The HOPE study and diabetes

The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators (Jan 22, p 253)1Heart Outcomes Prevention Evaluation (HOPE) Study InvestigatorsEffects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy.Lancet. 2000; 355: 253-259Summary Full Text Full Text PDF PubMed Scopus (3298) Google Scholar report that ramipril given to people with diabetes mellitus lowered the risk of major cardiovascular outcomes by 25–30%. They claim that the effect was apparent irrespective of whether participants had a history of cardiovascular events, hypertension, or microalbuminuria, were taking insulin or oral hypoglycaemic agents, or had type-1 or type-2 diabetes mellitus. The investigators also state that ramipril lowered the risk of overt nephropathy, renal failure, or laser therapy, and that it had no long-term effect on glycaemic control. Although these results are interesting, several critical points can be raised, and it can also be argued that the new information given in the paper is limited. Figure 2 shows that the relative risk reduction in subgroups without microalbuminuria, with no cardiovascular disease and with type-1 diabetes do not reach significance despite high numbers of patients: without microalbuminuria (n=2437) and with no cardiovascular disease (n=1119). Since more than 98% of the patients had type-2 diabetes mellitus it is obvious that no conclusions of the effect of ramipril in type-1 diabetes mellitus can be drawn from the study. Thus, only in patients with diabetes with microalbuminuria or cardiovascular disease, or both, at high risk of having cardiovascular events, is the relative risk reduction significant. No data on metabolic control and blood pressure as absolute figures are given in the paper. We are only told that blood pressure and glycated haemoglobin (HbA1c) are significantly lower in the ramipril group, but for HbA1c the difference is not shown. Thus, it can be argued that the findings in this study only confirm what has been shown in the UK Prospective Diabetes Study.2UK Prospective Diabetes Study (UKPDS) GroupEfficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39.BMJ. 1998; 317: 713-720Crossref PubMed Google Scholar In the conclusion the investigators claim that ramipril lowered the risk of nephropathy, renal failure, or laser therapy. Ramipril does indeed reduce the risk of developing nephropathy in patients with microalbuminuria, as previous studies have shown.3Ravid M Lang R Rachmani R Lishner M Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus: a 7 year follow-up study.Arch Intern Med. 1996; 156: 286-289Crossref PubMed Scopus (0) Google Scholar However, table 3 shows that there was no effect on laser therapy (p=0·70) nor dialysis (p=0·70) in the ramipril group. The results of the HOPE study in patients with diabetes mellitus are important but mostly because they confirm previous studies. The study underlines the importance of strict metabolic control and aggressive antihypertensive treatment in high-risk patients with type-2 diabetes who have cardiovascular disease or microalbuminuria. However, it is not shown that patients with uncomplicated type-2 diabetes, with only one additional risk factor, will benefit from angiotensin-convertingenzyme (ACE) inhibitor treatment. Nor is it shown that there are new effects of ACE-inhibitors on end-stage manifestations of diabetic nephropathy or proliferative retinopathy. The HOPE study and diabetesAuthors' reply Full-Text PDF