His colleague, Professor John Chalmers, chairman of the study management group, said later: “The results clearly demonstrate that we have the tools to blunt the impact of the global diabetes epidemic, but concerted action is urgently required to ensure that patients with diabetes are identified and provided with treatments proven to improve important outcomes like survival.”
Professor Stephen Mac Mahon
With or without hypertension?
The UK Prospective Diabetes Study (BMJ 1998:317:703-713) showed that treating hypertension in people with diabetes reduced their risk of complications, but raised questions whether additional benefits could be obtained in diabetics who do not have hypertension.
The ADVANCE study, which represents the largest ever study in the treatment of diabetes, included 11,140 patients (both normotensive and hypertensive) with type 2 diabetes from 200 research centres in 20 different countries. They were randomised to receive either placebo or a fixed combination of perindopril (an ACE inibitor) and indapamide (a thiazide-like diuretic) in a single tablet once daily or placebo.
Results at 4.3 years - which were also published online yesterday by The Lancet – show a relative risk reduction of 14% in all-cause mortality among diabetics receiving the active treatment (p=0.025), a relative risk reduction of 18% for cardiovascular deaths (p=0.027), a risk reduction of 8% for non cardiovascular deaths (p=0.41) and a risk reduction of 9% for major macro or microvascular events (p=0.041).
Other results showed that the risk of coronary heart disease events was reduced by 14% and the risk of new or worsening kidney disease by 21%. This was against a background of comparatively small blood pressure reductions which were on average 5.6 mmHg systolic BP and 2.2 mm Hg diastolic BP. In absolute terms, said MacMahon, one death would be avoided for every 78 patients treated with the fixed combination of perindopril and indapamide over five years.
He added: “Similar benefits were achieved for those with or without hypertension and in the presence or absence of treatment with ACE inhibitors, other blood pressure lowering drugs, statins, and aspirin.”
MacMahon also noted that, because adherence rates at the end of follow up were 73% in the active group and 74% in the placebo group, this treatment seems particularly well tolerated.
In an accompanying editorial in The Lancet, Norman M Kaplan (University of Texas Southwestern Medical Center, USA) cautioned against over-interpretation of the ADVANCE data.
He wrote: “The fixed combination of perindopril and indapamide could be the best possible protector against h y p e r t e n s i o n - r e l a t e d consequences for patients with type 2 diabetes, but I believe that other drugs – if they lower blood pressure as much and do not have metabolic side-effects – would be as protective as this combination treatment. Lowering blood pressure is what counts, not the way by which it is lowered.”
Commenting on the findings yesterday, Professor Guiseppe Mancia, chairman of the committee for the ESH/ESC Guidelines on Hypertension, said:“From ADVANCE there are real grounds to suggest that the ESC guidelines should be extended to include the starting of treatment of diabetics with normal blood pressure.” He added that there may also be a case to include patients with prediabetes.
According to the ESC, there are approximately 250 million people worldwide with type 2 diabetes, most of whom will die or be disabled by complications of their condition. And MacMahon acknowledged that the ADVANCE results were “an important step forward in health care for the millions of people with diabetes”.
ADVANCE, The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation
Read the ADVANCE Hot Line Session report