Hypertension treatment reduced long-term mortality, but intensive glucose control didn't

Hypertension treatment with perindopril-indapamide for 4.5 years had a long-lasting impact on mortality in patients with type 2 diabetes, but intensive glucose control was not associated with any significant benefit, a study found.

Researchers conducted a 6-year post-trial follow-up (10 years total, including the original study timeframe) among more than 8,000 surviving patients from the ADVANCE study who had previously been randomly assigned to perindopril (4 mg) and indapamide (1.25 mg) or placebo and either a gliclazide-based intensive glucose control regimen (HbA1c target of 6.5%) or standard glucose control. Primary end points included death from any cause and from major macrovascular events, which were a composite of nonfatal myocardial infarction, nonfatal stroke, or death from any cardiovascular cause. Secondary outcomes included death from cardiovascular causes, major clinical microvascular events, diabetes-related retinal photocoagulation or diabetes-related blindness, or major hypoglycemia.

Results appeared online Sept. 19 at the New England Journal of Medicine.

Although the groups had no significant differences in blood pressure or blood sugar by the first visit after the conclusion of the trial, the patients assigned to perindopril-indapamide therapy had a significantly lower risk for all-cause mortality (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P=0.03) that lasted to the end of the study. The reduction was consistent with that group's lower all-cause mortality during the trial (HR, 0.86; 95% CI, 0.75 to 0.98; P=0.03). The hypertension treatment group also maintained a reduced risk of death from cardiovascular causes in follow-up (HR, 0.88; 95% CI, 0.77 to 0.99; P=0.04), although it was attenuated from the in-trial reduction in risk (HR, 0.82; 95% CI, 0.68 to 0.98; P=0.03).

There were no cumulative benefits for any other secondary outcome, including major clinical microvascular events, and no follow-up benefits were found from the intensive glucose control. While there was a significant cumulative benefit with respect to end-stage renal disease (HR=0.54; 95% CI, 0.34 to 0.85; P=0.007), the authors noted that there were a small number of overall events and cautioned about interpreting the benefits when considering this end point.

The authors noted that their findings differ from other recent research into the long-term effects of intensive glucose control, and they speculated that the lack of benefit might be due to the fact that their patients had more long-standing disease, the lack of difference in actual HbA1c levels between groups, or insufficiently long follow-up to show benefit.