Certo che per essere una molecola morta e sepolta la comunità scientifica ne parla un
pò troppo!!!!!!!!!!!!!!!!!!!!!!!
News NICOX - March 12, 2011
Hier à 01:01
No BP Hike Seen With Novel Anti-Inflammatory
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: March 12, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. Earn CME/CE credit
for reading medical news
Action Points
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■Point out that NSAIDs are often associated with mild increases in systolic blood pressure, particularly in patients treated with antihypertensive therapy.
■Note that, in this study, naproxcinod, an investigational nitric oxide-donating cyclooxygenase inhibitor, had effects on BP similar to that of placebo in patients with OA and less than that seen with naproxen.
The investigational anti-inflammatory naproxcinod may eliminate the blood pressure elevations common with nonsteroidal anti-inflammatory drugs used in osteoarthritis, a pooled safety analysis suggested.
Naproxcinod -- which breaks down into the NSAID naproxen and a nitric oxide donor -- was no different than placebo in its effect on systolic blood pressure in osteoarthritis patients (mean change -0.4 mm Hg from baseline versus placebo, 95% CI -1.6 to 0.8), William B. White, MD, of the University of Connecticut in Farmington, and colleagues found.
By comparison, an equivalent dose of naproxen alone raised systolic pressure by an average 1.4 mm Hg more than placebo over baseline (P=0.032), the group reported online in the American Journal of Cardiology.
Small blood pressure effects can have an important role in cardiovascular risk, they noted in their integrated analysis of the three naproxcinod pivotal trials.
But the evidence for a blood pressure differential with naproxcinod wasn't convincing enough for the FDA, which sided with its advisory panel last year in turning down the novel anti-inflammatory for treatment of osteoarthritis pending further efficacy and safety data.
The drug is the first in a new class of cyclooxygenase (COX)-inhibitors that donates nitric oxide, which White's group suggested made the difference for blood pressure.
"The exogenous release of nitric oxide would be expected to reduce vascular smooth muscle contractility, leading to a reduction in systemic vascular resistance and blood pressure," they explained in the paper.
This property of naproxcinod could provide an effective mechanism to counter the anti-prostacyclin effects typically seen with the traditional NSAIDs," they added.
The group pooled safety data from the three pivotal phase III trials done with naproxcinod in osteoarthritis (two in knee OA, one in hip OA).
The 2,734 patients included were chronic NSAID or acetaminophen users and had been randomized to naproxcinod at 375 mg or 750 mg twice daily; naproxen at 500 mg, equipotent to the 750 mg dose of naproxcinod; or placebo.
Seated office blood pressure measured at 13 weeks of double-blind treatment across the studies fell from baseline with naproxcinod and placebo and remained stable with naproxen.
Mean change from baseline was not statistically different from placebo for systolic pressure with either naproxcinod dose and significantly lower than naproxen at the higher naproxcinod dose (-1.8 mm Hg, P≤0.03), though not at the lower dose (-0.7 mm Hg, 95% CI -2.2 to 0.7).
For diastolic pressure, both naproxcinod doses came out below naproxen for change from baseline (P<0.05).
The researchers also looked at use of renin-angiotensin system inhibitors among the 44% of participants with hypertension under treatment with antihypertensive medication (27.7% were on single-agent RAS inhibition).
Previous studies had suggested that NSAIDs are more likely to destabilize blood pressure control when patients are taking these classes of antihypertensives, the researchers noted.
In the pooled pivotal trial data among patients on a RAS inhibitor as the sole antihypertensive, naproxcinod resulted in no significant change from baseline in blood pressure compared with placebo (mean difference 1.0 mm Hg with 750 mg, 95% CI -2.4 to 4.3, and 0.4 mm Hg with 375 mg, 95% CI -4.4 to 5.1), whereas naproxen did (mean difference 5.3 mm Hg, P=0.016).
The pattern was similar in patients on RAS inhibitor-diuretic combinations, but other regimens weren't common enough to analyze.
Serious adverse cardiovascular events were uncommon at 0.3% to 0.6% across the groups, with placebo having the highest rate among them.
How these pooled data might play into naproxcinod's future remain unclear, but drug developer NicOx has said it is planning to appeal the FDA's decision to turn down the novel anti-inflammatory through a formal dispute resolution process in the first quarter of this year.
A decision on the drug from European regulators is expected this summer.
.........A parte gli scherzi...non ci si aspetta nulla da questo ricorso...è stato fatto come atto duvuto ma contro la FDA nulla può Nicox.....occorrerebbe un miracolo, per chi ci crede ( ai miracoli) !!!
