CardioExchange Archive

Allopurinol May Be Beneficial in Stable Angina: In addition to its well established role in treating gout, allopurinol may turn out to have beneficial effects in patients with chronic stable angina, according to a new study published online in the Lancet. In a double-blind, randomized, crossover trial, Awsan Noman and colleagues compared allopurinol with placebo in 65 stable angina patients. From a baseline of 232 s, the median time to ST depression was increased to 298 s with allopurinol and 249 s with placebo. The difference between the groups was highly significant. Compared to placebo, allopurinol also significantly increased median total exercise time and time to chest pain. Allopurinol was well tolerated throughout the trial.

In an accompanying comment, Renjith Antony and Henry Dargie write that the treatment effect of the study drug was similar to other established angina drugs, although it had no effect on hemodynamics. One possible mechanism of action, they say, is that allopurinol may prevent “deleterious effects of oxidative stress on endothelial dysfunction and energy supply.” They conclude: “Although further work is needed to confirm allopurinol’s putative anti-ischaemic effects and to better understand its mechanism of action, allopurinol joins a growing list of compounds that tests the conventional wisdom on what constitutes antianginal therapy. Although prevention of coronary artery disease remains important, protecting the myocyte from ischaemia is a logical and pragmatic approach to a disabling condition for which several mechanisms might be responsible.”

CANOE Paddles Into the Avandia Storm: Rosiglitazone is effective in preventing progression to diabetes, but very public concerns have been raised about its cardiovascular safety. Investigators in Canada sought to assess the efficacy of a low-dose regimen, in the hopes that adverse effects would be reduced. The CANOE (CAnadian Normoglycemia Outcomes Evaluation) trial randomized 207 patients with impaired glucose tolerance to low-dose combination therapy with rosiglitazone and metformin or matching placebo. After 3.9 years, diabetes occurred in 39% of the control group compared with 14% of the combination-therapy group (P<0.0001). In addition, more patients in the treatment group achieved normal glucose tolerance: 80% versus 53% in the placebo group (P=0.0002).

“These results lend support to the notion of use of low-dose combination therapies as an effective means to manage complex metabolic disorders,” the investigators write in their online report in the Lancet. But they acknowledge that the trial “was not designed nor powered to establish long-term effects on cardiovascular safety. CANOE cannot provide additional definitive data for the controversy relating to the specific cardiovascular safety of rosiglitazone.” In an accompanying comment, Thomas Buchanan and Anny Xiang write that “the larger issues that have cast doubt on use of drugs to prevent diabetes are not addressed by the CANOE trial” and that successful prevention of diabetes will require treatments that halt the deterioration of β-cell function.

Ticagrelor NDA Scheduled for July FDA Panel: The FDA Cardiovascular and Renal Drugs Advisory Committee will meet on July 28 to consider the new drug application for ticagrelor (Brilinta, AstraZeneca) “for the proposed indication for use in acute coronary syndrome (including heart attacks and any of a group of signs and symptoms, such as chest pain or shortness of breath, that are consistent with blockages in the blood vessels that supply the heart).” (FDA Meeting Announcement)

Heart Failure Monitoring Finds a CHAMPION: Results of the phase III CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) Trial were presented by William Abraham at the Heart Failure Congress 2010 earlier this week in Berlin, Germany. Some 550 NYHA Class III HF patients were randomized to receive either traditional therapy or the new device, which is about the size of a paper clip and monitors pulmonary artery pressure. At 6 months, there were 83 HF hospitalizations in the device group versus 120 in the control group (31% vs. 44%, P<0.001). “This study represents the first major breakthrough in the management of heart failure in nearly a decade,” said Abraham, in a press release issued by the European Society of Cardiology. “For the first time instead of managing symptoms or weight gain the device allows us to directly manage patient’s pulmonary pressures.”

Oxygen After Cardiac Arrest — More May Not Be Better: Kilgannon and colleagues studied  6,326 patients who had undergone cardiopulmonary resuscitation following cardiac arrest and who were enrolled in the Project IMPACT critical care database. They found that 18% of the population had hyperoxia upon first arterial blood gas determination, and these patients had significantly higher in-hospital mortality (63%) compared to the normoxia group (45%) and the hypoxia group (57%). The study appears in JAMA. In an accompanying editorial, Patrick Kochanek and Hulya Bayir write: “Given the rather conservative definition of hyperoxia (PaO2 ≥300 mm Hg), the true incidence of more moderate levels of hyperoxia is likely to be quite high…. this finding underscores the possibility that further meaningful improvements in outcome might result from careful attention to appropriately titrating basic aspects of extracerebral physiology at the bedside, such as prevention of hyperoxia.”

