JAMA publica mais dois artigos que mostram o risco do inibidores da Cox-2 e, mesmo de outros anti-inflamatórios. Uma metanálise mostra um dado novo, o risco cardiovascular aumentado para o diclofenaco e ibuprofeno. Salva-se o naproxeno. O resumo do resultado é o seguinte:
Data were combined using a random-effects model. A dose-related risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18).
O destaque principal é para o editorial de David Graham denominado “COX-2 Inhibitors, Other NSAIDs, and Cardiovascular Risk. The Seduction of Common Sense”. Alguns tópicos merecem destaque como:
(1) resumindo (parênteses meus): What does this all mean? First, rofecoxib (Vioxx) increases the risk of acute MI (infarto do miocardio) at low and high doses. This risk begins early in therapy, probably with the first dose. There is no initial 18-month period of immunity from risk. Celecoxib (Celebra) also increases risk at doses higher than 200 mg/d; at lower doses, the potential risk is less clear. Several other NSAIDs increase risk, including the COX-2 selective NSAIDs diclofenac (Voltaren) and meloxicam, and the nonselective NSAID indomethacin (Indocid), and probably ibuprofen (Motrin). Meta-analyses of randomized clinical trials and observational studies agree that naproxen is neutral for MI risk.
(2) sugerindo aos médicos: What should physicians do? For most patients with arthritis or other conditions who require chronic pain relief, naproxen appears to be the safest NSAID choice from a cardiovascular perspective. For patients at high risk of NSAID-related gastrointestinal tract complications, naproxen plus a proton pump inhibitor is less costly and as effective, and probably safer, than low-dose celecoxib.
Em resumo, abandonar qualquer anti-inflamatório não hormonal inibidor da Cox-2, bem como outros como diclofenaco e ibuprofeno, ou seja resta somente naproxeno. No caso de irritação gástrica, associar inibidor de bomba.
O texto completo do editorial e mais dois artigos sobre o tema podem ser acessados sem ônus na página do JAMA para quem se cadastrar.
Comentário: tudo que começa mal e apressado evolui pior ainda, como ocorreu com a aprovação dos inibidores da Cox-2. Metanálise não é o melhor delineamento para verifcar risco, porém o único possível. Resta agora estudar bancos de dados já estruturados com menção ao uso de todos os antiinflamatórios.
4 comentários:
Merck's Vioxx Tied to New Threat;
Heart Risks Start Early in Study
By PETER LOFTUS
September 13, 2006
A study identified kidney-related risks for Merck & Co.'s withdrawn Vioxx painkiller, while another study said the drug's cardiovascular risks began soon after treatment, contradicting the company's claim that the risk increased only after long-term use.
One of these studies also found increased cardiovascular risks for an older painkiller, diclofenac, and suggests the drug's regulatory status should be reviewed. Diclofenac is marketed by Swiss drug company Novartis AG under the brands Cataflam and Voltaren.
Both studies were analyses of previous clinical trials, and were published online yesterday by the Journal of the American Medical Association.
Merck, based in Whitehouse Station, N.J., is in the midst of defending itself against thousands of lawsuits claiming that Vioxx use caused heart attacks and other injuries. Merck withdrew Vioxx from the market in September 2004.
Researchers at Harvard Medical School and Harvard's public-health school, who analyzed the results of 114 clinical trials in which some 116,094 people participated, concluded that Vioxx was associated with increased kidney and arrhythmia risks.
The finding of an arrhythmia risk was significant because the first Vioxx trial last year, which Merck lost, involved a man who took Vioxx and died of arrhythmia. Merck had argued during the trial that Vioxx wasn't linked to arrhythmias.
Merck said the Harvard researchers' analysis "addressed the known renovascular risk associated" with so-called Cox-2 inhibitors. It said that Vioxx's product label included information about the risk of peripheral edema and hypertension in certain people and that those risks were well documented in older pain drugs.
A study by researchers at the University of Newcastle in Australia said elevated cardiovascular risks associated with Vioxx could be observed during the first 30 days of treatment. Merck said previously reported data from clinical trials don't support interpretations that there is an increased cardiovascular thrombotic risk with short-term use of Vioxx.
Regarding the diclofenac findings, Novartis spokesman John Gilardi said: "Our view is that this meta-analysis is incomplete. Other epidemiological data does not indicate an increased cardiovascular risk of diclofenac" compared with other nonsteroidal anti-inflammatory drugs
CHICAGO (Reuters) - Two studies offer more evidence about the dangers of some painkillers, adding kidney problems to heart concerns already raised with the drug once sold as Vioxx, researchers said on Tuesday.
