Effectiveness of amlodipine-valsartan single-pill combinations: hierarchical modeling of blood pressure and total cardiovascular disease risk outcomes (the EXCELLENT study).

Background: Both patient- and physician-related factors have been shown to explain variability in the outcomes of antihypertensive treatment. Total cardiovascular risk (TCVR) is increasingly used as a determinant of treatment effectiveness but has also been proposed as a treatment outcome. To our knowledge, no studies have reported how antihypertensive treatment impacts blood pressure and TCVR outcomes.

Objective: To examine in patients treated with a regimen including single-pill combinations (SPCs) of amlodipine/valsartan (1) blood pressure (BP) reduction and control, total cardiovascular risk (TCVR) change, and TCVR reduction of 1 class or more; (2) hierarchical patient- and physician-level determinants of these outcomes; and (3) predictors of uncontrolled BP and improved TCVR classification.

Methods: A prospective (90 days), multicenter, multilevel pharmacoepidemiologic study was conducted in 3546 patients with hypertension treated with SPC amlodipine/valsartan by 698 general practitioners. Statistical analysis included hierarchical linear and logistic modeling of BP and TCVR outcomes.

Results: Mean (SD) systolic BP (SBP) reductions were 20.1 (15.5) mm Hg and diastolic BP (DBP) reductions were 9.8 (10.3) mm Hg, with higher reductions among high-risk patients. SBP, DBP, and SBP/DBP control rates were 33.3%, 45.3%, and 25.5%, respectively, with lower rates among high-risk patients. Mean TCVR improvement was a reduction of 0.73 (0.96) classes (-4 [best] to +4 [worst]), with higher reductions for high-risk patients; 58.2% of patients achieved a TCVR reduction of 1 or more classes, with lower percentages for high-risk patients. Twenty-two percent of systolic variability and 26% of diastolic variability in 90-day BP values were attributable to a physician class effect, as was 16% of TCVR change.

Conclusions: Regimens that include SPC amlodipine/valsartan formulations are effective in reducing BP and TCVR in a real-world observational setting. Hierarchical modeling identified patient- and physician-related determinants of BP values and TCVR change, as well as independent predictors of uncontrolled BP and reduced TCVR. TCVR is a scientifically feasible and clinically relevant effectiveness outcome of antihypertensive treatment.