Related Experiment Video
Updated: May 17, 2026
Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
Cardiorenal end points in a trial of aliskiren for type 2 diabetes
Hans-Henrik Parving1, Barry M Brenner, John J V McMurray
1Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. hhparving@dadlnet.dk
Insights
Adding aliskiren to standard therapy for high-risk type 2 diabetes patients did not reduce cardiovascular and renal events and increased risks of hyperkalemia and hypotension. These findings suggest potential harm, not benefit, from this combination therapy.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Patients with type 2 diabetes and high cardiovascular/renal risk often require multifaceted treatment.
- The direct renin inhibitor aliskiren was investigated for its potential to reduce adverse events in this population.
Purpose of the Study:
- To evaluate the efficacy of aliskiren as an adjunct to renin-angiotensin system blockade in reducing cardiovascular and renal events.
- To assess the safety profile of combined aliskiren and standard therapy.
Main Methods:
- A double-blind, randomized trial involving 8561 patients with type 2 diabetes and high cardiovascular or renal risk.
- Patients received either aliskiren (300 mg daily) or placebo, alongside an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker.
- The primary endpoint was a composite of major adverse cardiovascular and renal events.
Main Results:
- The trial was terminated early due to lack of efficacy; no significant difference in the primary endpoint was observed between aliskiren and placebo groups (18.3% vs. 17.1%).
- Aliskiren led to lower blood pressure and greater reduction in albuminuria but significantly increased rates of hyperkalemia and hypotension.
- Secondary renal endpoints showed similar effects, with no significant benefit observed.
Conclusions:
- Adding aliskiren to standard renin-angiotensin system blockade in high-risk type 2 diabetes patients is not beneficial and may increase harm.
- The combination therapy showed an increased risk of adverse events, including hyperkalemia and hypotension, without improving cardiovascular or renal outcomes.
Background:
This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both.
Methods:
In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level.
Results:
The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons).
Conclusions:
The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:28Diabetic Nephropathy
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:28Chronic Kidney Disease III: Interprofessional Care
01:25Chronic Kidney Disease I: Introduction