Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure

Gheorghiade, Mihai; Böhm, Michael; Greene, Stephen J.; Fonarow, Gregg C.; Lewis, Eldrin F.; Zannad, Faı̈ez; Solomon, Scott D.; Baschiera, Fabio; Botha, Jaco; Hua, Tsushung A.; Gimpelewicz, Claudio; Jaumont, Xavier; Lesogor, Anastasia; Maggioni, Aldo P.; Coordinators,

doi:10.1001/jama.2013.1954

Cited by 316 publications

(245 citation statements)

References 30 publications

Supporting

Mentioning

220

Contrasting

Unclassified

Order By: Relevance

“…40 However, therapeutic combination of aliskiren with either an ACE inhibitor or an ARB results in a greater frequency of adverse events, fails to improve left ventricular remodeling after myocardial infarction, fails to reduce cardiovascular and renal events in high-risk patients with type 2 diabetes mellitus, and fails to reduce postdischarge mortality and heart failure readmissions in hospitalized patients with heart failure. [41][42][43] Similar increases in adverse effects were observed with combinations of ACE inhibitors and ARBs. 44,45 The adverse effects associated with combinations of renin-angiotensin system inhibitors are likely due to excessive blockade of AT 1 receptor-mediated effects.…”

Section: Discussionmentioning

confidence: 66%

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

2014

View full text Add to dashboard Cite

Abstract-Angiotensin-converting enzyme inhibitors and angiotensin AT 1 receptor blockers reduce myocardial ischemiareperfusion injury via bradykinin B 2 receptor-and angiotensin AT 2 receptor-mediated mechanisms. The renin inhibitor aliskiren increases cardiac tissue kallikrein and bradykinin levels. In the present study, we investigated the effect of aliskiren on myocardial ischemia-reperfusion injury and the roles of B 2 and AT 2 receptors in this effect. Female SpragueDawley rats were treated with aliskiren (10 mg/kg per day) and valsartan (30 mg/kg per day), alone or in combination, together with the B 2 receptor antagonist icatibant (0.5 mg/kg per day) or the AT 2 receptor antagonist PD123319 (30 mg/ kg per day), for 4 weeks before myocardial ischemia-reperfusion injury. Aliskiren increased cardiac bradykinin levels and attenuated valsartan-induced increases in plasma angiotensin II levels. In vehicle-treated rats, myocardial infarct size (% area at risk, mean±SEM, n=7-13) was 43±3%. This was reduced to a similar extent by aliskiren, valsartan, and their combination to 24±3%, 25±3%, and 22±2%, respectively. Icatibant reversed the cardioprotective effects of aliskiren and the combination of aliskiren plus valsartan, but not valsartan alone, indicating that valsartan-induced cardioprotection was not mediated by the B 2 receptor. PD123319 reversed the cardioprotective effects of aliskiren, valsartan, and the combination of aliskiren plus valsartan. Aliskiren protects the heart from myocardial ischemia-reperfusion injury via a B 2 receptor-and AT 2 receptor-mediated mechanism, whereas cardioprotection by valsartan is mediated via the AT 2 receptor. In addition, aliskiren attenuates valsartan-induced increases in angiotensin II levels, thus preventing AT 2 receptor-mediated cardioprotection by valsartan. MethodsDetailed methods are provided in the online-only Data Supplement. Results Effects of Drug Treatment on Systolic BloodPressure, Body Weight, Heart Weight/Body Weight Ratio, and Mean Arterial Blood Pressure During I/R Injury Systolic blood pressure (SBP) of the 12 groups of rats during the 4-week treatment period before I/R injury is shown in the Table. In the present study, we used doses of aliskiren (10 mg/kg per day SC) and valsartan (30 mg/kg per day PO) that have little effect on blood pressure in normotensive Sprague-Dawley rats. Neither aliskiren nor valsartan caused any change in SBP during the 4 weeks (Table). However, SBP in rats receiving the combination of aliskiren plus valsartan was less than that in vehicle-treated rats. In contrast, SBP in rats receiving the B 2 receptor antagonist icatibant (0.5 mg/kg per day SC) alone was higher than that of vehicle-treated rats. Rats treated with aliskiren, valsartan, and the combination of aliskiren plus valsartan had lower SBP during combined treatment with icatibant than that of rats treated with icatibant alone. Treatment with the AT 2 receptor antagonist PD123319 (30 mg/kg per day SC) alone did not affect blood pressure. During combined treatment w...

