Original HOPE study (1):
designed to investigate the effects of taking an ACE inhibitor ramipril and/or vitamin E for at least 4 years, on a wide range of vascular endpoints
total of 9541 patients (men and women) older than 55 years took part in study
patients were included if they were at high risk of cardiovascular events due to history of diabetes, previous ischaemic heart disease, peripheral vascular disease or stroke
treatment benefits of ramipril were seen across all patient groups - these benefits occurred within 3 to 4 months of starting treatment with ramipril
results revealed that the combined reduction in myocardial infarction, cardiovascular death and stroke at 5 years was 22 % in the ramipril treatment group; there was a 17% reduction in all cause mortality in the ramipril treatment group; no effect on stated endpoints occurred with patients treated with vitamin E
the study investigators do not attribute treatment benefits accrued with ramipril to be because of an impact on blood pressure - the baseline blood pressure had a mean level of 139/79 mmHg - by the end of the trial there had only been a small further decline
HOPE follow-up study (2):
a follow-up study based on the HOPE study population has been undertaken
4,528 patients agreed to further follow-up (median follow-up period 2.6 years)
rates of use of angiotensin-converting-enzyme inhibitors (ACEIs) in the 2 groups (72% ramipril versus 68% placebo) were similar after the end of the trial
during the post-trial follow-up, patients allocated to ramipril had a 19% further lower relative risk (RR) of myocardial infarction (MI), a 16% lower RR of revascularization, and a 34% lower RR of a new diagnosis of diabetes
RR reductions in vascular events were observed during and after the active phase of the trial, regardless of baseline risk (RR of 0.76, 0.89, and 0.83 for low-, medium-, and high-risk patients, respectively) or ancillary treatments (RR of 0.90 for aspirin, 0.76 for beta-blockers, and 0.84 for lipid-lowering medication)
the study authors noted that the benefits of ramipril observed during the active period of the HOPE trial were maintained during post-trial follow-up for cardiovascular death, stroke, and hospitalisation for heart failure
additional reductions in MI, revascularization, and the development of diabetes were observed during the follow-up phase despite similar rates ACEI use in the 2 randomized groups
benefits associated with ACEI use were consistent regardless of patient risk or ancillary treatments
the benefits observed in the study extension data indicate that the 4.5 years of initial, "earlier" use of ramipril therapy provided a longer-term protective effect compared with later initiation
during the follow-up period, there was not observed an additional treatment effect for stroke
blood pressure was similar during the post-trial follow-up and suggests that an important mechanism by which strokes may have been reduced during the blinded part of the study (where there was a modest difference in blood pressure of 3/2 mm Hg) was blood pressure lowering
the study authors concluded that ACE inhibitor therapy should be used in most patients with vascular disease or diabetes and additional CV risk factors
Vitamin E in the prevention of cardiovascular disease:
study evidence (1,3) has provided no evidence of benefit of vitamin E supplementation in the prevention of the development cardiovascular disease
Vitamin C supplementation in the prevention of cardiovascular disease:
in a large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events (3)
Homocysteine lowering therapy and stroke risk (4)
HOPE 2 investigators have analyzed stroke outcomes among participants of the HOPE 2 trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo, for 5 years
among 5522 participants, stroke occurred in 258 (4.7%) individuals during a mean of 5 years of follow-up. The geometric mean homocysteine concentration decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group
the incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group - the hazard ratio
, 0.75; 95% (CI, 0.59-0.97) was significant
vitamin therapy also significantly reduced the risk of nonfatal stroke (HR, 0.72; 95% CI, 0.54-0.95) but did not impact on neurological deficit at 24 hours (P=0.45) or functional dependence at discharge or at 7 days (OR, 0.95; 95% CI, 0.57-1.56)
this study data suggests that homocysteine lowering therapy may have a role in lowering stroke risk
a meta-analysis has suggested that folic acid reduces risk of stroke (5)
Reference:
1. New England Journal of Medicine 2000; 342: 145-53.
2. Bosch J et al. Long-term effects of ramipril on cardiovascular events and on diabetes: results of the HOPE study extension.Circulation. 2005 Aug 30;112(9):1339-4
3. Sesso HD et al.Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33.
4. Saposnik G et al.; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trialStroke. 2009 Apr;40(4):1365-72.
5) Wang X et al.Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.Lancet. 2007 ;369:1876-82.
