BACKGROUND: Strong evidence exists that the greater the blood pressure reduction in patients with type 2 diabetes, the greater the clinical benefit in reducing significant cardiovascular events and death.1 It is not known whether these benefits are actually due to the lowering of blood pressure or if there is a drug class effect, particularly among ACEIs.
POPULATION STUDIED: The average age of participants in the 4 studies was 58 years, and 60% were men. The study settings (primary care or referral) were not reported. Baseline blood pressures ranged from 155 to 170 systolic and 93 to 98 diastolic. The duration of diabetes was 8.5 to 10.7 years in 2 studies, 2.7 years in 1 study, and was not reported in 1 study.
STUDY DESIGN AND VALIDITY: This was a meta-analysis. The authors performed a MEDLINE search for studies pertaining to ACEIs, diabetes, and hypertension but did not search any other databases such as the Cochrane Controlled Trials Register. Studies were included if they were randomized controlled trials of patients with type 2 diabetes that evaluated an ACEI versus another antihypertensive medication with a minimum follow-up of 2 years. There was no indication whether retrieved studies were reviewed independently by 2 or more authors for inclusion. Tests for heterogeneity were appropriately applied to assure that only data from similar studies were combined. A fixed effects model, which assumes homogeneity, was used to combine data.
OUTCOMES MEASURED: The outcomes measured were acute myocardial infarction (AMI), stroke, combined cardiovascular events, and all-cause mortality. The combined cardiovascular events varied depending on the particular trial and could include cardiovascular death, fatal and nonfatal MI, fatal and nonfatal stroke, angina, congestive heart failure, and pulmonary infarction.
RESULTS: The initial search identified 195 articles of which 4 studies with a total of 2180 patients met the inclusion criteria. After applying tests for heterogeneity, only data from 3 trials (which studied enalopril vs nisoldipine, captopril vs diuretic/b-blocker, and fosinopril vs amlodipine) were used in the meta-analysis. In one of these trials (captopril vs diuretic/b-blocker), the number of events in persons with diabetes was not reported; it was therefore estimated by the authors of this review. This is a limitation of this meta-analysis. The relative risk calculations for these 3 studies showed that using ACEIs versus other antihypertensives lowered the number of AMIs (summary risk ratio [RR]=0.37; 95% confidence interval [CI], 0.24-0.57), had no affect on the incidence of stroke (RR=0.76; 95% CI, 0.48-1.22), lowered the number of combined cardiovascular events (RR=0.49; 95% CI, 0.36-0.67), and lowered overall cardiovascular mortality (RR=0.57; 95% CI, 0.38-0.87). On the basis of these data, to prevent an additional AMI, cardiovascular event, or death one would have to treat 17, 13, and 40 patients respectively with an ACEI instead of another agent for approximately 4.5 years. The study excluded from the meta-analysis compared outcomes in patients taking an ACEI versus atenolol and found no statistically significant differences between the groups for the 4 clinical outcomes.1
Lowering blood pressure in patients with type 2 diabetes who have hypertension has clear benefits in terms of reducing the number of AMIs, cardiovascular events, and deaths. Although the data presented in this meta-analysis suggest that ACEIs may be more effective than calcium-channel blockers or the combination of a diuretic and a b-blocker, they are not conclusive. In particular, atenolol may have a similar benefit to ACEIs. The decision to use ACEIs in people with diabetes who have hypertension should continue to be made based on patient-specific clinical factors, their effectiveness in lowering blood pressure, and current evidence of benefit in patients with comorbid conditions (eg, microalbuminuria and congestive heart failure).