Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Calcium antagonists reduce death and dependence in subarachnoid hemorrhage

ACP J Club. 1998 Sep-Oct;129:30. doi:10.7326/ACPJC-1998-129-2-030

Source Citation

Feigin VL, Rinkel GJ, Algra A, Vermeulen M, van Gijn J. Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage. A systematic review. Neurology. 1998 Apr;50:876-83.



In patients with aneurysmal subarachnoid hemorrhage, can calcium antagonists improve outcome? Do calcium antagonists exert their action by reducing secondary ischemia?

Data sources

Studies were identified by searching an electronic database (1966 to 1995) and the trials register of the Cochrane Stroke Review Group; scanning the reference lists of studies, review articles, and books on stroke; searching conference proceedings; and contacting pharmaceutical companies and authors of trial reports.

Study selection

Studies were selected if they were randomized controlled trials that compared any calcium antagonist drug with a control and if treatment was started within 10 days of onset of subarachnoid hemorrhage. Studies were excluded if treatment allocation was not concealed.

Data extraction

2 reviewers independently extracted data on study characteristics, death, poor outcome (i.e., death or dependence), secondary ischemia, cerebral vasospasm, rebleeding, and adverse effects.

Main results

10 studies involving 2756 patients (mean age range 44 to 56 y) with 1 to 3 months of follow-up met the inclusion criteria. Meta-analysis was done using intention-to-treat analyses. In 7 studies, calcium antagonists compared with control had a reduced risk for a poor outcome (i.e., death or dependence) { P = 0.004}* (Table). Calcium antagonists reduced the risk for secondary ischemia-related neurologic deficit or cerebral infarction on computed tomography (10 studies) (Table). A trend toward risk reduction for rebleeding (6 studies) and death (9 studies) existed for calcium antagonists.


Calcium antagonists reduce the risk for death and dependence, secondary ischemia-related neurologic deficit or cerebral infarction on computed tomography, and vasospasm within 3 months of onset of aneurysmal subarachnoid hemorrhage.

Sources of funding: Netherlands Heart Foundation and, in part, by Utrecht University Hospital.

For correspondence: Dr. G.J. Rinkel, Department of Neurology, University Hospital of Utrecht, P.O. Box 85500, 3500 GA Utrecht, The Netherlands. FAX 31-30-2533388.

* P value calculated from data in article.

Table. Calcium antagonists vs control in aneurysmal subarachnoid hemorrhage†

Outcomes at 1 to 3 mo Weighted event rates RRR (95% CI) NNT (CI)
Calcium antagonist Control
Poor outcome 25% 30% 18% (7 to 27) 21 (13 to 62)
Ischemia-related deficit NA NA 33% (25 to 41) 8 (6 to 11)
Cerebral infarction NA NA 21% (11 to 28) 10 (7 to 18)

†NA = not available; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from data in article.


One of the most controversial issues in the management of patients with subarachnoid hemorrhage is whether they should receive prophylaxis with calcium antagonists to prevent vasospasm and delayed ischemic deficits. Among clinicians, opinions are bitterly divided. Those who oppose the use of calcium antagonists note that these agents may induce substantial hypotension, a clearly dangerous event in this patient population. Feigin and colleagues provide a systematic review and meta-analysis of the most important clinical investigations addressing this problem. Although it can be argued that the evidence provided by their review is not conclusive, particularly because of the inherent limitations of meta-analyses, the data are sufficiently compelling to weight the therapeutic considerations in favor of the use of calcium antagonists in patients with subarachnoid hemorrhage. Thus, when every aspect of the topic is taken into account, patients with subarachnoid hemorrhage are better off if calcium antagonists are part of their treatment.

The final recommendations of the authors seem clear and practical: Use oral nimodipine whenever possible, reserving intravenous nicardipine for patients who require parenteral drug administration. Finally, I must emphasize the danger of hypotension and its potentially deleterious consequences when either of these drugs is used. Calcium antagonists should be given to patients with subarachnoid hemorrhage, under strictly monitored conditions by experienced personnel.

Camilo R. Gomez, MD
Comprehensive Stroke CenterBirmingham, Alabama, USA