Merck Plugs Arcoxia, Again and Again
3 CommentsBy Ed Silverman // February 8th, 2007 // 6:44 pm
You don’t expect the drugmaker to quit, do you?
Of course not. The latest effort is published in The Lancet, and the Merck-funded study finds the incidence of upper gastrointestinal events in patients on Arcoxia was less than in those folks taking diclofenac. The authors reached their conclusion after analyzing the so-called MEDAL trials. (You can read it here, but registration is required).
That’s good news for Merck, which sells Arcoxia in 62 countries, but must still convince the FDA that its worth sticking out its regulatory neck to approve its newest Cox-2 painkiller. Despite being tarred-and-feathered for its handling of Vioxx, the agency hasn’t ruled out such a move. Merck is working furiously to ensure that it happens.
Ah, but not so fast. An accompanying Lancet editorial points out that, although Arcoxia reduced upper GI events, the upside was actually tiny - to prevent one uncomplicated GI problem, you had to treat 259 patients. Moreover, the alternative may be safer and cheaper - combined usage of a proton-pump inhibitor and an older type of painkiller.
Why safer? Last year, a study showed that diclofenac poses a much greater cardiovascular risk than several similar drugs. Then yet another study found that Arcoxia was no different than diclofenac. Remember that Arcoxia works similarly to Vioxx, which was yanked for causing heart attacks and strokes.
So why do need this drug? And can we count on the FDA to answer that question correctly?
[tags]Arcoxia, FDA, Merck, The Lancet, Vioxx[/tags]
Michal R. Pijak
Aspirin versus acetaminophen: a comparative view.
In his recent article Jacob Karsh(1) indicated that both coxibs and traditional NSAIDs should not be prescribed in patients at higher cardiovascular(CV) risk. He also noted that in many painful conditions treatment with NSAIDs is not necessary or can be substituted for acetaminophen. In my opinion the rational choice for patients with CV and gastrointestinal(GI) risk factors is the use of aspirin combined with a proton-pump inhibitor.
There is good evidence that analgesic doses of aspirin (up to 1500mg) are associated with protection from CV events.(2,3) Furthermore, aspirin dose or its higher lifetime use is not significantly associated with hypertension(4) or renal toxicity.(5,6) Importantly, a recent meta- analysis of 24 randomised controlled trials found no evidence of dose- responsiveness for bleeds over a wide range of doses (50 to 1500 mg/day).(7) Indeed, aspirin in doses commonly used in practice, has an excellent safety profile.(8)
On the contrary, recent evidence suggest that both NSAIDs and acetaminophen can raise cardiovascular risk. (9) High acetaminophen use may also increase the risk of hypertension(4) and a decrease of renal function.(5) Interestingly, increased acetaminophen use has now been linked to increased prevalence of asthma and chronic obstructive pulmonary disease, and with lowered lung function.(10)
Surprisingly, a recent case-control study showed that acetaminophen (>2 g per day) was associated with a greater risk of GI perforation or bleed(11) and one cohort study reported a dose-response relationship between acetaminophen and dyspepsia.(12) It appears that regular use of acetaminophen is also associated with symptoms of severe diverticular disease, particularly bleeding.(13)
Lastly, compelling evidence suggests that aspirin and other NSAIDs are superior to acetaminophen for improving moderate-to-severe pain in patients with osteoarthritis(14,15,16) and rheumatoid arthritis.(17) Likewise, in acute pain states aspirin provides significant and more rapid analgesia than paracetamol.(18)
References
1. Karsh J. Anti-inflammatory drugs: what is safe? CMAJ 2006;175:449.
2. Antithrombotic Trialists’ Collaboration. Collaborative meta- analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
BMJ 2002;324:71-86.
3. Johnson ES, Lanes SF, Wentworth CE 3rd, Satterfield MH, Abebe BL,
Dicker LW.A metaregression analysis of the dose-response effect of aspirin on stroke. Arch Intern Med 1999;159:1248-53.
4. Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 2005;46:500-7.
5. Curhan GC, Knight EL, Rosner B, Hankinson SE, Stampfer MJ. Lifetime nonnarcotic analgesic use and decline in renal function in women. Arch Intern Med 2004;164:1519-24.
6. Dubach UC, Rosner B, Sturmer T. An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987) N Engl J Med 1991;324:155-60.
7. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000;321:1183-7.
8. Fries JF, Ramey DR, Singh G, Morfeld D, Bloch DA, Raynauld JP. A reevaluation of aspirin therapy in rheumatoid arthritis. Arch Intern Med 1993;153:2465-71.
9. Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113:1578-87.
10. McKeever TM, Lewis SA, Smit HA, Burney P, Britton JR, Cassano PA. The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function. Am J Respir Crit Care Med 2005;171:966-71.
11. Garcia Rodriguez LA, Hernandez-Diaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 2001;12:570-6.
12. Rahme E, Pettitt D, LeLorier J. Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population. Arthritis Rheum 2002;46:3046-54.
13. Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Willett WC. Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men. Arch Fam Med 1998;7:255-60.
14. Lee C, Straus WL, Balshaw R, Barlas S, Vogel S, Schnitzer TJ. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta- analysis. Arthritis Rheum 2004;51:746-54.
15. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006;(1):CD004257.
16. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 2004;63:901-7.
17. Wienecke T, Gotzsche PC. Paracetamol versus nonsteroidal anti- inflammatory drugs for rheumatoid arthritis. Cochrane Database Syst Rev 2004;(1):CD003789.
18. Seymour RA, Hawkesford JE, Sykes J, Stillings M, Hill CM. An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery. Br Dent J 2003;194:153-7.
Michal R. Pijak, Assistant Professor and Consultant in Internal Medicine, Rheumatology and Clinical Immunology, Department of Internal Medicine, Slovak Medical University, Bratislava, Slovakia
He knows
Dr. Pijak, is right, of course. However in the real world of Big pharma where profit and shareholders’ value are the king, the benefits to patients are only necessary means to acheive it. There is not much profit in aspirin or any other cheap but effective drug. New ones are needed to be able to charge new and greater prices.
This is where the marketing machines of big pharma come in, that use almost any means of promotion including getting (read buy) some of the top specialists on their side to push it. Evidence based medicine is manipulated by employing the top specialists who would back up the big pharma claims. Of course there are exceptions where the new is better but that is only occasionally.
He knows, wittnessed a clain by Novarti’s top marketer in which he said “we do not have to develop great drugs, even the mediocre drugs if marketed right can become mega-drugs”. Well look at the success of Novartis and thier “competitors” and you can see that his claim was quite right. Apparently thier top gun the doctor is a marketing genious and is surounded by top of the top marketing little geniouses. How can they fail and how can the medical profession resist?
He knows
P.S. It is so gratifying to see someone like Dr. Pijak, from Slovakia where even experts like himself are paid perhaps 1/10th what a similar USA doc would be paid and yet he has resisted the alure of the big pharma corruption. He stays true to his calling. Something thousands of physicians from Basel to New York to Toronto and Montreal especially could learn. We who know them and we who handed out numerous “benefits” on behalf of big pharma we represented, know that ain’t going to happen soon if at all.
Dr. Pijak, and your friends, as the well known song goes ” Don’t go changing just to please…” you know WHO!