No proof of increase heart-related problems associated with rofecoxib- Circulation report shows
November 23, 2001 | 12:00am
An extensive report and analysis which was published recently in the on-line edition of "Circulation," one of the leading and respected journals, showed that there was no significant evidence to prove that the arthritic drug rofecoxib increases the incidence of cardiovascular problems when compared to a placebo (sugar pill) and to traditional non-naproxen non-steroidal anti-inflammatory drugs (NSAIDs).
The investigative report by Dr. Marvin Konstam and colleagues, which was a combined analysis of more than 28,000 patients representing >14,000 patient-years at risk, was derived from 23 various rofecoxib studies that lasted at least 4 weeks dealing with osteoarthritis, rheumatoid arthritis, chronic low back pains and even Alzheimer’s disease.
According to Konstam and colleagues, the outcome measure that was used in their investigation was the combined endpoint defined by the Antiplatelet Trialist’s Collaboration (APTC). The APTC endpoint consists of the combined incidence of cardiovascular (CV), hemorrhagic (heavy bleeding), and unknown death; non-fatal myocardial infarctions (heart attacks); and non-fatal strokes. This endpoint is the most common and widely accepted endpoint in quantifying the overall CV impact of antithrombotic compounds in clinical trials. When rofecoxib was compared to placebo, the results showed a comparable risk of APTC events in both groups. Because placebo was given for a limited duration in the osteoarthritis, rheumatoid arthritis, and chronic low back pain studies, the majority of patient-years came from the Alzheimer’s trials, whose populations included predominantly elderly, male patients. These data reassure that there is no evidence for any increased risk of CV events with rofecoxib.
When rofecoxib was compared to non-naproxen NSAIDs, the results also demonstrated comparable risks of APTC events in both groups. Non-naproxen NSAIDs were only studied in osteoarthritis patients.
The analysis, however, indicated that naproxen was different than other NSAIDs in that it was associated with a decreased risk of CV events compared to rofecoxib. Patient population for the rofecoxib-naproxen analysis was mainly composed of rheumatoid arthritis patients. Although data suggest a possible cardioprotective benefit with naproxen at its standard dose given twice daily (an antiplatelet effect similar to aspirin), no sufficient evidence for such benefit has been established. Patients at risk for CV events who are prescribed a COX-2 inhibitor or an NSAID should continue to receive appropriate antiplatelet therapy as clinically indicated.
The strength of the analyses of Dr. Konstam, et al, was the pooling of individual patient level data from randomized trials that included both rofecoxib and the respective comparators in the same trial. This type of combined analysis with pooled individual data is preferable to comparing absolute rates across different studies, a method used by Mukherjee and colleagues in a recently published article where comparison for CV thrombotic event rates was made between 4 rofecoxib and celecoxib trials and a placebo-group from a meta-analysis of a differently designed trial (aspirin primary prevention trials). That article recently raised the concerns about CV safety profile of COX-2 specific inhibitors.
Konstam and colleagues added that comparing absolute event rates across different studies in a manner adapted by Mukherjee and colleagues is hazardous and considerably less reliable than a prospective, randomized comparison and assumes similar CV risks in the underlying populations, as well as similarity in ascertainment of study endpoints. It would therefore be difficult to draw any conclusions from that article by Murherjee’s group.
In conclusion, the report stated "The analysis provides no evidence for an excess of cardiovascular events for rofecoxib relative to either placebo or the non-naproxen non-steroidal anti-inflammatory drugs (NSAIDs) that were studied. Differences observed between rofecoxib and naproxen are likely the result of the antiplatelet effects of the latter agent."
Circulation is a Houston-based peer-reviewed weekly journal of the AHA intended for cardiologists, cardiovascular surgeons, electrophysiologists, internists, nurses and others interested in cardiovascular medicine. It ranks first in among 63 journals in the Cardiac and Cardiovascular Systems category, first among 60 journals in the Hematology category, and number one among 45 journals in the Peripheral Vascular Disease category.
Rofecoxib, is a COX-2 specific (Cyclooxygenase-2) inhibitor and belongs to a new class of medication known as Coxibs. Rofecoxib is approved by the Bureau of Food and Drugs (BFAD) for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis, the relief of pain and treatment of menstrual pain.
COX-2 specific inhibitors like rofecoxib were designed specifically to treat pain and inflammation while reducing the incidence of gastric irritation and other stomach problems commonly associated with traditional NSAIDs (such as ibuprofen, diclofenac, naproxen, nabumetone, etc). Rofecoxib is not a substitute for aspirin for cardiovascular prophylaxis and does not interfere with the effects of low-dose aspirin on platelets.
