Antihypertensive Therapy In Type 2 Diabetes Mellitus

Journal of Family Practice, Dec, 1998 by William F. Miser

UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 317:713 20.

Clinical question Which antihypertensive is more efficacious in preventing complications in people with type 2 diabetes mellitus: an angiotensin-converting enzyme inhibitor (captopril) or a beta-blocker (atenolol)?

Background Sixty-five percent of patients with type 2 diabetes also have hypertension, and less than half have adequate control of their blood pressure. Because hypertension potentiates the macrovascular and microvascular complications of diabetes, the American Diabetes Association advises strict blood pressure control.[1,2] Conventional teaching has recommended angiotensin-converting enzyme (ACE) inhibitors as the antihypertensive of choice and the avoidance of beta-blockers in people with diabetes; however, no studies have directly compared the effectiveness of these 2 drugs.

Population studied Newly diagnosed patients with type 2 diabetes, aged 25 to 65 years, who were enrolled in the UK Prospective Diabetes Study (UKPDS) and who also had hypertension were included. Patients were excluded if they had a strict requirement for blood pressure control or beta-blockade, severe vascular disease, severe concurrent illness, or contraindications to beta-blockers.

Study design and validity This was a randomized controlled trial and a subanalysis of a larger long-term study.[3] Subjects who were randomized to the group requiring tight control of blood pressure were subsequently randomized to receive either captopril, 25 mg (up to 50 mg) twice daily, or atenolol, 50 mg (up to 100 mg) once daily, as an initial antihypertensive. If a blood pressure of [is less than] 150/85 mm Hg was not achieved, other agents (furosemide, slow-release nifedipine, methyldopa, and prazosin) were subsequently added. The investigators followed these patients for 9 years and compared the development of complications and side effects of treatment with captopril or atenolol, using an intention-to-treat analysis.

The investigators and the subjects were aware of which medications the patients were taking, and this absence of blinding could potentially introduce a bias. For example, a patient known to be on an ACE inhibitor who developed a mild cough may be more likely to be switched to another antihypertensive than a patient who was on a beta-blocker. There is no evidence that this occurred. Otherwise, this was a well-designed investigation.

Outcomes measured Twenty-one clinical end points were analyzed. Death from all causes, death due to diabetes, and the development of any macrovascular or microvascular complications were the primary outcomes evaluated. The effect of the drugs on other outcomes also was evaluated, including myocardial infarction, stroke, amputation or death from peripheral vascular disease, retinopathy, and renal failure.

Results Of the 4297 subjects recruited into the UKPDS, 1,544 (36%) had hypertension and were eligible for this study. After exclusions, 758 were randomly assigned to receive tight control of their blood pressure. Of those, 400 were randomly assigned to receive captopril, and 358 received atenolol. The 2 groups were similar m mean age (56 years), race, sex, and the presence of cardiovascular risk factors.

After an average of 9 years of monitoring, captopril and atenolol were equally effective in achieving tight blood pressure control. A similar percentage of patients in both groups (27% in the captopril group vs 31% in the atenolol group) required at least 3 antihypertensive agents to achieve a blood pressure of [is less than] 150/85 mm Hg. After 4 years of treatment, significantly more patients in the atenolol group were noncompliant because of side effects (eg, impaired peripheral circulation and bronchospasm) as compared with the captopril group (35% vs 22%, P [is less than] .0001).

The drugs were equally effective in preventing the outcomes measured. The incidence of macrovascular and microvascular complications, death from diabetes, and all-cause mortality were similar in both groups. There was no difference in the development of any of the clinical end points measured, including myocardial infarction, stroke, heart failure, angina, retinopathy, and renal failure. In terms of surrogate measures, more patients taking atenolol required art additional blood-glucose-lowering agent to achieve control as compared with those receiving captopril (66% vs 53%, P = .0015), and they gained more weight (3.4 kg vs 1.6 kg, P = .02). The incidence of hypoglycemia or hyperlipidemia was similar between the 2 groups.

Recommendations for clinical practice When choosing an antihypertensive for a patient with type 2 diabetes, captopril and atenolol are equally effective as first-line therapy in controlling hypertension and preventing diabetes-related complications. However, successfully achieving tight control ([is less than] 150/85 mg Hg) requires diligence from the physician and the patient. Up to a third of these patients will require at least 3 antihypertensives, and nearly a third will be noncompliant with the initial antihypertensive because of side effects.