Continuation of beta-blocker therapy among patients hospitalized for decompensated heart failure is associated with markedly better outcomes compared to heart failure patients in whom beta-blocker therapy is stopped or never started, reported researchers.

Dr. Fonarow of the University of California - Los Angeles Medical Center and colleagues determined the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in 5,791 patients hospitalized with systolic heart failure in a registry with pre-specified 60- to 90-day follow-up at 91 US academic and community hospitals.

Among 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers prior to admission and continued on therapy, 632 (26.6%) newly started on beta-blocker therapy, 79 (3.3%) in whom therapy was withdrawn, and 303 (12.8%) eligible for beta-blocker therapy who did not receive it.

Results of the study showed that the most important therapeutic strategy influencing whether a patient hospitalized with heart failure will survive the next 60 to 90 days was continuing or newly starting beta-blocker medications during hospitalization, said Dr. Fonarow.

Specifically, continuation of beta-blocker therapy was associated with a significantly lower risk of post-discharge death by 40% and death/rehospitalization by 31%, compared with no beta-blocker therapy.

In contrast, discontinuation of beta-blocker therapy on hospital admission was associated with 2.3-fold higher adjusted risk for death compared with continuation of beta-blocker therapy and with similar risk as heart failure patients eligible but not treated with beta-blockers.

Dr. Fonarow concluded that patients who are hospitalized for heart failure and have been taking beta-blockers should be kept on this medication while in the hospital, and if they weren't taking beta blockers already, patients should be started on this medication before they are discharged.

Source: J Am Coll Cardiol 2008; 52:190-199.

Results of a new study have shown that current smokers have increased platelet inhibition and lower platelet aggregation on clopidogrel than nonsmokers. The authors say that the mechanism of this smoking effect deserves further study and may be an important cause of response variability to clopidogrel therapy.

The study was conducted by a group led by Dr Kevin Bliden ( Sinai Center for Thrombosis Research, Baltimore).

Certain studies done earlier had shown similar results. CREDO [Clopidogrel for the Reduction of Events During Observation] study suggested that smoking appeared to influence the clinical effect of clopidogrel with a larger reduction in clinical events seen with the drug in smokers than in nonsmokers. Analysis of the CLARITY [PCI-Clopidogrel as Adjunctive Reperfusion Therapy] trial showing a similar observation.

Dr Kevin Bliden said that smoking has also been shown to induce the cytochrome P1A2 (CYP1A2) enzyme, which converts clopidogrel to its active metabolite.

Researchers analyzed platelet-function data in 259 patients (104 smokers and 155 nonsmokers) undergoing elective percutaneous coronary intervention (PCI) treated with clopidogrel consecutively enrolled in clinical trials at their hospital. Previous smokers were excluded. Of the patients included, 120 were on chronic clopidogrel therapy and were not loaded and 139 were clopidogrel naive and were loaded with 600 mg. Adenosine diphosphate (ADP)-stimulated platelet aggregation was assessed by conventional aggregometry and the ADP-stimulated total and active glycoprotein (GP) IIb/IIIa expression were assessed with flow cytometry.

Results showed that smokers on chronic clopidogrel therapy displayed significantly lower platelet aggregation and ADP-stimulated active GP IIb/IIIa expression compared with nonsmokers (p<0.0008 for both). Similarly, current smokers treated with 600 mg of clopidogrel displayed greater platelet inhibition and lower active GP IIb/IIIa expression compared with nonsmokers (p<0.05). In a multivariate Cox regression analysis, current smoking was an independent predictor of low platelet aggregation (p=0.0001).

Although there have already been some data suggesting that smoking may affect the response to clopidogrel, this study showed that this can be translated into an antiplatelet effect. Noting that clopidogrel has to be activated by cytochrome P450 enzymes, which produce the active metabolite, and that smoking induces one of these enzymes, Gurbel added: "We think that smoking upregulates this pathway." He noted that many other agents that can modulate P450 activity may have an effect on the amount of clopidogrel active metabolite produced. These include Saint John's wort, which also upregulates the pathway, and omeprazole, which competes for the site on the P450 enzymes and therefore slows production of the clopidogrel active metabolite.

Gurbel said that it is not possible to make any clinical recommendations on altering the dose of clopidogrel in smokers or nonsmokers on the basis of these data because this trial was not a prospective study and further studies are required.The effect of smoking will probably not be a simple formula, as its influence will differ from one individual to another.

