journal of Medicine.

Forty-five percent of patients were children under 18 years old, while 5% were at least 65 years old. Seventy-three percent of patients had one or more underlying medical conditions, including asthma, diabetes and pregnancy, as well as heart, lung and neurologic diseases. Of 249 patients who had chest radiography, 40% had findings consistent with pneumonia. Twenty-five percent of the patients were admitted to an ICU, and 28% of those admitted to an ICU (19 patients) died. The median age of those who died was 26 years (range, 1.3 years to 57 years), and the median time from onset of illness to death was 15 days (range, 4 days to 52 days).

Data on the use of antiviral drugs were available for 268 patients. Of these, 75% began antiviral therapy at a median of three days after illness onset, though 39% received it within 48 hours of symptom onset. Of the 19 patients who died, 90% received antivirals and all received antibiotics; the median time from their illness onset to antiviral initiation was eight days. No patients who died had received antivirals within 48 hours of symptom onset.

Though quick initiation of antiviral therapy is clearly preferable, these study data suggest use of antivirals is beneficial for patients with suspected 2009 H1N1 infection even beyond 48 hours after symptom onset, and especially for patients with pneumonia, the authors said. Study limitations include the fact that it was voluntary and thus subject to reporting bias; that it included only patients with confirmed H1N1 (and not those who may have had it but were untested); and that tests weren't obtained in a standardized manner.