The US Food and Drug Administration (FDA) has recently approved an expanded indication for olmesartan medoxomil for the treatment of hypertension in pediatric patients aged 6 to16 years. The angiotensin II receptor blocker previously was reserved for use in adults.

The prevalence of pediatric hypertension has been increasing since the late 1980s, in parallel with increases in children's weight. Treatment is important because the condition represents an independent risk factor for adult hypertension and is associated with early markers of cardiovascular disease.

The approval was based on data from a randomized, double-blind study of pediatric patients (n = 302; 112 black and 190 mixed racial heritage) with hypertension of predominantly essential origin. Patients who weighed from 20 to less than 35 kg were randomly assigned to receive 2.5 or 20 mg of olmesartan once daily; those who weighed 35 kg or more were randomly assigned to a daily dose of 5 or 40 mg. After 3 weeks, patients were reassigned to continued olmesartan therapy or placebo.

Results of the initial dose-response phase showed that olmesartan significantly reduced both systolic and diastolic blood pressure in a weight-adjusted dose-dependent manner. Overall, the 2 dose levels of olmesartan (low and high) significantly reduced systolic blood pressure by 6.6 and 11.9 mm Hg from the baseline, respectively. These reductions in systolic blood pressure included both drug and placebo effect.

During the randomized withdrawal to placebo phase, mean systolic and diastolic blood pressure at trough were significantly lower in patients continuing olmesartan therapy than in those withdrawn to placebo (Δ, 3.2 mm Hg and 2.8 mm Hg, respectively). As observed in adult populations, blood pressure reductions were smaller in black patients.

Pediatric use of olmesartan was well-tolerated; adverse events were similar to those reported in adult studies, with dizziness most commonly reported (incidence, 3%).

Pediatric dosing of olmesartan is based on body weight. The recommended starting and maintenance doses for patients weighing from 20 to less than 35 kg are 10 mg and 20 mg once daily, respectively; patients weighing 35 kg or greater should receive an adult starting dose of 20 mg once daily and be maintained at a daily dose of 20 to 40 mg. An extemporaneous suspension may be prepared for children unable to swallow tablets.

Adapted from: Drugs.com. Last accessed on 15/02/2010

Further results from the SPARCL trial show that stroke patients given atorvastatin have a reduced risk for coronary heart disease (CHD) events, as well as recurrent stroke.

The 4731 patients recruited to the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial were free of known CHD at baseline, so any that manifested during the 4.9-year follow-up represented a first event.

It is notable that the relative reduction in the risk for major coronary events in SPARCL patients was double that of stroke events, said researchers.

During follow-up, 5.1% of patients randomly assigned to placebo suffered a major coronary event and 8.6% suffered any CHD event (coronary events plus revascularization, unstable angina, or angina/ischemia requiring hospitalization). In patients taking atorvastatin 80 mg/day, the corresponding rates were 3.4% and 5.2%.

Thus, the risk for major coronary events was reduced by 35% among patients taking atorvastatin and the risk for CHD was reduced by 42%, after accounting for time since entry event, age, and gender.

The risk reductions, while not significant in all subgroups, did not appear to be influenced by whether patients had large-vessel or small-vessel disease.

Results of this trial, as well as data from long-term observational studies and other clinical trials, show that the risk for myocardial infarction is far from negligible and eventually equals or exceeds the risk for recurrent stroke, said researchers.

New observations from a group of US doctors suggested a possible link between the H1N1 influenza A infection and fulminant myocarditis. Within a recent 30-day period, the group documented four cases of fulminant myocarditis, an atypical number compared with their usual experiences.

The findings raise the possibility that the novel H1N1 influenza A virus is more commonly associated with a severe form of myocarditis than previously encountered influenza strains, according to the lead author.

The clinicians, from Rady Children's Hospital in San Diego, wrote that their tertiary-care hospital serves a region that includes approximately 800 000 children, and in the past three years there has been an annual average of just two cases of acute myocarditis believed to be caused by a virus.

In October 2009, 80 children were admitted with H1N1 influenza A infection. Among these, there were four influenza-associated myocarditis cases, with three children presenting with fulminant myocarditis and one with a fatal outcome. For documentation, two children had elevated cardiac enzymes, three had a significant acute decrease in left ventricular systolic function as shown on the echocardiogram, and one child had histologic evidence of severe myocarditis.

"Our observations warrant a high index of suspicion for myocarditis in children with H1N1 influenza A infection," wrote authors. "Early detection and aggressive management are paramount. Timely intervention with circulatory support may decrease morbidity and mortality, with the potential for a favorable cardiac prognosis."

Fulminant myocarditis caused by a viral infection is uncommon, and influenza-A-virus-associated fulminant myocarditis is "exceedingly rare, with only a few cases reported in the literature," the group pointed out. The exact prevalence is not known because comprehensive screening does not exist. Patients with fulminant myocarditis can present with fatal arrhythmias, atrioventricular block, and/or varying degrees of cardiogenic shock, the clinicians note.

Tapering off clopidogrel treatment after the implantation of a drug-eluting stent (DES) does not result in values of platelet aggregation that are lower than those seen when the antiplatelet medication is abruptly stopped, according to a new study.

The course of platelet-aggregation values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets after discontinuation of clopidogrel, wrote researchers.

In ACS patients who undergo PCI, as well as those treated medically, thrombotic events clustered in the first few weeks after stopping clopidogrel treatment have been reported, suggesting the possibility of a "rebound phenomenon" with blood platelets. Researchers pointed out that the rebound effect has not been studied in a randomized clinical trial.

