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《英国医生杂志》
Clopidogrel helps reduce ischaemic complications in acute MI
Aspirin and fibrinolytic therapy were established as an effective intervention in acute myocardial infarction more than a decade ago, although reperfusion fails to occur in about 20% of treated patients. Improvements have been slow in coming. Antiplatelet therapy with glycoprotein IIb/IIIa inhibitors improved rates of reperfusion and reduced reinfarction but at the unacceptable cost of doubling major bleeds. Now a randomised trial of 3491 patients, all 75 years and under, with ST elevation myocardial infarction finds that the addition of clopidogrel to a standard fibrinolytic regimen improves the patency rate of the artery whose occlusion caused the infarct and reduces ischaemic complications without an increase in adverse events.
Credit: MEDICINE OF JOURNAL ENGLAND NEW
The primary endpoint was a composite of occlusion of the relevant artery at angiography, 4-8 days later, or death or further infarction before angiography. It occurred in 21.7% of the placebo group but only 15% of the group taking clopidogrel. No follow-up beyond 30 days is reported, but since many studies have shown that short term angiographic findings after myocardial infarction predict prognosis, it seems likely that this simple extra intervention will result in long term benefit.
New England Journal of Medicine 2005;352: 1179-89
Celecoxib and non-selective NSAIDs don't increase the risk of myocardial infarction
Last year, as everyone must know by now, the cyclooxygenase-2 (COX-2) selective inhibitor rofecoxib was withdrawn because of worries about its cardiac safety. The question, of course, is whether these doubts also extend to other COX-2 selective inhibitors and to non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Probably not, is the answer, according to a study from Quebec.
Using health insurance and vital statistics databases, the investigators nested a case-control study within a cohort of 113 927 people without a history of myocardial infarction who had been prescribed an NSAID between January 1999 and June 2002. During a mean follow-up of 2.4 years, 2844 people from the cohort were hospitalised for myocardial infarction. Current users of rofecoxib were at increased risk of myocardial infarction (relative risk 1.24, 95% CI 1.05 to 1.46) compared with those who had not used an NSAID in the previous year. In contrast, there was little to suggest any increased risk in current users of celecoxib (0.99, 0.85 to 1.16), although few were taking more than 200 mg a day. The study turned out to have too little statistical power to exclude meaningful differences in risk associated with traditional NSAIDs (1.00, 0.73 to 1.37), naproxen (1.17, 0.75 to 1.84), or meloxicam (1.06, 0.49 to 2.30).
The researchers reckon that their results provide evidence against a broad class effect for COX-2 inhibitor mediated cardiotoxicity. Even so, they advise that new agents with COX-2 inhibitory potency similar to or greater than that of refecoxib should be used only with extreme caution.
Annals of Internal Medicine 2005 April 5 (www.annals.org/cgi/content/full/0000605-200504050-00113v1)
Morphine plus gabapentin is effective for neuropathic pain
Neuropathic pain is a miserable condition interfering with sleep, work, and the enjoyment of life in general. It's a common complication of diabetes, herpes zoster, and several other conditions that cause nerve damage. A wide range of drugs (including anticonvulsants, antidepressants, and analgesics) is used in its management, but it's often not very responsive to treatment. Although trials have shown that several drugs produce modest benefit, patients often find that doses high enough to be effective produce intolerable adverse effects.
The combination of gabapentin and morphine (given orally in a sustained release formulation) seems to be better than either of these drugs given as a single agent. Fifty seven patients with either diabetic neuropathy or postherpetic neuralgia took part in a crossover trial in which they received placebo, morphine, gabapentin, or a combination of gabapentin and morphine in random order during successive five week periods. Pain scores were lowest during treatment with the gabapentin-morphine combination. This treatment was also associated with less pain-related interference with mood and with higher scores for vitality and social functioning, but at the maximum tolerated dose the combination caused a higher frequency of constipation than gabapentin alone and a higher frequency of dry mouth than morphine alone.
Credit: MEDICINE OF JOURNAL ENGLAND NEW
The trial used an active placebo to minimise inadvertent unblinding. Only a quarter of the participants correctly identified when they were receiving the gabapentin-morphine combination, which is no more than would be expected by chance.
It's not clear whether gabapentin and morphine act synergistically or even additively to produce this analgesic effect. But, as the authors argue, a combination with less than additive effects may be clinically useful provided that the adverse effects show even less additivity.
