Journal watch: Recent studies of note

Recent studies about statins use before stroke, heparin dose after STEMI, and other topics.


Statins before stroke associated with intracranial hemorrhage after intra-arterial thrombolysis

Use of statins before ischemic stroke was associated with intracranial hemorrhage following intra-arterial thrombolysis, a recent study reported.

Researchers analyzed 311 patients (mean age 63 years) who received intra-arterial thrombolysis with urokinase following stroke. Patients with intracranial hemorrhage (ICH) were more often pretreated with statins (30% vs. 15%; P = 0.005), more often had atrial fibrillation (45% vs. 30%; P = 0.016), had more severe strokes (mean NIH Stroke Scale score 16.5 vs. 14.7; P = 0.022) and were less likely to have good collaterals (16% vs. 24%; P = 0.001). Cholesterol and triglyceride levels at admission were not associated with bleeding. However, more of the statin users were on antiplatelet therapy (65.5% vs. 16.6%; P < 0.001). The results were published online March 5 in the journal Stroke.

Prior statin use was not associated with clinical outcomes after three months, researchers concluded, suggesting that statin use should not influence which patients receive thrombolytic therapy and that statins should not be withdrawn after thrombolysis. Researchers acknowledged as limitations the study's small sample size and its observational nature. They also noted that other risk factors for intracranial hemorrhage, such as blood pressure and blood glucose level, may have played a role and that patients pretreated with statins may have been sicker and more prone to bleeding.

Weight-based nomograms not always effective in determining heparin dose after STEMI

Weight-based nomograms to determine unfractionated heparin (UFH) dose after ST-segment elevation myocardial infarction (STEMI) are not always effective, especially in some patient groups, according to a recent study.

Researchers used data from 6,055 patients in the ExTRACT-TIMI 25 trial to examine whether patient characteristics were related to the effectiveness of anticoagulation with UFH when dose was determined by weight-based nomograms. The study results appear in the March 10 Circulation.

Weight-based nomograms were followed closely “with nearly perfect adherence” when determining UFH dose. However, only 33.8% of initial activated partial thromboplastin times (aPTTs) were therapeutic, while 13.2% indicated marked underanticoagulation and 16.3% indicated marked overanticoagulation. Patients were more likely to have high aPTTs if they were older, were women, weighed less or had renal dysfunction. High aPTTs were associated with a higher risk for bleeding by 48 hours, while low aPTTs were associated with higher risk for fatal or nonfatal reinfarction by 48 hours.

The authors acknowledged that their study included data mainly from white patients and did not examine all variables that can affect response to UFH. However, they concluded that weight-based nomograms are imperfect tools for determining unfractionated heparin dose, especially in certain patient groups. “These data suggest that dosing of UFH to support fibrinolysis may need to be tailored on the basis of factors besides weight alone,” they wrote. The authors also suggested that anti-Xa assays, if they could be reported in a timely manner, might offer advantages over aPTT.

Short-term discontinuation of antiplatelet therapy may be safe in patients with drug-eluting stents

Discontinuing antiplatelet therapy may be safe in the short term in patients with drug-eluting stents, according to a systematic review.

Antiplatelet therapy is often discontinued before surgery in patients with drug-eluting stents, but doing so is the dominant risk factor for late (30 days to one year) or very late (greater than one year) stent thrombosis. Canadian researchers reviewed published studies to determine how short-term discontinuation of antiplatelet therapy affected risk in this population. One hundred sixty-one cases of late or very late stent thrombosis were identified in 84 articles. Eighty-eight percent of patients were male, and the mean age was approximately 58 years. The study results were published early online March 16 by Circulation.

Overall, 19 cases of late or very late stent thrombosis were seen in patients currently receiving dual antiplatelet therapy. In patients who stopped both antiplatelet drugs simultaneously and in those who stopped acetylsalicylic acid (ASA) and had previously stopped a thienopyridine, the median time to event was seven days. In contrast, patients who stopped a thienopyridine but continued taking ASA had a median time to event of 122 days. Events were much more likely to occur within 10 days in patients who stopped taking both drugs (36 of 48, 75%) than in those who stopped only thienopyridine but continued taking ASA (6 of 94, 6%).

Although the authors noted their study's limitations, including its observational (case-only) nature, they concluded that short-term discontinuation of thienopyridine may be relatively safe in patients with drug-eluting stents if they continue to take ASA. They stressed, however, that any decision to alter therapy needs to consider the individual patient's circumstances, balancing higher risk for late stent thrombosis against risk for bleeding during surgery.