show abstract

Section: Discussionmentioning

confidence: 66%

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

2014

View full text Add to dashboard Cite

show abstract

“…It was initially suggested that a combined treatment with aliskiren and an ACE inhibitor, or an angiotensin receptor blocker, could offer major benefits in patients with elevated cardiovascular risk. However, recently, concerns have raised about the clinical use of aliskiren in patients with NIDDM, especially when associated with ACE inhibitors, by the results of at least a couple of studies, 44,45 suggesting that the addition of aliskiren to standard therapy with renin-angiotensin system blockers might be even harmful. 44 Also in nondiabetic patients, there are concerns about the association of aliskiren with ACE inhibitors or angiotensin receptor blockers.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

et al. 2014

View full text Add to dashboard Cite

Abstract-Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus. An increased media-to-lumen ratio of subcutaneous smallresistance arteries is a potent predictor of cardiovascular events in patients with increased blood pressure values, [10][11][12] part of them being also diabetics.10,11 Antihypertensive treatment is able to regress structural alterations in subcutaneous small-resistance arteries of essential hypertensive patients 13 ; however, despite similar blood pressure-lowering effects, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptors blockers, and calcium channel blockers proved to be more effective than diuretics and β-blockers in terms of reduction in the media-to-lumen ratio. 13 The extent of the reduction in the media-to-lumen ratio of subcutaneous small-resistance arteries was recently demonstrated to be an independent predictor of cardiovascular events in essential hypertension. 14 However, in patients with diabetes mellitus, it seems more difficult to obtain a complete regression of small-resistance artery structural alterations, despite prolonged treatment. 15-18A possible explanation is related to the presence, in patients with diabetes mellitus, of hypertrophic remodeling of small arteries, which repre...

show abstract

“…Among patients hospitalized for worsening chronic heart failure with reduced left ventricular ejection fraction, adding aliskiren (150-300 mg/day) to standard therapy did not reduce cardiovascular death or heart failure rehospitalization at 6 months or 12 months after discharge. Moreover, the rates of hyperkalaemia, hypotension, and renal impairment/ renal failure were higher in the aliskiren group compared with placebo [43]. According to the European Society of Cardiology -Heart Failure Association, aliskiren is not presently recommended as an alternative to an ACE inhibitor or ARB in patients with heart failure [44].…”

Section: Pharmacology Of Aliskirenmentioning

confidence: 99%

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

Łukawski¹,

Baranowicz-Gąszczyk²

2017

J Pre Clin Clin Res.

View full text Add to dashboard Cite

Łukawski K, Baranowicz-Gąszczyk I. Aliskiren -an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease. J Pre-Clin Clin Res. 2017; 11(1): 81-85. doi: 10.26444/jpccr/75295 Abstract Introduction. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hypertension, cardiovascular diseases (CVDs) and chronic kidney disease (CKD). Drugs affecting the RAAS system, such as angiotensinconverting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and heart failure. These drugs are also effective in reducing proteinuria and may, at least, delay end-stage renal disease in both diabetic and non-diabetic proteinuric CKD. However, novel drugs are needed to more effectively suppress the RAAS system and the progression of CKD. Aliskiren is the first direct renin inhibitor which has been approved for the treatment of hypertension. Additionally, a number of clinical studies have shown the antiproteinuric effect of aliskiren.Objective. This review focuses on the antihypertensive and antiproteinuric effects of aliskiren in patients with CKD. The pharmacology of aliskiren in these patients is also provided. Conclusions. Aliskiren-based hard endpoint large trials in non-diabetic nephropathy are needed in order to clarify the use of aliskiren in CKD patients.

show abstract

Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure

Cited by 316 publications

References 30 publications

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

Contact Info

Product

Resources

About

Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure

Cited by 316 publications

References 30 publications

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B 2 Receptor– and Angiotensin AT 2 Receptor–Mediated Mechanism

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B 2 Receptor– and Angiotensin AT 2 Receptor–Mediated Mechanism

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

Contact Info

Product

Resources

About

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism