Tight Blood Pressure Control In Type 2 Diabetes

Journal of Family Practice, Dec, 1998 by Tom Wroth, Warren Newton

UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317:703-13.

Clinical question Does tight blood pressure control in patients with type 2 diabetes reduce morbidity and mortality?

Background The importance of aggressive blood pressure lowering in patients with type 2 diabetes is controversial. The purpose of this study was to determine whether tight blood pressure control prevented macrovascular and microvascular complications in these patients.

Population studied As part of a large prospective trial evaluating the treatment of type 2 diabetes, 1544 patients with newly diagnosed disease who also had hypertension were identified in British general practices. Hypertension was defined as systolic blood pressure (SBP) [is greater than] 160 mm Hg or diastolic blood pressure (DBP) [is greater than] 90 mm Hg, or treated hypertension with SBP [is greater than] 150 mm Hg or DBP [is greater than] 85 mm Hg. Patients were excluded if they had a clinical requirement for strict blood pressure control (eg, heart failure) or a need for beta-blockade (angina or recent myocardial infarction), or conversely, if they had a contraindication for beta-blocker use. The average age was 56 years, 56% were men, average Hb [A.sub.1c] level was 6.9%, and 8% were of African descent. The study population seems similar to patients seen by family practitioners.

Study design and validity This was a prospective randomized controlled trial. Patients were randomized to tight control ([is less than] 150/ [is less than] 85 mm Hg) and either captopril or atenolol, or less-tight control ([is less than] 200/[is less than] 105 mm Hg) with usual care but initially avoiding the study drugs. The target for systolic pressure was decreased to 180 mm Hg 5 years after the study began. Patients were evaluated every 3 to 4 months, and theft medications were adjusted according to a protocol. For patients not meeting targets, and for those in the less-tight control group, other agents were added in the following order: furosemide, slow-release nifedipine, methyldopa, and prazosin. Outcomes were assessed blindly, and analysis was by intention to treat.

Overall, the study design was strong. Weaknesses included not using beta-blockers or angiotensin-converting enzyme (ACE) inhibitors in the less-tight control group, which raised the issue of whether the results were because of tight control or the use of atenolol or captopril; and using agents, such as furosemide, that are not commonly used for this indication in the United States and have weaker evidence of effectiveness.

Outcomes measured The primary end points were time-to-occurrence of clinical outcomes related to diabetes (myocardial infarction, angina, sudden death, stroke, congestive heart failure, renal failure, amputation, retinopathy, and fatal hypoglycemia or hyperglycemia); death related to diabetes; and death of any cause. Cost-effectiveness was reported in another study; patient satisfaction and quality of life were not reported.

Results The groups were similar in terms of starting blood pressure, age, sex, and Hb [A.sub.1c] levels. Follow-up was excellent, with data available for 96% of participants at 8.4 years. Mean blood pressure for the tight control and the less-tight control group was 144/82 mm Hg and 154/87 mm Hg, respectively. Twenty-nine percent of the patients in the tight control group required 3 or more agents to achieve target blood pressure.

Tight control decreased the risk of diabetes-related end points by 10% (34% vs 44%; P = .0046; number needed to treat [NNT] = 11) with a 5% reduction in diabetes-related deaths (11% vs 16%; P = .019; NNT = 20). The reduction in all-cause mortality was not statistically significant. There was also an impressive reduction in the incidence of microvascular disease (9% vs 14%; P = .0092; NNT = 21) mostly because of a decrease in retinopathy. Although there was a trend for a decrease in nephropathy, it was not statistically significant.

Recommendations for clinical practice This study provides good evidence that tight blood pressure control starting with atenolol or captopril improves outcomes in people with type 2 diabetes. The results should generalize to other beta-blockers and ACE inhibitors, but the data do not address the impact of tight control with other agents or the contributions of specific drugs. More information about whether treatment of African Americans should differ would also be valuable.

It is intriguing that tight blood pressure control was more effective than tight blood glucose control in decreasing diabetes-related end points (renin release rate = 24% w 12%).[1] When combined with recent work on smoking cessation, aspirin, and lipid-lowering in people with type 2 diabetes, these data support physicians' shift away from an exclusive focus on tight control of blood glucose to more aggressive treatment of other cardiovascular risk factors.