Shorter Hospital Stays Not Necessarily Better: Shorter hospital stays for heart failure patients have resulted in fewer deaths in the hospital, but at the cost of more readmissions, leading researchers to speculate that “because length of stay has substantially decreased, improvement is less than what might be suggested by in-hospital mortality.” Writing in JAMA, Hector Bueno and colleagues (including senior author Harlan Krumholz, who is the editor-in-chief of CardioExchange) analyzed Medicare data from nearly 7 million heart failure hospitalizations from 1993 until 2006. They conclude that heart failure patients “may benefit from more attention to the care and outcomes in the early transition period after hospital discharge.”

Shorter Delays to Reperfusion Are Better: To assess the impact of time to reperfusion, Laurie Lambert and colleagues analyzed data from nearly all STEMI patients treated in Quebec for 6 months. Of the patients who underwent reperfusion, 78.6% received PCI and 21.4% fibrinolysis. When both treatment groups were combined, treatment beyond the recommended time limit was associated with a significantly higher risk for death at 30 days and a similar trend at 1 year when compared to timely treatment. In their paper in JAMA, the authors write that “at the regional level, after adjustment, each 10 percent increase in patients treated within the recommended time was associated with a decrease in the region-level odds of overall 30-day mortality.” In an accompanying editorial, Deepak Bhatt writes that “barring contraindications, prompt fibrinolysis (and transfer to a PCI center) would be preferred in many patients if the alternative is untimely primary PCI.”

Better Use of Bleeding Avoidance Strategies in PCI: Steven Marso and colleagues analyzed data from 1.5 million PCI patients from hospitals enrolled in the NCDR (National Cardiovascular Data Registry) to examine the use of bleeding avoidance strategies. Manual compression was used in 35% of cases, closure devices in 24%, bivalirudin in 23%, and the combination of a closure device and bivalirudin in 18%. The rate of bleeding was 2.8% for manual compression, 2.1% for closure devices, 1.6% for bivalirudin, and 0.9% for combination therapy. The investigators reported an unusual paradox— patients at high risk for bleeding were less likely to receive combination therapy. In their JAMA paper, they write that their findings “emphasize the opportunity to improve the safety of PCI and to further explore cost efficacy by directing such strategies to those patients most likely to benefit from them.”

Enrollment in Eplerenone Trial Stopped Early: The Data Safety Monitoring Committee has ended enrollment in the EMPHASIS-HF trial after determining that the trial had met its primary efficacy endpoint. According to a press release issued by Pfizer, the trial was testing eplerenone versus placebo in patients with established mild-to-moderate heart failure who were also at risk for sudden death. The primary endpoint was the first occurrence of either cardiovascular death or heart failure hospitalization. It had been anticipated that the trial would last until 2011.

Aspirin Recommended for Primary Prevention in High-Risk Diabetics: In a joint statement from the American College of Cardiology Foundation, the American Diabetes Association, and the American Heart Association, low-dose aspirin is deemed “a reasonable measure” to prevent a first cardiovascular event in diabetics who also have a high risk for heart disease. “Because the relative risk reduction appears to be modest, the panel felt that we are on strongest ground recommending aspirin for those at increased cardiovascular disease (CVD) risk, defined by the age categories and risk factors mentioned or by a calculation of CVD risk,” said the lead author of the statement, Michael Pignone, in an AHA press release.

Transcranial Doppler Stratifies Risk in Asymptomatic Carotid Stenosis: People with asymptomatic carotid stenosis of at least 70% who had embolic signals on transcranial doppler (TCD) were two and a half times more likely to have an ipsilateral stroke or TIA than those without embolic signals, according to results of the Asymptomatic Carotid Emboli Study (ACES) presented at the European Stroke Conference in Barcelona and published online in Lancet Neurology. The authors concluded that “ACES shows that detection of embolic signals by TCD can identify groups of patients with asymptomatic carotid stenosis who are at low or high risk of future stroke. This technique might be a useful risk predictor for identifying those patients who might benefit from intervention with carotid endarterectomy.”