Vioxx, NSAIDs linked to higher CHF hospitalization rates

[Guest guest]

Rheumawire

May 28, 2004

Rofecoxib, NSAIDs linked to higher CHF hospitalization rates

London, UK - Results of a new observational study suggest that use of

nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) as well as

the COX-2 inhibitor rofecoxib (Vioxx®, Merck & Co) is associated with a

higher risk of hospital admission for congestive heart failure compared

with controls [1]. No such increase in CHF hospitalization risk was seen

with another COX-2 inhibitor, celecoxib (Celebrex®, Pharmacia & Pfizer),

in this cohort, although all agents were linked to new prescriptions for

antihypertensive or CHF medications.

The study appears in the May 29, 2004 issue of the Lancet.

Despite the observational nature of the study, the researchers, led by

Dr Muhammad Mamdani (Institute for Clinical Evaluative Sciences,

Toronto, ON), conclude, " Our findings suggest significant differences

between nonselective NSAIDs and individual COX-2 inhibitors with respect

to risk of admission for congestive heart failure. The clinical

relevance of these findings, in view of the widespread use of the drugs,

warrants implementation of large-scale randomized controlled trials to

examine this issue further. "

Despite the safety of the new COX-2 inhibitors relative to traditional

NSAIDs such as ibuprofen and naproxen in terms of gastrointestinal

bleeding, concerns have been raised for some time now about the

cardiovascular effects of these agents. A number of reports over the

past few years have linked the use of rofecoxib, particularly at higher

doses, with an increased risk of MI. A recent report by et al,

for example, showed a 24% increased risk for MI with rofecoxib over

celecoxib [2]. However, not all studies have had consistent findings.

For example, a previous observational study by Mamdani and colleaguesthe

same authors of the current paper using the same databasefound no

increase in MI with " commonly used " lower doses of rofecoxib, although

the numbers of patients on high doses of the drug were too small to make

any conclusions about the higher-dose ranges, Mamdani told rheumawire

[3]. The issue is still hotly debated.

Beyond these potential thrombotic effects, however, the use of

traditional NSAIDs has been linked to an increased risk of congestive

heart failure, increased hypertension and edema, and possible adverse

effects on renal function, Mamdani said. In this report, a

population-based, retrospective cohort study, they sought to see what,

if any, similar effects might be associated with the now widely used

COX-2 inhibitors.

Using a healthcare database in Ontario, Canada, they identified

NSAID-naïve individuals who started treatment with rofecoxib (n=14 583),

celecoxib (n=18 908), or a nonselective NSAID (n=5391) and then randomly

selected 100 000 non-NSAID users as controls. They report that relative

to non-NSAID users, patients on rofecoxib and the nonselective NSAIDs

had a higher risk of hospital admission for congestive heart failure

over follow-up than controls, but not those taking celecoxib.

Subgroup analysis showed that those with a history of CHF admission in

the past 3 years were 15 to 30 times more likely to have a new admission

than those who did not have such a history. When patients were then

stratified by history of CHF admission, among those with no previous

history of CHF, rofecoxib users were at significantly increased risk for

a new admission relative to non-NSAID users, while celecoxib and

nonselective NSAID users were not. In those with a history of CHF, both

rofecoxib and nonselective NSAID users were at increased risk for CHF

readmission, while those on celecoxib were not.

However, among patients not previously receiving medications for

hypertension or the treatment of CHF, users of all 3

medicationsrofecoxib, celecoxib, and nonselective NSAIDswere more likely

than non-NSAID users to begin using drugs for hypertension and CHF. This

finding, they write, " suggests a need for careful monitoring of

cardiovascular effects for patients receiving rofecoxib, celecoxib, or

nonselective NSAIDs. "

" I don't want it to seem like celecoxib is a wonder drug without any

side effects; I don't think that's true, " Mamdani told rheumawire.

" The message to physicians is there should be more judicious use of

these drugs, particularly given the associations between them and

elevations in blood pressure and possibly congestive heart failure, "

Mamdani concluded.

However, these agents are effective in managing pain and inflammation,

he added, and patients and physicians will have to balance the risks and

benefits. " If it's something that could be avoided then it's probably

best to avoid it, as with any drug, " he said. If patients are going to

be placed on these drugs, blood pressure should be monitored closely and

risk factors for CHF as well as renal status should be taken into

account, he concluded.