Source: J Am Coll Cardiol . 2008; 52:531-533.

Antiretroviral drugs for HIV infection do not increase the risk of coronary atherosclerosis, contrary to the findings of some previous studies, a new report by Dr Lawrence A Kingsley ( University of Pittsburgh , PA ) and colleagues revealed.

In a cohort of both HIV-positive--most of who were taking antiretroviral therapy--and HIV-negative men, the researchers found a very similar prevalence of coronary artery calcium (CAC) across the board. And among those who did have CAC, those on highly active antiretroviral therapy (HAART) the longest had the least CAC. There was no evidence at all from this study that being HIV positive or the duration of HAART therapy has anything to do with CAC.

In the present study, researchers measured levels of CAC between 2004 and 2006 in nearly 950 HIV-positive and HIV-negative men participating in the prospective Multicenter AIDS Cohort Study (MACS).

High proportion of individuals included in the study was taking lipid-lowering therapy (around 40% of the study cohort).

Overall, the prevalence of any CAC was not significantly different between any of the groups.

Age-Adjusted Presence of Coronary Calcification, According to HIV and HAART Status of Population

Age-Adjusted Calcification Scores Among Those With Calcification According to HIV and HAART Status of Population

"These results could be due, in part, to lower lipid values of HIV-infected men prior to beginning antiretroviral therapy and high use of lipid-lowering drugs. The key is that controlling risk factors for atherosclerosis should be a priority," Kuller said.

Researchers said that the key message to doctors is that these people have the same risk factors as everybody else and probably should be treated in exactly the same way.

Kuller said that it was still possible that HAART might have a differential effect on clotting and thrombosis, something they are looking at in the SMART study.

Source: AIDS 2008; 22: 1589-1599.

The US Food and Drug Administration (FDA) has issued an alert notifying of the risk for rhabdomyolysis when simvastatin is combined with amiodarone.

The hazard was added to product labeling on simvastatin in 2002, but the FDA said that it continues to receive reports of rhabdomyolysis in patients treated concurrently with the two drugs.

The risk increases particularly when doses of simvastatin greater than 20 mg per day are taken.

Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone, the FDA alert stated.

The alert said that physicians prescribing either simvastatin or simvastatin-containing medications should be aware of the risk and that patients should be advised of the risk and told to report promptly any unexplained muscle pain, tenderness, or weakness.

The FDA reminds physicians that, while the precise mechanism is unknown, the increased risk for rhabdomyolysis is related to amiodarone inhibiting the cytochrome P450 3A4 enzyme that metabolizes simvastatin.

Prescribers should consider use of another statin for patients taking amiodarone, or initiating amiodarone therapy, who require simvastatin doses greater than 20 mg daily to meet their lipid goals, it stated.

Source: US Food and Drug Administration 2008

The American Heart Association has published a scientific statement recommending ambulatory blood pressure monitoring (ABPM) in children and adolescents to help diagnose and manage hypertension.

Clinical hypertension can be identified in children and adolescents and is associated with organ damage even at young ages, said chair of the statement writing group Elaine Urbina (Cincinnati Children's Hospital Medical Center , Ohio , USA ). Accurate diagnosis and early treatment is essential. There is now sufficient experience with ABPM to recommend its use in pediatric patients to assist in diagnosing hypertension, she added.

The statement is expert-opinion driven rather than evidence based because of the lack of data relating ABPM in this age group to hard outcomes. It provided a summary of the current literature and offered guidance on performing ABPM and interpreting results.

The statement indicated that ABPM can be used to distinguish between white coat and true hypertension, detect masked hypertension, evaluate the effectiveness of antihypertensive treatment, and assess BP variability - in particular the dipping status in patients at high risk for end-organ damage, and the severity and persistence of BP elevation.

Ambulatory monitoring is likely to be most useful in children whose office BP readings are up to 10% over the highest acceptable reading, as children with very high readings (more than 10% higher than the highest reading) were more likely to have true high BP, said authors.

These guidelines help pediatric healthcare providers to understand the use of ABPM in monitoring children's BP. A standard technique advocated by a national organization like the AHA is reassuring to parents who want to be sure that their children are receiving consistent, high-quality care.

Source: Hypertension 2008; Advance online publication