It is best to consult a physician for proper diagnosis and the choice of the best treatment option for one’s condition.
The investigative report by Dr. Marvin Konstam and colleagues, which was a combined analysis of more than 28,000 patients representing >14,000 patient-years at risk, was derived from 23 various rofecoxib studies that lasted at least 4 weeks dealing with osteoarthritis, rheumatoid arthritis, chronic low back pains and even Alzheimer’s disease.
According to Konstam and colleagues, the outcome measure that was used in their investigation was the combined endpoint defined by the Antiplatelet Trialist’s Collaboration (APTC). The APTC endpoint consists of the combined incidence of cardiovascular (CV), hemorrhagic (heavy bleeding), and unknown death; non-fatal myocardial infarctions (heart attacks); and non-fatal strokes. This endpoint is the most common and widely accepted endpoint in quantifying the overall CV impact of antithrombotic compounds in clinical trials. When rofecoxib was compared to placebo, the results showed a comparable risk of APTC events in both groups. Because placebo was given for a limited duration in the osteoarthritis, rheumatoid arthritis, and chronic low back pain studies, the majority of patient-years came from the Alzheimer’s trials, whose populations included predominantly elderly, male patients. These data reassure that there is no evidence for any increased risk of CV events with rofecoxib.
When rofecoxib was compared to non-naproxen NSAIDs, the results also demonstrated comparable risks of APTC events in both groups. Non-naproxen NSAIDs were only studied in osteoarthritis patients.
The analysis, however, indicated that naproxen was different than other NSAIDs in that it was associated with a decreased risk of CV events compared to rofecoxib. Patient population for the rofecoxib-naproxen analysis was mainly composed of rheumatoid arthritis patients. Although data suggest a possible cardioprotective benefit with naproxen at its standard dose given twice daily (an antiplatelet effect similar to aspirin), no sufficient evidence for such benefit has been established. Patients at risk for CV events who are prescribed a COX-2 inhibitor or an NSAID should continue to receive appropriate antiplatelet therapy as clinically indicated.
The strength of the analyses of Dr. Konstam, et al, was the pooling of individual patient level data from randomized trials that included both rofecoxib and the respective comparators in the same trial. This type of combined analysis with pooled individual data is preferable to comparing absolute rates across different studies, a method used by Mukherjee and colleagues in a recently published article where comparison for CV thrombotic event rates was made between 4 rofecoxib and celecoxib trials and a placebo-group from a meta-analysis of a differently designed trial (aspirin primary prevention trials). That article recently raised the concerns about CV safety profile of COX-2 specific inhibitors.
Konstam and colleagues added that comparing absolute event rates across different studies in a manner adapted by Mukherjee and colleagues is hazardous and considerably less reliable than a prospective, randomized comparison and assumes similar CV risks in the underlying populations, as well as similarity in ascertainment of study endpoints. It would therefore be difficult to draw any conclusions from that article by Murherjee’s group.
In conclusion, the report stated "The analysis provides no evidence for an excess of cardiovascular events for rofecoxib relative to either placebo or the non-naproxen non-steroidal anti-inflammatory drugs (NSAIDs) that were studied. Differences observed between rofecoxib and naproxen are likely the result of the antiplatelet effects of the latter agent."
Circulation is a Houston-based peer-reviewed weekly journal of the AHA intended for cardiologists, cardiovascular surgeons, electrophysiologists, internists, nurses and others interested in cardiovascular medicine. It ranks first in among 63 journals in the Cardiac and Cardiovascular Systems category, first among 60 journals in the Hematology category, and number one among 45 journals in the Peripheral Vascular Disease category.
Rofecoxib, is a COX-2 specific (Cyclooxygenase-2) inhibitor and belongs to a new class of medication known as Coxibs. Rofecoxib is approved by the Bureau of Food and Drugs (BFAD) for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis, the relief of pain and treatment of menstrual pain.
COX-2 specific inhibitors like rofecoxib were designed specifically to treat pain and inflammation while reducing the incidence of gastric irritation and other stomach problems commonly associated with traditional NSAIDs (such as ibuprofen, diclofenac, naproxen, nabumetone, etc). Rofecoxib is not a substitute for aspirin for cardiovascular prophylaxis and does not interfere with the effects of low-dose aspirin on platelets.
It is best to consult a physician for proper diagnosis and the choice of the best treatment option for one’s condition.
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