Dr Debabrata Mukherjee (University of Michigan, Ann Arbor), coauthor of

a previous editorial on this subject, told rheumawire this latest study

provides further evidence that selective COX-2 inhibitors may have

detrimental cardiovascular effects.

" The premise of selective coxibs is that they're safer than the

nonsteroidals, but if they're causing more hypertension, potentially

more myocardial infarctions, and more heart failure, obviously it

negates any potential safety benefit, and these drugs remain several

times more expensive than the traditional nonsteroidals, " Mukherjee

said.

Observational studies are flawed, though, and the only way to answer the

question definitively is by randomized prospective studies with

predefined cardiovascular end points, he said. At least 1 such trial is

now ongoing, he noted, with lumiracoxib (Prexige®, Novartis).

Sources

1. Mamdani M, Juurlink DN, Lee DS, et al. Cyclo-oxygenase-2 inhibitors

versus non-selective non-steroidal anti-inflammatory drugs and

congestive heart failure outcomes in elderly patients: a

population-based cohort study. Lancet 2004; 363:1751-1756.

2. DH, Schneeweiss S, Glynn RJ, et al. Relationship between

selective cyclooxygenase-2 inhibitors and acute myocardial infarction in

older adults. Circulation [DOI: 10.1161/01.CIR.0000127578.21885.3E].

2004 Apr 19. Available at: http://circ.ahajournals.org.

3. Mamdani M, Rochon P, Juurlink DN, et al. Effect of selective

cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute

myocardial infarction in the elderly. Arch Intern Med 2003 Feb 24;

163(4):481-6.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[Guest guest]

,

I was on Vioxx for the last few years and have become increasingly concerned

about the safety issues surrounding it.

My BP used to be so low - 100/65 that sometimes I¹d get lightheaded. In the

last few years my pressure went up, but since it was still considered low,

my doctors didn¹t seem to be concerned. Even though I expressed concern to

them, telling them that my pressure was normally very low, so even 120/80 is

high for me. Before I left NJ my RD was considering BP medication. At the

time I attributed high stress as the problem.

Right after moving here I discontinued Vioxx after reading one article to

many about the cardiac implications.

A month later I went to my new GP and low and behold my pressure was back to

100/65. Needless to say I won¹t touch Vioxx even though it does give me

quite a bit of relief. I¹ve been taking as much ibuprofen as I¹m allowed

and hopefully when I get in to my first RD appointment next week, he will

have other ideas.

a

> Rheumawire

> May 28, 2004

>

> Rofecoxib, NSAIDs linked to higher CHF hospitalization rates

>

> London, UK - Results of a new observational study suggest that use of

> nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) as well as

> the COX-2 inhibitor rofecoxib (Vioxx®, Merck & Co) is associated with a

> higher risk of hospital admission for congestive heart failure compared

> with controls [1]. No such increase in CHF hospitalization risk was seen

> with another COX-2 inhibitor, celecoxib (Celebrex®, Pharmacia & Pfizer),

> in this cohort, although all agents were linked to new prescriptions for

> antihypertensive or CHF medications.

>

> The study appears in the May 29, 2004 issue of the Lancet.

>

> Despite the observational nature of the study, the researchers, led by

> Dr Muhammad Mamdani (Institute for Clinical Evaluative Sciences,

> Toronto, ON), conclude, " Our findings suggest significant differences

> between nonselective NSAIDs and individual COX-2 inhibitors with respect

> to risk of admission for congestive heart failure. The clinical

> relevance of these findings, in view of the widespread use of the drugs,

> warrants implementation of large-scale randomized controlled trials to

> examine this issue further. "

>

> Despite the safety of the new COX-2 inhibitors relative to traditional

> NSAIDs such as ibuprofen and naproxen in terms of gastrointestinal

> bleeding, concerns have been raised for some time now about the

> cardiovascular effects of these agents. A number of reports over the

> past few years have linked the use of rofecoxib, particularly at higher

> doses, with an increased risk of MI. A recent report by et al,

> for example, showed a 24% increased risk for MI with rofecoxib over

> celecoxib [2]. However, not all studies have had consistent findings.

> For example, a previous observational study by Mamdani and colleaguesthe

> same authors of the current paper using the same databasefound no

> increase in MI with " commonly used " lower doses of rofecoxib, although

> the numbers of patients on high doses of the drug were too small to make

> any conclusions about the higher-dose ranges, Mamdani told rheumawire

> [3]. The issue is still hotly debated.

