Journal watch: Recent studies of note

Recent studies about induced hypothermia after cardiac arrest, atherosclerosis before ACS hospitalization, and other topics.

Benefits of induced hypothermia after cardiac arrest outweigh costs

Therapeutic hypothermia improves survival and neurological outcomes and is cost-effective in treating comatose cardiac arrest survivors, a recent study found.

Using published data, as well as input from cooling device companies and resuscitation experts, researchers developed a decision model to capture costs and outcomes for patients with witnessed out-of-hospital ventricular fibrillation arrest who met inclusion criteria for the Hypothermia After Cardiac Arrest (HACA) trial. In the model, patients who received therapeutic hypothermia with a cooling blanket gained an average of 0.66 quality-adjusted life-year (QALY) compared with conventional care, yielding an incremental cost-effectiveness ratio of $47,168 per QALY. The study appeared in the September 2009 Circulation: Cardiovascular Quality and Outcomes.

The use of hypothermia has been limited due to concerns that the benefits of treatment do not justify the cost and that hypothermia may raise the risk of poor neurological outcomes in survivors. In this study, hypothermia therapy remained cost-effective (less than $100,000 per QALY) even if a hospital had only one eligible patient for hypothermia treatment per year and survivors accrued considerable post-resuscitation care costs, the authors said. While acknowledging that their study was limited by its small sample size (a single trial with fewer than 400 patients who met inclusion criteria), the authors concluded that, from a societal perspective, the benefits of post-arrest hypothermia justify its costs.

Atherosclerosis before ACS hospitalization raises mortality risk

Patients who had atherosclerosis prior to hospitalization for acute coronary syndrome (ACS) are more likely to die and less likely to receive recommended treatments, according to a recent study.

Researchers analyzed treatment and outcomes for 143,999 patients who were hospitalized for acute coronary syndrome between 2000 and 2008. Overall in-hospital mortality was 5.3%, but the risk increased with the number of prior artery blockages a patient had; for example, those with no prior blockage had a 4.7% risk of death compared to 9.1% for patients who had prior disease in all three vascular territories (P<0.001). The patients with prior disease were also older and had more comorbidities.

The patients with greater prior disease were also less likely to receive coronary revascularization, smoking cessation counseling, lipid-lowering therapy and angiotensin-converting enzyme (ACE) inhibitors. The lower rates of revascularization may be due to a lack of options in patients with diffuse coronary artery disease, the difficulty of vascular access, or the higher risk of complications, the study authors suggested.

The reduced use of smoking cessation and evidence-based drug therapies in sicker patients is counterintuitive, the authors said. Higher-risk patients would receive the greatest absolute benefit from compliance with the guideline-recommended treatments. Possible explanations for the disparity include greater comorbidities or drug interactions in these patients, a sense of futility, or economic issues. Patients with prior disease were more likely to be on Medicaid, the study found.

All groups were equally and very likely to receive aspirin (92% of the time) and beta-blockers (94% to 95% of the time) in accordance with guidelines. The researchers wrote that patients with prior vascular disease would benefit from targeted interventions to improve compliance with the other recommended care. The study was published online by Circulation on Aug. 3.

Palliative care program improves mood but not symptoms

A palliative care intervention improved mood and quality of life for patients with advanced cancer, although it did not affect their symptoms or use of medical services in a recent trial.

Participating patients had been diagnosed with life-limiting cancer 8 to 12 weeks before they entered the study and had been given a prognosis of approximately one year. The 322 patients were randomized to either usual care or an intervention conducted by advanced practice nurses with palliative care training. The intervention included four initial educational and problem-solving sessions followed by telephone follow-up at least monthly. Patients were also invited to shared medical appointments led by a palliative care physician. The study was conducted in rural New Hampshire and Vermont.

All study participants completed questionnaires about their quality of life, symptom intensity and mood every three months until death or study completion. Overall, patients in the intervention group had higher quality of life scores (P=0.02) and less depressed mood (P=0.02) but an insignificant improvement in symptom intensity (P=0.06). Patients who died during the study had similar results to the overall group. There was no difference in the number of hospital days, ICU days or emergency department visits between groups.

Study authors noted that they could not meet their original target significance level of 0.01 since they did not achieve the planned enrollment of 400 patients. They also could not determine why mood and quality of life improved without any change in symptom intensity. Overall, patients in the study reported relatively low symptom intensity so it may have been difficult for the intervention to have much more effect on symptoms, the authors suggested. The intervention might also have had greater effect if it had been conducted in person rather than by phone, but that was not feasible in the rural study location.

