To assess the effect of blood-pressure lowering drugs on clinical outcomes in patients with prior stroke or transient ischaemic attack.

The following sources were searched: unspecified databases, INDANA, specialised and general medical journals, specialised congress proceedings, and overviews. The investigators involved in such trials were contacted directly for additional studies. Details of the years searched and the search terms used were not provided.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) that met the inclusion criteria were included. Some trials only included participants with stroke, whilst others had a less-specific population that included a small number of people with stroke (0.2 to 100% of the total trial participants).

Specific interventions included in the review

Antihypertensive drug treatment comprising a fixed combination of deserpidine and methyclothiazide or other unnamed drugs, compared with placebo, no intervention or normal care.

Participants included in the review

Survivors of stroke or transient ischaemic attack.

Outcomes assessed in the review

The following outcomes were assessed.

1. Fatal stroke.

2. Fatal and nonfatal strokes excluding transient ischaemic attacks.

3. Fatal coronary events including sudden death, which was defined as death occurring within 24 hours after any symptom.

4. Fatal and nonfatal main coronary events using the patients' history as the criterion for main coronary heart disease in the Hypertension Detection and Follow-up Programme.

5. Cardiovascular mortality including death from thromboembolism.

6. Main cardiovascular events, combining 2, 4 and 5, but excluding non major cardiovascular events such as angina pectoris, intermittent claudication, or nonfatal congestive heart failure.

7. Total mortality. The primary outcome was stroke reoccurrence.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

The authors do not report the method used to assess validity, or how the validity assessment was performed.

The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.

How were the studies combined?

The relative risk was estimated from the summarised data. The number of stroke patients in some subgroups of the individual data analysis of antihypertensive intervention (INDANA) trials was small, and consequently, the data from these trials were pooled to avoid the dispersion of treatment effect estimates, and to address the issue of no outcomes in the treatment groups of some trials.

How were differences between studies investigated?

To take into account the differences in the length of follow-up between trials, the number of patient-years by trial and by group was used as the denominator, rather than the number of patients. Three groups were distinguished according to sources of data: a previous meta-analysis, the INDANA trials, and the Post-stroke Antihypertensive Treatments (PATS) study. The groups were presented separately and combined as if there was no heterogeneity. A sensitivity analysis was performed, including and excluding the biggest trial.

Nine trials with a total of 6,752 participants were included: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); one trial included stroke survivors, whether hypertensive or not (5,665 participants). The size of the trials ranged from 11 to 2,841 participants.

All strokes.

Combining the trials from the previous meta-analysis with the INDANA trials, treatment reduced the risk of stroke in relative terms by 29% (95% confidence interval, CI: 5, 47, p=0.03). The estimates limited to one of these groups did not reach statistical significance. The point estimate was similar to that from the PATS trials, which alone was highly significant (p=0.0013), and the overall risk reduction was 28% (95% CI: 15, 39, p=0.00009).

Interaction between treatment effect for stroke and history of prior stroke or transient ischaemic attack.

The odds ratio (OR) for INDANA individuals without a history of stroke or transient ischaemic attack (18,491 participants) was 0.57 (95% CI: 0.49, 0.67), whereas the OR for those with a history of stroke or transient ischaemic attack (536 participants) was 0.73 (95% CI: 0.43, 1.22). The OR for INDANA data as a whole (19,027 participants) was 0.58 (95% CI: 0.50, 0.68).

Overall relative risks for all outcomes.

The overall relative risks were calculated by combining data from all the trials. The overall relative risk was 0.86 (95% CI: 0.73, 1.02, p=0.078) for total mortality; 0.77 (95% CI: 0.63, 0.95, p=0.016) for cardiovascular mortality; 0.79 (95% CI: 0.68, 0.91, p=0.0013) for major cardiovascular events; 0.71 (95% CI: 0.53, 0.94, p=0.019) for fatal strokes; 0.72 (95% CI: 0.61, 0.85, p=0.00009) for all strokes; 0.88 (95% CI: 0.58, 1.36, p=0.57) for fatal coronary events; and 1.08 (95% CI: 0.58, 1.36, p=0.66) for all major coronary events.

Blood-pressure lowering drug interventions reduced the risk of stroke reoccurrence in stroke survivors. The available data did not allow the verification of whether such benefit depends on the initial blood-pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.

This was a well-written review with a good discussion of the results and issues surrounding the subject. The discussion included some of the limitations of the review, for example: the use of subgroups of patients from trials; the inclusion of transient ischaemic attacks, which are difficult to accurately diagnose; the focus on any stroke rather than severe stroke; the possibility that information may have been missed; the heterogeneity of the results; and the fact that one trial (the PATS trial) represented over three quarters of the data, and therefore, the results were essentially representative of those results.

The search strategy could have been described in more detail, although the authors acknowledged the possibility that relevant data might have been missed. No details were provided on how validity was assessed, how decisions to include trials were made, or how the data were extracted. The authors described a number of outcomes but a significant benefit was only shown for one (reoccurrence of stroke). Side-effects were not reported. Overall, the authors' conclusions are supported by the evidence offered.

Trials must now assess the effect of blood-pressure lowering drugs in normotensive patients at high risk of stroke.

Association pour la Promotion de la Recherche et de l'Evaluation en Therapeutique; Societe Francaise d'Hypertension Arterielle; Fondation pour la Recherche Medicale; Hospices Civils de Lyon.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.