December 22, 2011

Novartis announces termination of ALTITUDE study

Novartis announced the termination of the ALTITUDE study in high-risk patients with diabetes and renal impairment.

The study was designed to determine if aliskiren could reduce cardiovascular and renal morbidity and mortality, compared with placebo, when added to conventional treatment (including ACEi or ARB).

Based on the recommendation from the Data Monitoring committee, it was felt patients were unlikely to benefit from aliskiren added in addition to standard therapy.  More importantly, the aliskiren arm had more frequent adverse events, including non-fatal stroke, renal complications, hyperkalemia and hypotension.

The peer reviewed publication has not yet been published.  The full text link provides the Novartis press release.

Related Articles:

Chronic Kidney Disease, Hypertension, RAS Blockade
  • Carlos Arturo Tilac

    Con estos resultados, los nefrologos quedamos a la intemperie para el tratamiento de las nefropatias proteinuricas. Debemos volver al bloqueo dual? o añadir los calcioantagonistas al bloqueo del SRAAA?
    Dr. Carlos A. Tilac

  • guest nephrologist

    In my opinion It’s not the drug to blame, but study design. Look at the rationale NDT paper http://1.usa.gov/sEiwRm
    “ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged > or =35 years): those with either urinary albumin/creatinine ratio (UACR) > or =200 mg/g; microalbuminuria (UACR) > or =20 or =30 or =30 <60 mL/min/1.73 m2 with or without microalbuminuria."2 main points1. ALTIDUDE is NOT a hypertension study, but a 'high CV risk study" Like ONTARGET patients are included (reimbursement pressure?) that I never would treat with double RAAS-blockade, ie patients with only eGFR 30-60, or patients with only CV risk without hypertension or albuminuria, In these groups the risk of the reported side effects (hyperkalemia, hypotension, GFR decline) would be extremely high.2. Safety was NOT addressed by home blood pressure measurements. Differences in office and home pressure are probably very relevant in a lot of ' high risk' patients.Subgroup analysis will be important to address the question whether aliskiren is still safe in diabetic patients with hypertension (@home:disqus /night) and albuminuria aiming for HOME bp of 130/80. In these patients I personally do not stop the drug. 

  • Maybe cautiously adding an aldo blocker to a background of ACEi or ARB.
    Strangely enough, a very old drug seems to have a moderate antiproteinuric effect in DN:
    http://www.ncbi.nlm.nih.gov/pubmed/18433957
    http://www.ncbi.nlm.nih.gov/pubmed/20199178

  • LPT

    Hope they publish what they have, could be illuminating. I still use double blockade for mod-severe proteinuria. 

  • guest

    Dual blockade of the renin-angiotensin system seems out.  Based on ACCOMPLISH,  
    http://www.nephrologynow.com/publications/renal-outcomes-with-different-fixed-dose-combination-therapies-in-patients-with-hypertension-at-high-risk-for-cardiovascular-events-accomplish-a-prespecified-secondary-analysis-of-a-randomised-cont
    maybe we should be using more calcium channel blockers in combination with ACEi or ARB?

  • altart

    Now what do we use?