Real-world effectiveness of valsartan on hypertension and total cardiovascular risk: review and implications of a translational research program

Abstract

The pharmacological efficacy of various monotherapy, single pill, and combination therapies of the angiotensin II receptor blocker valsartan have been established, mainly through randomized controlled trials that used similar methodological and statistical platforms and thus enabled synthesis of evidence. The real world effectiveness of valsartan has been studied extensively, but the relative lack of scientific and technical congruence of these studies render synthesis virtually impossible. To date, all have focused on blood pressure outcomes, despite evidence-based calls to grade antihypertensive treatment to patients’ total cardiovascular risk. We review a T3 translational research program of seven studies involving valsartan monotherapy as well as single and separate pill combinations, and the determinants and effect on blood pressure and total cardiovascular risk outcomes. All seven studies examined not only the impact of valsartan-based regimens on blood pressure values and control, but also, within a statistical hierarchical approach, the physician- and patient-related determinants of these blood pressure outcomes. Two studies also investigated the determinants and outcomes of valsartan-based treatment on total cardiovascular risk – among the first studies to use this risk coefficient as an outcome rather than only a determinant. These seven studies included a total of 19,533 patients, contributed by 3434 physician-investigators in Belgium – a country particularly well-suited for observational effectiveness studies because of demographics and epidemiology. Each study used the same methodological and statistical platform. We summarize the impact of various valsartan regimens on such outcomes as blood pressure values and control, change in total cardiovascular risk, and reduction in risk by at least one category. We also review the results of statistical multilevel and logistic modeling of physician- and patient-related determinants on these outcomes, including the proportion of variance attributable to a physician class effect before patients enter the equation. In its different formulations, valsartan has major real-world benefits in lowering blood pressure and total cardiovascular risk within a 90-day period. It is essential to understand the physician- and patient-related determinants of blood pressure and total cardiovascular risk outcomes associated with valsartan treatment. Antihypertensive research should expand its historical focus on lowering blood pressure with an emphasis on lowering total cardiovascular research.

Keywords:

• valsartan
• angiotensin II receptor blocker
• hypertension
• total cardiovascular risk
• effectiveness
• pharmaco-epidemiology

Acknowledgements

The seven studies reviewed in this paper were sponsored by Novartis Pharma.

The authors thank Sandy Kramer and Jennifer Martin, Arizona Health Sciences Library, for their expert assistance with the literature search.

Independence of Writing Committee

The Writing Committee consisted of Ivo Abraham, Karen MacDonald, and Christopher Lee. All content decisions were made by the external authors. Sponsor had right of review and comment; co-authors affiliated with sponsor refrained from undue influence.

Disclosure

Stefaan Vancayzeele, Christine Hermans, Ann Aerts, and Heidi Brié are employees of Novartis Pharma. Ivo Abraham, Karen MacDonald, and Christopher Lee are employees of Matrix45. By company policy, employees are prohibited from owning equity in client organizations (except through mutual funds or other independently administered collective investment instruments) or contracting independently with client organizations. Matrix45 provides similar services to those described in this article to other biopharmaceutical companies on a non-exclusivity basis.

No services were provided by writers or editors employed by a medical education and communication company.