The JNC 7 approach compared to conventional treatment in diabetic patients with hypertension: a double-blind trial of initial monotherapy vs. combination therapy

Abstract

The JNC 7 states that persons with blood pressure (BP) more than 20/10 mm Hg above goal should be started on combination drug therapy. This criterion includes patients with BP >160/100 mm Hg and diabetics with hypertension. The goal BP for persons with diabetes mellitus is <130/80 mm Hg. A randomized, double-blind trial force titrated initial combination therapy utilizing an angiotensin receptor blocker (ARB) combination (losartan/hydrochlorothiazide [LOS/HCTZ]) compared with an angiotensin-converting enzyme (ACE) inhibitor (ramipril), for 8 weeks, and tested the hypothesis that combination therapy is more likely to achieve goal BP vs. monotherapy. At 4 weeks, 30.5% of LOS/HCTZ and 14.4% of ramipril recipients achieved goal diastolic BP (p<0.001). More participants achieved goal systolic BP in the ARB/HCTZ group at 4 weeks (29.8% vs. 14.4%; p<0.001). At 4 weeks, mean diastolic BP had decreased 10.2+/-7.4 mm Hg in the LOS/HCTZ group compared with 6.4+/-6.8 mm Hg in the ramipril group (p<0.001), and systolic BP had fallen 15.4+/-13.1 mm Hg in the ARB/HCTZ compared with 9.2+/-10.2 mm Hg in the ACE-inhibitor group (p<0.001). Significant differences favoring the combination were also noted at 8 weeks. Drug-related adverse experiences were 10.3% for the combination compared with 12.7% for the monotherapy group. Initial combination therapy with an ARB/HCTZ was more effective than ACE-inhibitor monotherapy in achieving BP goals in participants with diabetes with no significant differences in the incidence of adverse experiences. These observations confirm other studies of combination therapies, such as b blocker/diuretic, ACE inhibitor/diuretic, or ACE inhibitor/calcium channel blocker. The use of two medications will achieve goal BP in more patients than monotherapy. This observation is important in treatment of high-risk patients with diabetes.

Figures

Figure 1

Study design. PBO=placebo; LOS/HCTZ= losartan/hydrochlorothiazide; V=visit; dashed line=sham titration; *patients were stratified based on blood pressure (sitting diastolic blood pressure 90–109 mm Hg or sitting diastolic blood pressure 110–120 mm Hg); †variable taper/washout period of a minimum of 7 days off all hypertension medications before baseline (V2=Week 2) with possible early randomization at V3

Figure 2

Percentages of participants attaining goals of therapy for sitting diastolic blood pressure (SiDBP) and sitting systolic blood pressure (SiSBP). LOS/HCTZ=losartan/hydrochlorothiazide; *the primary efficacy measure occurred at 4 weeks.

Figure 3

Changes in mean systolic and diastolic blood pressure at study randomization (Week 0) and each week of titration (ramipril Weeks 2, 4, and 6, losartan [LOS]/hydrochlorothiazide [HCTZ] Week 4). LOS/HCTZ sham‐titrated at Weeks 2 and 6. Error bars represent 95% confidence intervals.