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Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review
V L Feigin1, G J Rinkel, A Algra
1University Department of Neurology, Utrecht, The Netherlands.
Insights
Calcium antagonists, including nimodipine, reduce ischemic deficits after subarachnoid hemorrhage (SAH). Nimodipine improves patient outcomes, though evidence for other calcium antagonists is inconclusive.
Area of Science:
- Neurology
- Pharmacology
- Critical Care Medicine
Background:
- Aneurysmal subarachnoid hemorrhage (SAH) carries a high risk of secondary complications, including cerebral ischemia.
- Nimodipine has shown promise in reducing secondary ischemia and improving outcomes post-SAH.
- Definitive evidence for all calcium antagonists in managing SAH complications is lacking.
Purpose of the Study:
- To systematically evaluate the efficacy of calcium antagonists in preventing poor outcomes after aneurysmal subarachnoid hemorrhage (SAH).
- To compare the effects of nimodipine, nicardipine, and AT877 against control groups in randomized trials.
- To assess the impact of early calcium antagonist treatment on ischemic events and overall patient prognosis.
Main Methods:
- Systematic overview of randomized controlled trials (RCTs) completed by January 1996.
- Included trials compared calcium antagonists with placebo or no treatment.
- Treatment initiation within 10 days of subarachnoid hemorrhage (SAH) onset was a key criterion.
Main Results:
- Calcium antagonists reduced the risk of poor outcome (death or dependency) by 16% and case fatality by 10%.
- A significant reduction in ischemic neurologic deficit (33%) and CT-documented cerebral infarction (20%) was observed.
- Nimodipine monotherapy showed a 24% reduction in poor outcome, while AT877 and nicardipine demonstrated significant reductions in cerebral vasospasm.
Conclusions:
- Calcium antagonists effectively decrease ischemic neurologic deficits following aneurysmal SAH.
- Nimodipine significantly improves overall patient outcomes within 3 months post-SAH.
- Evidence for the reduction of poor outcomes by nicardipine and AT877 remains inconclusive, and the precise mechanisms of nimodipine's benefit require further investigation.
Background And Purpose:
It has been reported that nimodipine reduces the frequency of secondary ischemia and improves outcome after aneurysmal SAH, but definitive evidence concerning all available calcium antagonists is lacking.
Methods:
Systematic overview of randomized trials that were completed by January 1996 compared calcium antagonists with control and started treatment within 10 days after onset of subarachnoid hemorrhage (SAH) was performed. All calcium antagonists studied thus far (nimodipine, nicardipine, and AT877) were included.
Results:
We analyzed 10 trials totaling 2756 patients. The relative risk (RR) reduction of poor outcome (death or dependency) was 16% (95% CI, 6 to 27%) and that of case fatality was 10% (95% CI, -6 to 25%). To prevent one poor outcome, 19 (12 to 59) patients need to be treated. Calcium antagonists give a 33% (95%, CI 25 to 41) RR reduction in the frequency of ischemic neurologic deficit and a 20% (95% CI, 11 to 28) RR reduction in the frequency of CT-scan documented cerebral infarction. Eight (6 to 11) patients need to be treated to prevent one ischemic neurologic deficit. In the analyses for nimodipine only, treatment was associated with a 24% RR reduction of poor outcome (95% CI, 12 to 38). To prevent one poor outcome, 13 (8 to 30) patients need to be treated with nimodipine. The RR reduction of angiographically detected cerebral vasospasm was statistically significant for AT877 (38%; 95% CI, 17 to 54%) and nicardipine (21%; 95% CI, 6 to 34%) but not for nimodipine (9%; 95% CI, -2 to 19%).
Conclusion:
Calcium antagonists reduce the proportion of ischemic neurologic deficits and nimodipine improves overall outcome within 3 months of aneurysmal SAH; evidence for a reduction of poor outcome from all causes by nicardipine and AT877 is inconclusive. The intermediate factors by which nimodipine exerts its beneficial effect remain uncertain.