Data from the ADVANCE study (Action in Diabetes and Vascular Disease) presented by Stephen MacMahon, MD, The George Institute for International Health, Australia, demonstrated that lowering blood pressure in patients with diabetes significantly reduces mortality. The benefits were evident independent of baseline blood pressure and whether patients were receiving concomitant treatment with other blood pressure-lowering, lipid-lowering, or antiplatelet therapies.

The UK Prospective Diabetes Study showed that lowering systolic blood pressure (SBP) from 155–145 mmHg in diabetic patients with hypertension resulted in a significant reduction in mortality (Turner R et al. BMJ 1998). The objectives of the current study were to determine whether additional benefits could be achieved by further lowering SBP to <145 mmHg, whether the benefits would be similar for non-hypertensive patients, and whether those benefits would be in addition to those produced by other cardiovascular preventive therapies.

The study population included 11,140 patients (mean age 66 years; mean SBP 145 mmHg) who were randomly assigned to receive combination perindopril/indapamide 2.0mg/0.625mg for 3 months followed by 4.0mg/1.25mg thereafter (n=5,569) or placebo (n=5,571). Patients received ancillary treatment at the discretion of the treating physician. The primary study outcomes were macrovascular (nonfatal stroke or MI or death from any cardiovascular cause) and microvascular events (new or worsening nephropathy or diabetic eye disease).

Baseline patient characteristics were similar between groups. Average patient follow-up was 4.3 years at which point 73% of those receiving active therapy and 74% of those receiving placebo remained on therapy. Mean systolic and diastolic blood pressure (DBP) declined by 5.6 and 2.2 mmHg, respectively, in patients receiving combination perindopril/indapamide vs placebo (p<0.001 for both systolic and DBP). Blood pressure dropped from 145/81 mmHg at baseline to 135/75 mmHg in the treatment arm and 140/77 mmHg in the control group.

In patients receiving combination perindopril/indapamide there was a significant relative risk reduction (RRR) of 14% in all-cause mortality (p=0.025) which was driven primarily by an 18% RRR in cardiovascular deaths (p=0.027).

The overall RRR of a macrovascular or microvascular event was 9% (p=0.041).

Additional secondary endpoint analyses showed a 14% reduction (8.4% vs 9.6%, p=0.020) in the risk for coronary heart disease and a 21% reduction (22.3% vs 26.9%, p<0.0001) in all renal events. There was no difference in cerebrovascular or diabetic eye events. Similar benefits were achieved for those with or without hypertension and in the presence or absence of treatment with other blood pressure lowering drugs, statins, or anti-platelet drugs (Table 1).

Prof. MacMahon called for routine blood pressure reduction for all patients with type 2 diabetes. “In absolute terms”, said Prof. MacMahon, “one death would be avoided for every 78 patients treated with the fixed combination of perindopril and indapamide over 5 years. Lowering blood pressure is what counts, not the way by which it is lowered”