One report from Boston's Brigham and Women's Hospital and Harvard Medical School said an analysis of 114 studies involving more than 116,000 people showed that rofecoxib (the chemical name for Vioxx) "was associated with increased renal and (heart) arrhythmia risks."
Why the drug would cause kidney damage is unclear, it added.
Merck & Co Inc. withdrew Vioxx from the market in September 2004 after a three-year study showed it doubled the risk of heart attack and strokes in patients taking it for at least 18 months.
A second report from the University of Newcastle, New South Wales, Australia, said a look at 23 studies confirms findings of an increased risk of heart problems with Vioxx that could be found "during the first 30 days of treatment. This conclusion is consistent with a recent reanalysis ... which contradicts the original suggestion that the vascular risk was only seen after 18 months."
The studies were published in this week's Journal of the American Medical Association (JAMA) along with an editorial from David Graham, a physician who works for the U.S. Food and Drug Administration but whose comments were labeled as his own views and not those of the regulatory agency.
Merck is facing more than 11,500 product liability lawsuits from people claiming to have been harmed by Vioxx.
"What the studies are going to do is provide substantial support for the opinions being expressed by the plaintiffs' experts, and that will serve to increase their credibility and persuasiveness to juries," said Frank McClellan, professor at Temple University's Beasley School of Law.
"Those studies will also be used to cross-examine and impeach Merck's experts who testify that there is no link between the drug and the injuries," McClellan said. "The impact could be profound in the outcomes of the trials."
Merck said it still believes the data confirm the increased heart risk begins only after the medicine had been taken for 18 months.
Merck said in a statement the observations in the JAMA articles and opinions expressed in an accompanying editorial regarding potential increased risks with short-term Vioxx use "are not supported by the current weight of clinical data."
The Australian analysis also found that celecoxib -- sold as Celebrex by Pfizer Inc. -- was not associated with heart problems at a dose no greater than 200 milligrams a day.
It said that its review "raises serious questions about the safety of diclofenac, an older (analgesic) drug" which is sold more in Europe than the United States.
"In conclusion ... diclofenac seems to share this risk and, unlike celecoxib, it appears to be harmful at commonly used doses. We believe there are grounds for reviewing its regulatory status," the report added.
In his editorial, Graham said the studies demonstrate that Vioxx "increases the risk of acute myocardial infarction at low and high doses" and that "there is no initial 18-month period of immunity from risk."
He said Celebrex increases heart risk at doses higher than 200 milligrams per day and several other non-steroidal anti-inflammatory drugs (NSAIDs) increase risk, including diclofenac, meloxicam, indomethacin and "probably" ibuprofen, while studies agree naproxen is "neutral" for heart attack risk.
Graham added that for most patients with arthritis or other conditions requiring chronic pain relief "naproxen appears to be the safest NSAID choice from a cardiovascular perspective." Naproxen is commonly sold as Aleve by Bayer Corp..
(Additional reporting by Bill Berkrot in New York)
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Essa foi a nota da Novartis. Felizmente, a empresa está se defendendo e, não as sociedades médicas fazendo papel de advogado de laboratório.
Fabricante do Cataflam diz, em nota, que estudo é inconclusivo
da Folha Online
A Novartis, laboratório que fabrica o Cataflam e Voltaren, cujo princípio ativo é o diclofenaco, afirma em nota oficial que os estudos sobre os riscos cardiovasculares da substância são inconclusivos.
Uma pesquisa divulgada nesta terça-feira pelo "Journal of the American Medical Association" concluiu que a droga aumenta em 40% as chances de um indivíduo ter uma ataque cardíaco.
Segundo a empresa, "a análise não é aceita pelos órgãos reguladores como evidência clínica para suporte de registro de produtos."
O comunicado diz ainda que outros estudos realizados comparando o diclofenaco a outros antiinflamatórios, como naproxeno, ibuprofeno e os inibidores da COX-2 não chegaram a esse resultado.
"Tais estudos científicos, com evidência médica comprovada, não indicam qualquer aumento do risco cardiovascular relacionado ao uso do diclofenaco em comparação a esses antiinflamatórios," diz a nota. A empresa também divulgou que não pretende retirar os remédios de circulação.
Paulo,
como fica a Nimesulida (Scaflan) nessa história toda?
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