>

> Beyond these potential thrombotic effects, however, the use of

> traditional NSAIDs has been linked to an increased risk of congestive

> heart failure, increased hypertension and edema, and possible adverse

> effects on renal function, Mamdani said. In this report, a

> population-based, retrospective cohort study, they sought to see what,

> if any, similar effects might be associated with the now widely used

> COX-2 inhibitors.

>

> Using a healthcare database in Ontario, Canada, they identified

> NSAID-naïve individuals who started treatment with rofecoxib (n=14 583),

> celecoxib (n=18 908), or a nonselective NSAID (n=5391) and then randomly

> selected 100 000 non-NSAID users as controls. They report that relative

> to non-NSAID users, patients on rofecoxib and the nonselective NSAIDs

> had a higher risk of hospital admission for congestive heart failure

> over follow-up than controls, but not those taking celecoxib.

>

> Subgroup analysis showed that those with a history of CHF admission in

> the past 3 years were 15 to 30 times more likely to have a new admission

> than those who did not have such a history. When patients were then

> stratified by history of CHF admission, among those with no previous

> history of CHF, rofecoxib users were at significantly increased risk for

> a new admission relative to non-NSAID users, while celecoxib and

> nonselective NSAID users were not. In those with a history of CHF, both

> rofecoxib and nonselective NSAID users were at increased risk for CHF

> readmission, while those on celecoxib were not.

>

> However, among patients not previously receiving medications for

> hypertension or the treatment of CHF, users of all 3

> medicationsrofecoxib, celecoxib, and nonselective NSAIDswere more likely

> than non-NSAID users to begin using drugs for hypertension and CHF. This

> finding, they write, " suggests a need for careful monitoring of

> cardiovascular effects for patients receiving rofecoxib, celecoxib, or

> nonselective NSAIDs. "

>

> " I don't want it to seem like celecoxib is a wonder drug without any

> side effects; I don't think that's true, " Mamdani told rheumawire.

>

> " The message to physicians is there should be more judicious use of

> these drugs, particularly given the associations between them and

> elevations in blood pressure and possibly congestive heart failure, "

> Mamdani concluded.

>

> However, these agents are effective in managing pain and inflammation,

> he added, and patients and physicians will have to balance the risks and

> benefits. " If it's something that could be avoided then it's probably

> best to avoid it, as with any drug, " he said. If patients are going to

> be placed on these drugs, blood pressure should be monitored closely and

> risk factors for CHF as well as renal status should be taken into

> account, he concluded.

>

> Dr Debabrata Mukherjee (University of Michigan, Ann Arbor), coauthor of

> a previous editorial on this subject, told rheumawire this latest study

> provides further evidence that selective COX-2 inhibitors may have

> detrimental cardiovascular effects.

>

> " The premise of selective coxibs is that they're safer than the

> nonsteroidals, but if they're causing more hypertension, potentially

> more myocardial infarctions, and more heart failure, obviously it

> negates any potential safety benefit, and these drugs remain several

> times more expensive than the traditional nonsteroidals, " Mukherjee

> said.

>

> Observational studies are flawed, though, and the only way to answer the

> question definitively is by randomized prospective studies with

> predefined cardiovascular end points, he said. At least 1 such trial is

> now ongoing, he noted, with lumiracoxib (Prexige®, Novartis).

>

>

>

> Sources

>

> 1. Mamdani M, Juurlink DN, Lee DS, et al. Cyclo-oxygenase-2 inhibitors

> versus non-selective non-steroidal anti-inflammatory drugs and

> congestive heart failure outcomes in elderly patients: a

> population-based cohort study. Lancet 2004; 363:1751-1756.

>

> 2. DH, Schneeweiss S, Glynn RJ, et al. Relationship between

> selective cyclooxygenase-2 inhibitors and acute myocardial infarction in

> older adults. Circulation [DOI: 10.1161/01.CIR.0000127578.21885.3E].

> 2004 Apr 19. Available at: http://circ.ahajournals.org.

>

> 3. Mamdani M, Rochon P, Juurlink DN, et al. Effect of selective

> cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute

> myocardial infarction in the elderly. Arch Intern Med 2003 Feb 24;

> 163(4):481-6.

>

>

>

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

>

>

>