In this study, 69 patients receiving clopidogrel prior to DES implantation were randomized to a prespecified tapering regimen for four weeks or to abrupt discontinuation. However, the researchers did not observe any difference between the two study arms in platelet-aggregation values measured at two and eight weeks by light transmission aggregometry or multiple electrode aggregometry.

The group noted that regardless of the test used to assess platelet aggregation and the agonist or agonist concentration used for platelet-aggregation measurements, there was no evidence of a rebound phenomenon among those who stopped clopidogrel abruptly.

Although tapering of clopidogrel treatment does not result in significantly lower absolute values of ADP-induced platelet aggregation in the weeks after stopping clopidogrel, a possible clinical benefit of tapering clopidogrel in coronary artery disease patients with prior stent placement cannot be excluded from the results of the present study, they added.

An ongoing study, Abrupt versus Tapered Interruption of Chronic Clopidogrel Therapy after Drug-Eluting Stent Implantation (ISAR-CAUTION), is currently recruiting patients. Also under way is the large, 20 000-patient Dual Antiplatelet Therapy (DAPT) study, which is testing the optimal duration of dual antiplatelet therapies.

Women are more likely than men to have exclusively noncalcified coronary plaques and are less likely than men to have calcified or mixed-composition plaques, which may in part explain why women are at lower risk of cardiac events, according to the authors of a new multidetector computed tomographic (CT) angiography study.

A 416-patient study demonstrated that women have a lower calcified and mixed plaque burden, but no differences in noncalcified plaque compared with men across all age groups. Furthermore, despite the similar overall noncalcified plaque burden, women had a greater proportion of noncalcified plaques to total plaques.

The burden of plaque in women with nonobstructive CAD has tremendous implications for treatment. It also may signify cardiac event risk where other tests may not identify this risk, told study coauthor.It is important to note that all of these markers are uniquely contributed by CT, and given the notable limitations of stress testing in women, these results can have a lot of important implications for improved detection of at-risk women, he added.

One possible explanation of this difference is that estrogen may influence the underlying lipid metabolism and endothelial function and thereby affect plaque development, but further studies are needed to identify the cause of this gender difference in plaque composition, explained authors.

The study evaluated 148 women and 268 men (average age 61) who were symptomatic for coronary disease with multidetector CT angiography. Stenosis of >70% in at least one coronary segment appeared in 11% of the women compared with 25% of men (p<0.0001), and women presented with a significantly lower average number of segments containing calcified plaque (1.43 vs 2.25; p=0.004) and mixed-composition plaques (1.67 vs 2.25; p=0.05). However, there was no statistically significant difference in the average number of noncalcified plaques (0.72 vs 0.86; p=0.21). A greater proportion of the plaques in women were noncalcified (40% vs 28%) than in men, and a lower proportion of plaques were calcified (38% vs 43%; p<0.001) or mixed (23% vs 28%; p<0.001) in women than in men. The same differences were seen in all age groups.

Multivariate-adjusted analysis accounting for age and coronary heart disease risk factors showed that women had 0.38 times the chance of men of having a highly calcified plaque in at least three coronary segments. The odds ratio for a mixed plaque burden in at least three vessels was 0.35. Women in the study had a 19% greater relative distribution of plaque that was noncalcified, and the relative plaque burden was significantly less likely to be calcified or mixed in women than it was in men.

The researchers observed in the study that men, who are more likely to experience an acute cardiovascular event, had a greater proportion and burden of mixed plaques compared with women. This strengthened the notion that mixed plaques might be more likely to be associated with an increased risk of cardiovascular events.

Well-designed, prospective studies are needed to establish the predictive value of each specific plaque subtype, especially whether multidetector CT angiography can further refine risk stratification beyond the determination of global plaque burden, the authors concluded. Also, future studies should also assess differences in plaque composition across different racial groups.

Triple antiplatelet therapy is more effective than dual therapy at reducing ischemic events after implantation of a drug-eluting stent (DES), according to an observational study.

The oral antiplatelet agent cilostazol, adds to the effects of aspirin and clopidogrel against platelet activation, the authors noted. In earlier studies, the drug reduced rates of restenosis and revascularization in patients with DES.

In the current analysis, researchers compared the long-term effectiveness and safety of a triple-drug regimen and a dual-drug regimen after successful implantation of a sirolimus- or paclitaxel-eluting stent.

Out of 3099 patients treated at their institution, 1443 had received triple therapy: aspirin 200 mg/day, clopidogrel (300-mg loading dose, then 75 mg/day), and cilostazol (200-mg loading dose, then 100 mg twice daily). The other 1646 patients received only aspirin and clopidogrel.

Aspirin was administered indefinitely, clopidogrel for at least 6 months, and cilostazol for at least 4 weeks. Follow-up lasted for 12 months.

In the triple therapy group, 5 patients had myocardial infarctions (MI), 2 had stent thrombosis, and 21 died. In the double-therapy group, 15 had MIs, 12 had stent thromboses, and 26 died.

After adjustment, 12-month mortality did not differ between the groups. However, the triple-antiplatelet therapy was associated with significantly lower 12-month risks of MI (hazard ratio 0.233, p = 0.0097) and stent thrombosis (HR 0.136, p = 0.0036). Incidence curves for both stent thrombosis and MI diverged and reached statistical significance at 2 months, after which the curves were parallel.

Rates of major and minor bleeding were similar in the two groups.

In addition to its antiplatelet effect, cilostazol may have several favorable effects on the vascular bed, such as inhibition of atheroma plaque formation, atheroma regression, vasodilatation and favorable change of lipid profile, concluded researchers. Prolonged use of triple antiplatelet therapy may reduce 12-month risks of stent thrombosis and MI after DES implantation, they added.