ANP, sodium bicarbonate can protect against contrast-induced nephropathy

The risk of contrast-induced nephropathy (CIN) following coronary angiography can be reduced by the administration of atrial natriuretic peptide (ANP), a recent study found.

The prospective, randomized trial included 254 consecutive Japanese patients who had serum creatinine concentrations of at least 1.3 but less than 6 mg/dL. Beginning four to six hours before angiography, the patients received either ANP at 42 ng/kg per minute plus Ringer's lactate solution at 1.3 mL/kg per hour, or Ringer's lactate alone. Treatment continued for the next 48 hours. The study was released early online March 17 and appeared in the March 24 issue of the Journal of the American College of Cardiology.

The intervention group had significantly lower rates of CIN (which was defined as an increase in creatinine of 25% or 0.5 mg/dL over baseline within 48 hours). In the ANP group, 3.2% developed CIN compared with 11.7% of controls. The protective effect was maintained over the next month. Independent predictors of CIN risk were whether ANP was given and the use of more than 155 mL of contrast medium, the study found.

Study authors concluded that along with hydration, ANP administration is effective in prevention of CIN. The dose and duration of infusion can also determine the effectiveness of the drug, an accompanying editorial noted. The editorialist recommended that a large, multicenter, randomized, controlled study with additional clinical end points be conducted to confirm these findings.

In addition, a recent systematic review concluded that hydration with sodium bicarbonate may be superior to normal saline in reducing the incidence of CIN. The review included 12 randomized trials conducted between 1966 and 2008 that compared hydration with sodium bicarbonate with normal saline with or without N-acetylcysteine. Sodium bicarbonate significantly decreased the risk of CIN without a significant difference in the need for renal replacement therapy, in-hospital mortality or congestive heart failure. The results appeared in the April American Journal of Kidney Diseases.

The authors said their results suggest that sodium bicarbonate does not lead to worsening congestive heart failure or acute pulmonary edema, even though most participants in the trials had undergone coronary angiography, and presumably had high rates of cardiac disease. They stressed caution in interpreting the results, however, because the included trials were designed to analyze the incidence of CIN, not patient outcomes such as death and the need for dialysis. Also, the authors found evidence of publication bias favoring bicarbonate therapy for the prevention of CIN.

More research is needed to determine whether the reduction in CIN translates into long-term benefits, the authors added. Future trials should include patients with and without kidney disease and compare sodium bicarbonate-based regimens with other contrast procedures.

Chlorhexidine-impregnated sponges improve catheter-related infection rates in the ICU

Sponges impregnated with chlorhexidine gluconate improve rates of catheter-related infection in the intensive care unit (ICU), according to a recent study.

Researchers performed a randomized, controlled trial to determine whether applying a chlorhexidine gluconate-impregnated sponge (CHGIS) to intravascular catheter dressings decreased rates of catheter-related infections (CRIs), and whether dressings could be changed every seven days instead of every three days without increasing infection rates. The study involved 1,636 patients cared for at seven ICUs in France. Patients were randomly assigned to one of four treatment groups: CHGIS dressing changed every three days, CHGIS dressing changed every seven days, standard dressing changed every three days, or standard dressing changed every seven days. Outcome measures were major CRIs for type of dressing and colonization rates for duration of dressing changes. The study results appeared in the March 25 Journal of the American Medical Association.

While overall infection rates were low in all groups, patients in the CHGIS dressing group were less likely to develop major CRIs (0.6 per 1,000 catheter-days vs. 1.4 per 1,000 catheter days; hazard ratio, 0.39 [95% CI, 0.17 to 0.93]) and catheter-associated bloodstream infections (0.40 per 1,000 catheter-days vs. 1.3 per 1,000 catheter-days; hazard ratio, 0.24 [95% CI, 0.09 to 0.65]). Eight patients in the CHGIS dressing group developed severe contact dermatitis. Catheter colonization rates were 7.8% (142 of 1,657 catheters) in patients whose dressings were changed every three days and 8.6% (168 of 1,828 catheters) in patients whose dressings were changed every seven days (mean absolute difference, 0.8% [95% CI, −1.78% to 2.15%]).

The authors acknowledged their study's limitations, including its lack of double-blinding and the inherent difficulty of diagnosing major CRIs. However, they concluded that CHGIS dressings reduced infection rates in the ICU by 60% even when infection rates were low, and that changing dressings every seven days rather than every three days appeared to be safe.

An accompanying editorial pointed out the need for a cost-effectiveness analysis that would include adverse events, such as the incidence of contact dermatitis noted by the study authors. However, the editorialists wrote, the current study “has the potential to change the current clinical approach, given that rates of catheter-related bloodstream infection were driven even lower through the relatively simple use of a CHGIS dressing.”