ALTITUDE
Trial question
What is the role of aliskiren in patients with T2DM and CKD and/or CVD?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
32.0% female
68.0% male
N = 8561
8561 patients (2735 female, 5826 male)
Inclusion criteria: patients with T2DM and CKD and/or CVD
Key exclusion criteria: type 1 DM, unstable serum creatinine, congestive HF NYHA class III or IV, renal artery stenosis, malignancy within the past 5 years, renal artery stenosis, under immunosuppressive therapy, or pregnancy
Interventions
N=4274 aliskiren (at a dose of 300 mg daily plus angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker)
N=4287 placebo (matching placebo plus angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker)
Primary outcome
Cardiovascular death, cardiac arrest, nonfatal myocardial infarction, nonfatal stroke, unplanned hospitalization for heart failure, end-stage renal disease, renal death, renal replacement therapy, or doubling of baseline serum creatinine
18.3
17.1
18.3 %
13.7 %
9.2 %
4.6 %
0.0 %
Aliskiren
Placebo
No significant difference ↔
No significant difference in cardiovascular death, cardiac arrest, nonfatal myocardial infarction, nonfatal stroke, unplanned hospitalization for HF, ESRD, renal death, RRT, or doubling of the baseline serum creatinine (18.3% vs. 17.1%; HR 1.08, 95% CI 0.98 to 1.2)
Secondary outcomes
No significant difference in cardiovascular events (13.8% vs. 12.6%; HR 1.11, 95% CI 0.99 to 1.25)
No significant difference in renal events (6% vs. 5.9%; HR 1.03, 95% CI 0.87 to 1.23)
Safety outcomes
Significant differences in discontinuation of study drug (33.8% vs. 28.4%, p = 0.001) and discontinuation due to an adverse event (13.2% vs. 10.2%, p < 0.001); hyperkalemia (11.2% vs. 7.2%, p < 0.001), and hypotension (12.1% vs. 8.3%, p < 0.001).
Conclusion
In patients with T2DM and CKD and/or CVD, aliskiren was not superior to placebo with respect to cardiovascular death, cardiac arrest, nonfatal myocardial infarction, nonfatal stroke, unplanned hospitalization for HF, ESRD, renal death, RRT, or doubling of the baseline serum creatinine.
Reference
Parving HH, Brenner BM, McMurray JJ et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec 6;367(23):2204-13.
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