Aspirin and fibrinolytic therapy were established as an effective intervention in acute myocardial infarction more than a decade ago, although reperfusion fails to occur in about 20% of treated patients. Improvements have been slow in coming. Antiplatelet therapy with glycoprotein IIb/IIIa inhibitors improved rates of reperfusion and reduced reinfarction but at the unacceptable cost of doubling major bleeds. Now a randomised trial of 3491 patients, all 75 years and under, with ST elevation myocardial infarction finds that the addition of clopidogrel to a standard fibrinolytic regimen improves the patency rate of the artery whose occlusion caused the infarct and reduces ischaemic complications without an increase in adverse events.
Credit: MEDICINE OF JOURNAL ENGLAND NEW
The primary endpoint was a composite of occlusion of the relevant artery at angiography, 4-8 days later, or death or further infarction before angiography. It occurred in 21.7% of the placebo group but only 15% of the group taking clopidogrel. No follow-up beyond 30 days is reported, but since many studies have shown that short term angiographic findings after myocardial infarction predict prognosis, it seems likely that this simple extra intervention will result in long term benefit.
New England Journal of Medicine 2005;352: 1179-89
Celecoxib and non-selective NSAIDs don't increase the risk of myocardial infarction
Last year, as everyone must know by now, the cyclooxygenase-2 (COX-2) selective inhibitor rofecoxib was withdrawn because of worries about its cardiac safety. The question, of course, is whether these doubts also extend to other COX-2 selective inhibitors and to non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Probably not, is the answer, according to a study from Quebec.
Using health insurance and vital statistics databases, the investigators nested a case-control study within a cohort of 113 927 people without a history of myocardial infarction who had been prescribed an NSAID between January 1999 and June 2002. During a mean follow-up of 2.4 years, 2844 people from the cohort were hospitalised for myocardial infarction. Current users of rofecoxib were at increased risk of myocardial infarction (relative risk 1.24, 95% CI 1.05 to 1.46) compared with those who had not used an NSAID in the previous year. In contrast, there was little to suggest any increased risk in current users of celecoxib (0.99, 0.85 to 1.16), although few were taking more than 200 mg a day. The study turned out to have too little statistical power to exclude meaningful differences in risk associated with traditional NSAIDs (1.00, 0.73 to 1.37), naproxen (1.17, 0.75 to 1.84), or meloxicam (1.06, 0.49 to 2.30).
The researchers reckon that their results provide evidence against a broad class effect for COX-2 inhibitor mediated cardiotoxicity. Even so, they advise that new agents with COX-2 inhibitory potency similar to or greater than that of refecoxib should be used only with extreme caution.
Annals of Internal Medicine 2005 April 5 (www.annals.org/cgi/content/full/0000605-200504050-00113v1)
Morphine plus gabapentin is effective for neuropathic pain
Neuropathic pain is a miserable condition interfering with sleep, work, and the enjoyment of life in general. It's a common complication of diabetes, herpes zoster, and several other conditions that cause nerve damage. A wide range of drugs (including anticonvulsants, antidepressants, and analgesics) is used in its management, but it's often not very responsive to treatment. Although trials have shown that several drugs produce modest benefit, patients often find that doses high enough to be effective produce intolerable adverse effects.
The combination of gabapentin and morphine (given orally in a sustained release formulation) seems to be better than either of these drugs given as a single agent. Fifty seven patients with either diabetic neuropathy or postherpetic neuralgia took part in a crossover trial in which they received placebo, morphine, gabapentin, or a combination of gabapentin and morphine in random order during successive five week periods. Pain scores were lowest during treatment with the gabapentin-morphine combination. This treatment was also associated with less pain-related interference with mood and with higher scores for vitality and social functioning, but at the maximum tolerated dose the combination caused a higher frequency of constipation than gabapentin alone and a higher frequency of dry mouth than morphine alone.
Credit: MEDICINE OF JOURNAL ENGLAND NEW
The trial used an active placebo to minimise inadvertent unblinding. Only a quarter of the participants correctly identified when they were receiving the gabapentin-morphine combination, which is no more than would be expected by chance.
It's not clear whether gabapentin and morphine act synergistically or even additively to produce this analgesic effect. But, as the authors argue, a combination with less than additive effects may be clinically useful provided that the adverse effects show even less additivity.