Effect of Baseline and Changes in Systolic Blood Pressure Over Time on the Effectiveness of Valsartan in the Valsartan Heart Failure Trial

Abstract

Background-Low systolic blood pressure (SBP) is a risk factor for adverse outcomes in patients with heart failure (HF).Valsartan improved morbidity rates in the Valsartan Heart Failure Trial (Val-HeFT) despite a reduction in SBP. The aim of the present study was to investigate the relationship between the SBP-lowering effects of valsartan and its cardiovascular protective effects in this population. Methods and Results-Baseline measurements and changes in SBP at 4 months were related to mortality and morbidity rates.The effects of valsartan on these end points were compared in quartiles of baseline SBP with multivariable Cox proportional hazards regression models that included a test for interaction between the effects of valsartan treatment and baseline SBP and examined the effects of changes in SBP on the valsartan effect. The meanϮSD baseline SBP in all patients (nϭ5010) Key Words: heart failure Ⅲ blood pressure Ⅲ clinical trial Ⅲ valsartan Ⅲ outcomes H igh blood pressure increases the risk of death in the general population, 1,2 and hypertension is the most important population-attributable risk factor for the development of heart failure (HF). 3,4 The benefits of treating hypertension on risks of major cardiovascular events are well established in the absence of systolic HF, and effective lowering of blood pressure is associated with an Ϸ50% reduction in the incidence of HF. 5,6 Once HF develops, however, lower blood pressure becomes a risk factor for increased mortality and morbidity rates both in acute decompensated 7,8 and chronic HF. 9 -11 The risk associated with elevated blood pressure in patients with systolic dysfunction has not been established. Vasodilators used in the treatment of hypertension, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and a combination of hydralazine and isosorbide, are also effective in reducing mortality and morbidity rates in patients with HF. [12][13][14][15][16][17] Whether the beneficial effects of these medications on morbidity and mortality rates in patients with HF are modified by initially low or drops in blood pressure is an important clinical issue. Clinical Perspective p 42The present study is a secondary analysis of the Valsartan Heart Failure Trial (Val-HeFT) database to study the effects of baseline blood pressure and changes in blood pressure over time on the effectiveness of treatment with valsartan on morbidity and mortality in patients with moderate to severe HF. First, we sought to confirm that both lower baseline systolic blood pressure (SBP) and a decrease in SBP over time were independently associated with an increased risk of morbidity and mortality. The interaction between the effects of valsartan and baseline SBP was then examined, controlling for several other known prognostic variables. Finally, to determine whether adjusting for any potentially deleterious drops in SBP during treatment would enhance the apparent beneficial effects of valsartan, we examined how controlling for changes in SBP affected the benef...

Early and Late Effects of High- Versus Low-Dose Angiotensin Receptor Blockade on Renal Function and Outcomes in Patients With Chronic Heart Failure

“…These findings may be somewhat analogous to effect of valsartan on blood pressure as seen in Val-HeFT (35 …”

Impact of systolic blood pressure on the safety and tolerability of initiating and up‐titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study

“…suggested that the clinical benefits of add‐on neurohormonal blockade may be balanced or even neutralized by risk for hypotension . However, reports from large HF trials, such as COPERNICUS, CHARM, A‐HeFT and Val‐HeFT, suggest that dosing and trial completion are limited to a greater extent by the severity of HF than by drug intolerance to HF therapy per se , as patients receiving placebo were almost as likely to discontinue as patients receiving the active study treatment, regardless of SBP. Furthermore, in line with these and more recent trial data, practical guidance for the management of HF patients with low SBP emphasizes the importance of using guideline‐directed therapies despite low SBP as the symptoms of hypotension may resolve as HF improves …”

Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association

“…However, the beneficial effects of the HF medications are usually independent of the baseline BP or changes in BP and do not vary according to baseline BP or reductions in SBP levels. [60][61][62] Medication Choices for the Treatment of Hypertension in Patients With HF Currently, there are no randomized, large-scale trials comparing the effectiveness of different antihypertensive medications targeting optimal treatment of BP solely in patients with hypertension and established HF. Thus, most evidence comes from hypertension clinical trials that have not excluded patients with a history of HF.…”