Inpharma 1308 - 6 Oct 2001

Wang say that the target should be normal BP (<Combination antihypertensive130/85mm Hg) and note that combination therapy willtherapy lowers stroke risk be required in most patients to achieve this level of BPcontrol.Combination therapy with perindopril and

As increasing numbers of patients will be eligible forindapamide lowers the risk of stroke in patients with aBP-lowering therapy on the basis of the findings ofhistory of stroke or transient ischaemic attack (TIA),PROGRESS, Drs Staessen and Wang say that furtherreports the multinational PROGRESS* Collaborativeresearch should be conducted to clarify whether drugGroup.1classes that are more expensive than diuretics (such asPROGRESS involved 6105 patients with a history ofACE inhibitors) should be used as initial BP-loweringstroke or TIA during the previous 5 years who weretherapy for secondary stroke prevention.considered to have no definite indication for, or

contraindication to, ACE inhibitor therapy.** Patients * Perindopril Protection Against Recurrent Stroke Studywere randomised to receive active therapy based on ** The study was supported in part by Servier.perindopril 4 mg/day (n = 3051) or placebo. Of the

1. PROGRESS Collaborative Group. Randomised trial of a perindopril-basedpatients who were judged to have no specific indication blood-pressure-lowering regimen among 6105 individuals with previous stroke

or transient ischaemic attack. Lancet 358: 1033-1041, 29 Sep 2001.for, or contraindication to, diuretic treatment, those in2. Staessen JA, et al. Blood-pressure lowering for the secondary prevention ofthe active therapy group received additional indapamide stroke. Lancet 358: 1026-1027, 29 Sep 2001.

2 or 2.5 mg/day and those in the placebo group received 800840842

a second placebo (1770 and 1774 patients, » Editorial comment: Results from this study were presentedrespectively). The mean duration of follow-up was 3.9at the 17th World Congress of Neurology, held in London, UK,years. in June 2001 [see Inpharma 1297: 14, 21 Jul 2001; 800840675].

Risk reduction for different stroke subtypesDuring follow-up, stroke occurred in 10 and 14% of

patients in the active therapy and placebo groups,respectively (relative risk reduction 28%; 95% CI17–38%). The benefit of active therapy was seen for fatalor disabling strokes and for less severe strokes, and forischaemic stroke or cerebral haemorrhage. Activetherapy, compared with placebo, was also associatedwith a reduction in the risk of major vascular events(relative risk reduction 26%; 95% CI 16–34%).

Recipients of perindopril plus indapamide, comparedwith double placebo, had a significantly lower strokerisk (relative risk reduction 43%; 95% CI 30–54%) andrisk of any major vascular event (40%; 29–49%); suchsignificant differences were not seen when recipients ofperindopril alone were compared with patients givensingle placebo. The researchers note that there wassignificant heterogeneity in the magnitude of thesetreatment effects. Reductions in the risks of stroke andmajor vascular events were similar among patients withor without hypertension; in both of these patientsubgroups, perindopril plus indapamide seemed toprovide similar advantages over perindopril alone.

Therapeutic implicationsThe researchers conclude that their findings ‘should

have implications for the care of a large proportion of allpatients who survive stroke or transient ischaemicattack’. They suggest that for patients presenting withacute stroke or TIA, starting treatment at hospitaldischarge or at a post-discharge follow-up visit shouldbe considered. The researchers also believe that generalpractitioners should consider starting treatment at thenext visit in patients who have previously experienced astroke or TIA. They say that while treatment may startwith monotherapy, ‘the objective should be to movepatients onto combination therapy as soon as possible’.

Discussing the translation of these study results intoclinical practice, Drs Jan Staessen and Jiguang Wangfrom the University of Leuven, Belgium, say that untilexpert committees have reached a consensus, it wouldbe reasonable to start or intensify BP-lowering therapy inpatients who are middle aged or older, have experienceda cerebrovascular event during the period from 2 weeksto 5 years prior, are clinically stable and who have nocontraindications to such therapy.2 Drs Staessen and

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