Intensive Blood Pressure Lowering in Patients With and Without Type 2 Diabetes

Pooled analysis from two randomized trials on intensive blood pressure lowering shows significant differences in effects on two groups.

The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) study did not find a significant beneficial effect of intensive systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure Intervention Trial (SPRINT) did find a significant beneficial effect in patients without T2DM. The objective of this analysis was to assess the effect of both T2DM and baseline cardiovascular disease (CVD) risk on the treatment effect of intensive blood pressure lowering.

The individual patient data from both the ACCORD-BP and SPRINT studies were pooled and followed up. Then both studies randomized hypertensive patients to an SBP target of <120 mmHg or a target of <140 mmHg. The composite primary end point consisted of unstable angina, myocardial infarction, acute heart failure, stroke, and cardiovascular death. The interaction between intensive blood pressure lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox proportional hazards models.

The cohort consisted of 14,094 patients with mean age 66 ± 8.9 years and mean baseline SBP 139.5 ± 15.6 mmHg; 33.6% had T2DM. The hazard ratio for the primary composite endpoint was 0.82 (95% CI 0.73–0.93) (P = 0.0017). The interaction between intensive blood pressure lowering and T2DM was nonsignificant (P = 0.13). The 10-year cardiovascular risk was higher in primary prevention patients with T2DM, but risk did not interact with the treatment effect (P = 0.84).

The incidence of the primary end point in the pooled cohort was 7.3% during a median follow-up of 3.26 years. The event rate was 8.0% in the intensive treatment group vs. 6.6% in the standard treatment group. The hazard ratio for the primary composite endpoint was 0.82 (95% CI 0.73–0.3) (P = 0.002). The individual secondary endpoints were not significantly different between the treatment groups, except acute heart failure events. Cardiovascular mortality and all-cause mortality were non-significantly lower. The post hoc calculated power in the pooled cohort for the primary composite endpoint was 88.9%. The event rate in patients with T2DM was higher than in non-T2DM patients (9.8% vs. 6.0%, P, 0.001). In patients with T2DM, the event rate was lower in the intensive group, 10.3% vs. 9.4%, but this difference was nonsignificant (P = 0.32). The event rate in patients without T2DM was also lower in the intensive group: 6.8% vs. 5.2% (P, 0.001). Also, the model fit did not improve when an interaction term was forced in the Cox model (AIC 19,205 vs. 19,205, P = 0.13) indicating that there is no evidence that intensive blood pressure lowering to 120 mmHg has a different relative effect in patients with T2DM compared with patients without T2DM. The post hoc calculated power in ACCORD-BP using the SPRINT composite end point was 17.5% vs. 91.6% in SPRINT at 3.26 years median follow-up duration. With the observed treatment effect in ACCORD-BP, 50,000 patients would be needed to reach 90% power.

At baseline, the two studies differed significantly except for baseline SBP, smoking. and aspirin use. The distribution of 10-year risk score of CVD was different in the two studies. Patients in the pooled cohort had a mean age of 66 6 years, and 39.7% were female. The randomization remained intact when the baseline characteristics were judged both by absolute numbers and statistically. The mean SBP at baseline was 139.5mmHg and the mean diastolic blood pressure was 77.4mmHg. In the pooled cohort, 33.6% of patients had T2DM and the median 10-year risk of cardiovascular disease was 25%.

From the results, it was concluded that, in this pooled cohort, intensive blood pressure lowering to an SBP target,120 mmHg, reduces the cardiovascular events in patients with an increased cardiovascular risk and an SBP between 130 mmHg and 180 mmHg. Cardiovascular mortality and all-cause mortality were not significantly different. These analyses do not provide any evidence for a differential effect of intensive blood pressure lowering in patients with T2DM or a higher 10-year risk cardiovascular disease.

Practice Pearls:

• Cardiovascular mortality and all-cause mortality were not significantly different.
• Intensive blood pressure lowering to an SBP target, 120 mmHg, reduces the cardiovascular events in patients with an increased cardiovascular risk and an SBP between 130 mmHg and 180 mmHg.
• Intensive blood pressure lowering may have a similar favorable effect and appears to decrease cardiovascular events in both patients with and patients without T2DM.

Diabetes Care 2017 Dec; dc171722. https://doi.org/10.2337/dc17-1722