Aggressive BP Therapy Reduces Vascular Events in Diabetic Patients

Internal Medicine World Report, November 2007, Volume 0, Issue 0

VIENNA, Austria—Intensive blood pressure (BP) therapy, regardless of any evidence of hypertension, reduces mortality and major vascular events in patients with type 2 diabetes, said Stephen MacMahon, PhD, at the European Society of Cardiology annual meeting.

In the largest clinical trial to date to examine the prevention of complications in diabetes, a fixed-dose combination of the angiotensin-converting-enzyme (ACE) inhibitor perindopril (Aceon) and the diuretic indapamide (Lozol) was associated with a 14% reduced risk of death from any cause compared with placebo in patients with type 2 diabetes who were already well treated, many with other antihypertensive agents, said Dr MacMahon, principal director, the George Institute for International Health, and professor of cardiovascular medicine and epidemiology at the University of Sydney in Australia.

The 20-center Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) study included 11,140 patients (aged >55 years) who were at high risk of cardiovascular (CV) disease. They were randomized to perindopril/indapamide (initiated at 2.0/0.625 mg/d; titrated to 4.0/1.25 mg/d after 3 months) on top of existing therapies or to placebo.

At study entry, mean BP was 145/81 mm Hg; mean age was 65.8 years.

The average systolic BP was reduced by 5.6 mm Hg, and the average diastolic BP was reduced by 2.2 mm Hg in the patients allocated to perindopril/ indapamide compared with placebo.

After a mean follow-up of 4.3 years, the primary outcome—the combined incidence of macrovascular and microvascular events—was 9% lower in the group randomized to perindopril/indapamide. In addition to the reduction in total mortality, an 18% relative reduction in CV death and a 21% relative reduction in the incidence of renal events were also observed with perindopril/indapamide.

"These benefits were achieved in a population with good control of risk factors," said Dr MacMahon. At the first visit, 75% were taking antihypertensive drug therapy (in addition to the study drug). Other proven CV risk reduction therapies (eg, aspirin, statins) were widely used.

There was no reduction in the risk of cerebrovascular events in the combination group, but the total number of such events may have been too small to show a difference, he said. The incidence of new or worsening microvascular eye disease was also not affected by the study treatment.

The reduction in mortality with BP therapy was apparent in those with or without hypertension and regardless of background therapy with an ACE inhibitor. "We added treatment to everybody, irrespective of blood pressure and with no blood pressure goals," said Dr MacMahon. "The critical issue is to get every patient on treatment."

Dr MacMahon said the study supports current guidelines that recommend a BP target of <130/80 mm Hg in patients with diabetes who do not have evidence of hypertension.

Sidney Smith, MD, questioned whether nonhypertensive patients in the study benefited from further treatment. Nevertheless, he continued, "The trial is important in my thinking," in that it confirms the importance of BP lowering in the diabetic population, although the BP target in this population remains undefined.

Whether mechanisms other than BP reduction can explain the findings from this study is also unknown, said Dr Smith, professor of medicine and director of the Center for Cardiovascular Science and Medicine at the University of North Carolina, Chapel Hill.


The study appeared online ( 2007;370:829-840) to coincide with the conference. In an accompanying editorial (pages 804-805), Norman M. Kaplan, MD, wrote, "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."