The primary outcome measure was time to first event for the composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospitalisation for heart failure, onset of end-stage renal disease or doubling of baseline creatinine.
The study enrolled patients with type 2 diabetes and renal impairment (n= 8,606) at high risk of cardiovascular and renal events. Details of the study design are shown here. I have also discussed the study in prior posts.
Reports about why the study was terminated have now emerged. Here is the presss release from
the executive steering committee:
"Median follow-up results from the ALTITUDE study,
stopped prematurely in December 2011
Munich, Germany – 26 August 2012: Preliminary results from
the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)
do not support administration of aliskiren on top of standard therapy with
renin-angiotensin-aldosterone system (RAAS) blockade in type 2 diabetics at
high risk of cardiovascular and renal events, according to Professor
Hans-Henrik Parving from Rigshospitalet, University of Copenhagen, Denmark.
Presenting results from the study today, he said the treatment “may even be
harmful”.
The ALTITUDE trial was stopped prematurely in December 2011
on recommendation of the data monitoring committee after it found an increased
occurrence of side effects and continuation of the study was deemed
“futile”. The study had been investigator initiated to determine whether use of
the direct renin inhibitor aliskiren would improve prognosis by reducing fatal
and non-fatal cardiovascular and renal events in type 2 diabetics at high risk
of these complications. Macro- and microvascular complications of type 2
diabetes are augmented in those with concomitant kidney and/or cardiovascular
disease.
ALTITUDE was an international double-blind study in 8561
subjects randomised to aliskiren 300 mg once daily or placebo on top of single
RAAS blockade. The primary outcome measure was time to first event for the
composite endpoint of cardiovascular death, resuscitated death, myocardial
infarction, stroke, unplanned hospitalisation for heart failure, onset of
end-stage renal disease or doubling of baseline creatinine.
- At a median follow-up of 32 months the primary composite endpoint had occurred in 767 patients (17.9%) assigned to aliskiren and 721 (16.8%) assigned to placebo, HR for aliskiren vs. placebo 1.08 (95% CI 0.98-1.20, p=0.14). Stroke occurred in 146 (3.4%) of the aliskiren and 118 (2.7%) in placebo, HR 1.25 (95% CI 0.98-1.60, p=0.070).
- Doubling of serum creatinine or end-stage renal disease was similar in the two groups and the mean reduction in albuminuria was 14% (95% CI 11-17) lower in aliskiren treated patients.
- Patients in the aliskiren group experienced significantly increased serum potassium ≥6 mmol/L (8.8% vs. 5.6%), and reported hypotension (12.1% vs. 8.0%).
