Influence of Blood Pressure on the Effectiveness of a Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine in the African-American Heart Failure Trial

Anand, Inder S.; Tam, S. William; Rector, Thomas S.; Taylor, Anne L.; Sabolinski, Michael L.; Archambault, W. Tad; Adams, Kirkwood F.; Olukotun, Adeoye Y.; Worcel, Manuel; Cohn, Jay N.

doi:10.1016/j.jacc.2006.04.109

Cited by 60 publications

(44 citation statements)

References 17 publications

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“…Vasodilators such as sodium nitroprusside reverse the functional abnormalities acutely by improving stroke volume and may increase blood pressure. 10,20,21 Thus, the vasodilatory effects of valsartan might have lowered arterial impedance in patients with the lowest SBP who would be expected to have the highest impedance, thereby increasing the cardiac output and maintaining blood pressure. Over the long term, valsartan use was associated with an improvement in LV ejection fraction 22 and a decrease in the levels of several neurohormones, including brain natriuretic peptide, norepinephrine, and aldosterone.…”

Section: Discussionmentioning

confidence: 99%

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

Anand

Rector

Kuskowski

et al. 2008

Circ: Heart Failure

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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...

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Section: Discussionmentioning

confidence: 99%

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

Anand

Rector

Kuskowski

et al. 2008

Circ: Heart Failure

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“…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.…”

Section: Iia C 8 71mentioning

confidence: 99%

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

Bozkurt¹,

Aguilar²,

Deswal³

et al. 2016

Circulation

366

220

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CLINICAL STATEMENTS AND GUIDELINESfailed to show a significant reduction of SBP in patients with resistant hypertension. 81 Other strategies such as targeting excessive sympathetic nerve activity by carotid body denervation are awaiting clinical validation in the hypertension and HF populations. Drugs to Avoid in Patients With HFSeveral classes of drugs should be avoided in patients with HFrEF with a history of hypertension. Because of their negative inotropic properties and the increased likelihood of worsening HF symptoms, the nondihydropyridine calcium channel blockers such as diltiazem and verapamil should be avoided. 8 The dihydropyridine calcium channel blocker amlodipine appeared to be safe in patients with severe HFrEF in the PRAISE trial (Prospective Randomized Amlodipine Survival Evaluation), 82 as was felodipine. 73 In the current 2013 HF guidelines, most calcium channelblocking drugs except amlodipine are not recommended. 8Although clonidine is an effective antihypertensive agent, a similar centrally acting drug, moxonidine, was associated with increased mortality in patients with HF; thus, centrally acting norepinephrine-depleting agents may need to be avoided or used with caution in patients with HFrEF. 83In the ALLHAT trial, the α-blocker doxazosin arm of the trial was discontinued because of a 2-fold increase in the risk of developing HF compared with chlorthalidone treatment. 45 Although the ALLHAT study excluded patients with established HF and there are caveats about extrapolating these data to the management of hypertension in patients with established HF, the safety and efficacy of α-blockers in the management of patients with HF with hypertension are currently unclear. Potent direct-acting vasodilators such as minoxidil should also be avoided because of their renin-related salt and fluid-retaining effects. Nonsteroidal anti-inflammatory agents should be used with caution in these patients, given their effects on BP, volume status, and renal function. Treatment of Hypertension in Patients With HF With Preserved LVEFMost patients with HF and preserved LVEF (HFpEF), especially elderly women, have hypertension. A significant proportion of these patients also have evidence of LV hypertrophy, and some may have atrial dilatation, cardiac enlargement, and wall motion abnormalities without LV systolic dysfunction. Patients with HFpEF may respond particularly well to the treatment of hypertension with regression of hypertrophy 84 and improvement in filling pressures. 84,85 Most patients with HFpEF require treatment with cardiac medications for the comorbidities of hypertension, diabetes mellitus, coronary artery disease, and atrial fibrillation. The 2013 HF guidelines suggest that the use of β-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is reasonable to control BP in patients with HFpEF. 8 The use of ARBs might also be considered to decrease hospitalizations for patients with HFpEF. recommendations Harmonized With Existing Guidelines for the recognition and Treatment of pa...

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“…13 Despite their potential hemodynamic effects, certain successful drugs actually improve blood pressure profile over time secondary to improving cardiac mechanics and function. 35 Many successful HFrEF vasoactive agents may exert heterogeneous blood pressure-lowering effects, such that deleterious hypotensive effects may be limited to select clinical subgroups including patients, for example, those with advanced age, coronary artery disease, renal dysfunction, and poor functional status. Although omapatrilat did not reduce mortality or hospitalization risk compared with enalapril in the overall Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) trial, post hoc analysis supported clinical benefit of omapatrilat in the subgroup with higher blood pressure.…”

Section: Success Of Established Therapiesmentioning

confidence: 99%

Contemporary Drug Development in Heart Failure

Vaduganathan

Butler

Pitt

et al. 2015

Circ: Heart Failure

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Influence of Blood Pressure on the Effectiveness of a Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine in the African-American Heart Failure Trial

Cited by 60 publications

References 17 publications

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

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

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

Contemporary Drug Development in Heart Failure

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