Despite the study's limitations, the researchers did conclude that an early palliative care intervention for patients with advanced cancer can improve quality of life and mood, two high-priority patient-centered goals. The research was published in the Aug. 19 Journal of the American Medical Association.

Early exercise training in the ICU could aid functional recovery

Early use of a bedside cycle ergometer may enhance recovery of functional exercise capacity in ICU patients, a study recently reported.

Belgian researchers performed a randomized, controlled trial in 90 patients at a single center's medical and surgical ICU to determine whether daily exercise on a bedside cycle ergometer would improve functional recovery. Forty-five patients were assigned to the control group, which received respiratory physiotherapy and a daily session of standardized passive or active motion for upper and lower limbs, and 45 were assigned to the exercise group, which received the control therapy plus one 20-minute active or passive exercise training session daily on a bedside ergometer. Patients were included as soon as their cardiorespiratory condition allowed them to participate in a cycling session. The researchers measured quadriceps force and functional status at both ICU and hospital discharge and six-minute walking distance at hospital discharge only. The study results appeared in the September Critical Care Medicine.

Sixteen percent of patients in the control group and 24% of patients in the exercise group died while in the hospital (P=0.29). Only data from survivors were analyzed. At discharge from the ICU, the control and exercise groups did not differ in quadriceps force or functional status. However, at hospital discharge, the patients in the treatment group were found to have significantly better six-minute walking distance, isometric quadriceps force and functional well-being as measured by the physical functioning item of the Short Form-36 Health Survey (P<0.05). No patients in the exercise group reported adverse outcomes associated with the ergometer sessions.

The authors acknowledged their study's limitations, including that the exercise group received about 20 more minutes of exercise per day than controls. However, they concluded that “an individually tailored exercise protocol” is feasible in critically ill ICU patients and that such a protocol, when begun early in a prolonged stay, may improve functional outcome at hospital discharge.

ACS treatments analyzed

A recent paper examined the safety, efficacy and timing of antiplatelets and antithrombotics in acute coronary syndromes, highlighted controversies and looked at the most promising new drugs in late-stage development. The analysis, published online and in the Sept. 8 Journal of the American College of Cardiology, includes the following observations:


  • Data support intravenous glycoprotein IIb/IIIa inhibitors (GPIs) for moderate- or high-risk non-ST-segment elevation ACS (NSTE-ACS), especially in early invasive strategy. Those presenting with ST-segment elevation myocardial infarction (STEMI) who have percutaneous coronary intervention (PCI) also may benefit. For low-risk ACS, GPIs could be harmful in troponin-negative patients under conservative management or those with elevated bleeding risk.
  • Clopidogrel plus aspirin appears beneficial and safe in patients with STEMI, although there are no safety data with a loading dose for elderly patients receiving fibrinolytics or in patients with STEMI managed without reperfusion therapy.
  • Benefits of early pre-loading with clopidogrel within five days of surgery appear to outweigh perioperative bleeding risks.
  • Prasugrel has a protective effect in ACS patients and may reduce stent thrombosis, but it may increase major bleeding in patients with a history of stroke or transient ischemic attack, patients age 75 or older and those weighing less than 60 kg.


  • Low-molecular-weight heparin (LMWH) is superior to short-term unfractionated heparin (UFH) in conservative management of NSTE-ACS, but questions remain about its use in certain settings, including an early invasive strategy, rapid transitions to catheterization lab, procedural anticoagulation and in conjunction with fibrinolytic therapy for patients with STEMI.
  • Adding UFH to enoxaparin in an uncontrolled fashion may result in increased bleeding complications.
  • Continued in-hospital administration of enoxaparin may provide substantial additional benefit in patients with STEMI.
  • Overall, LMWH appears to be a viable option across a wide spectrum of patients presenting with ACS, suggesting that it should be investigated further for potential use in other settings such as primary PCI for acute MI.
  • The factor Xa inhibitor fondaparinux seems to reduce the risk of bleeding and lowers long-term morbidity and mortality compared with enoxaparin in NSTE-ACS, although there were more catheter-related thrombi. However, fondaparinux appears to be associated with a risk of harm (increased rate of coronary complications) in STEMI patients treated with primary PCI.
  • Promising drugs in the pipeline include novel anticoagulants that inhibit propagation of coagulation by targeting factor IXa, Xa or their cofactors. These agents are based upon aptamer technology, which addresses control and reversibility in acute care settings and could play a crucial role during and after cardiopulmonary bypass for coronary surgery and other situations where bleeding occurs. However, the authors noted that long-term investments are needed to gain clinical and regulatory acceptance of these new drugs.