HOPE for Stroke
The Heart Outcomes Prevention Evaluation Study (HOPE) was a landmark trial demonstrating beneficial effects of the angiotensin converting enzyme ramipril on cardiovascular events and disease progression. Several lines of evidence suggest that ACE inhibitors may also lower the risk of ischemic vascular events. ACEIs reduce proliferation of vascular smooth muscle, enhance endogenous fibrinolysis, stabilize plaques and decrease angiotensin II mediated atherosclerosis, plaque rupture and vascular occlusion. These effects suggest that they may reduce transient ischemic events through mechanisms that are independent of reduction in blood pressure. The results of the HOPE trial support this hypothesis.
The primary outcome of HOPE was the composite end point of myocardial infarction, stroke or cardiovascular death, and individual components were analyzed separately. Reduction in blood pressure was modest; however, the relative risk of any stroke was reduced by 32% in the ramipril group compared with the placebo group, and the relative risk of fatal stroke was reduced by 61%.
Benefit was seen at all values of diastolic and systolic blood pressure, confirming that the beneficial effects of ramipril were not confined to those with 'high' blood pressure. The reduction in strokes was consistent across the various subgroups examined, including patients receiving antiplatelet treatment and lipid-lowering drugs. The benefits were also consistent across subgroups defined by the presence or absence of previous stroke, coronary artery disease, peripheral arterial disease, diabetes or hypertension.
These results support those of the PROGRESS trial (perindopril protection against recurrent stroke study), which found that perindopril in combination with indapamide reduced the risk of recurrent strokes by 28% in patients with previous cerebrovascular disease.2,3 The initial blood pressure in this study was higher than in HOPE, and, therefore, was lowered more substantially. Taken together, results from both studies suggest that ACE inhibitors are of benefit in both primary and secondary prevention, even in patients without hypertension. The authors conclude that patients who are at high risk of stroke should be treated with ramipril, irrespective of their initial blood pressure levels and in addition to other preventive treatments such as blood pressure lowering agents and aspirin.
Critics of the study point out that the absolute risk reduction and number needed to treat are not available and do not necessarily support the authors' conclusions.
Source
- Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002; 324:1-5.
- Neal B, MacMahon S. PROGRESS (perindopril protection against recurrent stroke study): rationale and design. J Hypertens 1995; 13: 1869-73.
- PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033-41.
