Hierarchical modeling of blood pressure determinants and outcomes following valsartan treatment in hypertensive patients with known comorbidities: pooled analysis of six prospective real-world studies including 11,999 patients

Abstract

Aims

Six prospective real-world studies of antihypertensive treatment with valsartan-centric regimens were pooled to: (1) examine the effectiveness of ∼90 days of second- or later-line valsartan treatment in hypertensive patients with known comorbidities; and (2) identify physician- and patient-related determinants associated with systolic (SBP) and diastolic blood pressure (DBP) outcomes in these patients.

Methods and materials

A pooled analysis was performed of an evaluable sample of 11,999 hypertensive patients with known comorbidities treated ∼90 days with valsartan-centric regimens. We applied hierarchical linear and logistic regression models to identify determinants of blood pressure (BP) outcomes and a potential physician class effect.

Results

Valsartan regimens resulted in mean (SD) SBP and DBP reductions of 18.0 (15.8) mmHg and 9.5 (10.1) mmHg, respectively, at ∼90 days, yielding SBP, DBP and combined SBP/DBP control rates of 44.0%, 67.2% and 39.3%, respectively. About a quarter of the variance in 90 day BP values was attributable to a physician class effect. BP outcomes declined with physicians’ increasing years in practice and being male. At the patient level, BP outcomes declined with SBP and DBP at diagnosis; diabetes; higher cholesterol and BMI; lower valsartan and hydrochlorothiazide (HCTZ) doses; and concomitant anti-hypertensives. Older age was associated with improved DBP. A proxy of physician vigilance, cardiovascular disease history, was associated with improved BP outcomes, as were patient adherence and higher doses of valsartan in combination with HCTZ.

Conclusions

Valsartan-centric regimens have significant BP lowering benefits in this pooled sample of patients with known comorbidities. Many observed determinants of BP outcomes are modifiable or manageable.

Keywords:

• Angiotensin II receptor blockers
• antihypertensive agents
• blood pressure
• epidemiologic studies
• hypertension
• logistic models
• medication adherence
• valsartan
• determinant factors

Transparency

Declaration of funding

The six studies in this pooled analysis were sponsored by Novartis Pharma (Belgium) through research contracts to Matrix45. Statistical analysis and manuscript development were done independently from the sponsor and without funding at Matrix45 and the University of Arizona. Novartis had right of review and comment. Authors employed by Novartis refrained from undue influence. Any issues related to results or manuscript were addressed by the external authors.

Declaration of financial/other relationships

H.B. and S.V. have disclosed that they are employees of Novartis and own equity in Novartis. I.A., K.D., K.M. and S.V. have disclosed that they are employees of Novartis and own equity in Novartis. I.A., K.D. and K.M. have disclosed that they are employees of Matrix45. By company policy, they cannot hold equity in sponsor and client companies, perform services, or receive compensation independently from sponsor and client organizations. No potential conflict of interest was reported by the remaining authors. Authors employed by the sponsor refrained from undue influence. Any issues related to results or manuscript were addressed by the external authors.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Study concept and design: I.A., H.B., K.M., S.V.; data acquisition and management: H.B., K.D., K.M.; statistical analysis: I.A., N.A., K.D., K.M.; tabulation of results: I.A., N.A., K.D., D.H., K.M., D.S., Y.V.C., L.V.; quality control: N.A., K.M.; interpretation of results: all authors; manuscript writing: I.A., N.A., K.D., D.H., D.S.; critical review of manuscript for scientific content: all authors; all authors met the ICMJE criteria for authorship (in alphabetical order).

Acknowledgements

D.H. is now at Ro’ya Tholathiyat Al Aba’d (Amman, Jordan). D.S. is now at Genentech (South San Francisco, CA, USA). Y.V.C. is now in the House of Representatives of Belgium (Brussel, Belgium) and the Universiteit Antwerpen (Antwerpen, Belgium). L.V. is now at the University of Colorado – Denver.