Suggested updated model for blood pressure lowering

Andreas Terént

Department of Medical Sciences, Akademiska Hospital, Uppsala, Sweden

In the consensus statement of 2002, which was mainly based on the first publication of the PROGRESS trial (1), it was concluded that:

  • lowering of blood pressure is effective in secondary prevention after stroke and TIA
  • ACE inhibitors and diuretics reduce the risk of stroke
  • this treatment is safe and well-tolerated
  • other blood pressure lowering agents may be effective
  • treatment should be considered in all patients
  • the target level of blood pressure control has not yet been defined
  • starts with a thiazide 2 weeks after stroke, an ACE-inhibitor is added
  • alert on adverse effects

Since then, evidence has become stronger by the publication of a systematic review of blood pressure reduction and secondary prevention of stroke (2) and an overview of blood pressure lowering and stroke in general (3). Additional papers from the large PROGRESS trail, which included 6105 patients, have also been published (4-8). Moreover, new data on the treatment with an angiotensin receptor blocker (ARB) in the acute phase of stroke have been presented (9). Preliminary data on ARB therapy versus treatment with calcium channel antagonists (CCA), in a trail similar to but smaller than PROGRESS has been presented (10).

According to the systematic review, secondary prevention by BP lowering is effective for most drugs, except for betablockers (3). The strongest preventive effect is achieved by the combination of ACE-inhibitors (ACEI) and diuretics, which reduce the risk of stroke and the risk of cardiac events to the same degree. Single-therapy with diuretics reduces the risk of stroke, but has no significant impact on cardiac events. The outcome of single-therapy with ACEIs is the opposite, i.e. cardiac events are reduced but not stroke.

In the overview of published reviews, both primary and secondary prevention trials were included (4). In this study, it was shown that ACE-inhibitors, calcium antagonists, betablockers and diuretics are effective. Each 10 mm Hg reduction in systolic blood pressure (SBP) is associated with a decrease in the risk of stroke by one third in patients aged 60 to 79 years. The association between SBP and stroke risk is continuous down to levels of at least 115/75 mm Hg. In PROGRESS, the blood pressure reduction was on an average 9/4 mm Hg during a 4-year period. As regards age, patients in PROGRESS mainly were in the age interval 54-74 years (1).

From the PROGESS trial, important data on the risk for dementia and cognitive decline have been derived (5). Dementia was documented in 6% of actively treated patients and 7% of the patients in the placebo group, a non-significant difference. Cognitive decline appeared, on the other hand, in a significantly lower proportion of actively treated patients, 9% versus 11%. This lower frequency was associated with a lower risk of stroke recurrence in actively treated patients. These data are of great importance as the beneficial trend for active therapy was seen in hypertensive as well normotensive stroke patients. In diabetic patients, the PROGRESS trial showed that lacunar infarction was reduced by active therapy (6).

An ARB was used in the ACCESS study, including 342 hypertensive patients, who were treated 30 hours after stroke (9). The number of deaths and vascular events were significantly fewer among ARB-treated patients at 1 year. However, these data are difficult to interpret as no significant difference in blood pressure was found between actively treated and placebo patients. Drug tolerance and side effects did not differ significantly between the groups. The latter observation is important, since a new and larger randomized controlled trial (RCT) is needed. Presently, acute lowering of blood pressure can only be recommended within the frame RCTs. 

Finally, preliminary data from the MOSES trial, comparing an ARB with a CCA have been presented (10). No patients were given placebo therapy in this trial, leaving the question of blood pressure reduction unanswered. The study included 1405 hypertensive (160/100 mm Hg) stroke patients. The time between the qualifying event and inclusion in the study was 11 months (in PROGRESS, patients were included after 8 months). In MOSES, blood pressure was well characterised by ambulatory blood pressure monitoring. No significant difference in blood pressure was seen between ARB and CCA treated patients during the whole follow-up period (2.5 years). In spite of that, the number of cerebrovascular events was lower in ARB-treated patients. No difference was achieved in terms of disability however.

In conclusion, we now have relevant data on the following issues that may be included in the new consensus statement:

  • overall evidence of a beneficial effect of blood pressure lowering drug therapy after stroke and TIA
  • a positive and equally strong effect is seen on stroke and cardiac events
  • a reasonably high safety is achieved for ACEIs, diuretics and probably ARBs
  • no target blood pressure can be recommended, the lower the pressure the lower the risk
  • treatment should be considered in all patients below 75 years of age
  • other drugs than ACEIs and diuretics may be useful provided that systolic blood pressure is reduced by ~10/5 mm Hg
  • the start of drug therapy should be delayed by two weeks
  • acute blood pressure lowering is only recommended within the frame of RCTs

References

1.        PROGRESS collaborative group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033-1041.

2.        Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events. A systematic review. Stroke 2003;34:2741-2749.

3.        Lawes C, Bennett D, Feigin V, Rodgers A. Blood pressure and stroke. An overview of published reviews. Stroke 2004;35:1024-1033.

4.        PROGRESS collaborative group. Effects of a perindopril-based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease. Eur Heart J 2003;24:475-484.

5.        PROGRESS collaborative group. Effects of blood pressure lowering with perindopril and indapamid therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003;163:1069-1075.

6.        Berthet K, Neal B, Chalmers J, MacMahon S, Bousser MG, Colman S, Woodward M. Reductions in the risk of recurrent stroke in patients with and without diabetes. The PROGRESS trial. Blood Pressure 2004;13:7-13.

7.        Rodgers A, Chapman N, Woodward M, Liu LS, Colman S, Lee A, Chalmers J, MacMahon S. Perindopril-based blood pressure lowering in individuals with cerebrovascular disease: consistency of benefits by age, sex and region. J Hypertension 2004;22:653-659.

8.        Ohkubo T, Chapman N, Neal B, Woodward M, Omae T, Chalmers J. Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk. Am J Respir Care Med 2004;169:1041-1045.

9.        Schrader J, Lüders S, Kulschewski A, Berger J, Zidek W, Treib J, Einhäupl K, Diener HC, Dominiak P. The ACCESS study. Evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke 2003;34:1699-1703.

10.     Schrader J, Zidek W, Diener HC, Küppers H, Lüders S. MOSES (Morbidity and mortality after stroke), eposartan versus nitredipin in secondary prevention. Presentation of final results. Satellite Symposium, ESC Congress, August 30, 2004.

 

 

 

 
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