[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Debate Not Which, But “If”
    Bharat Sachdeva, Associate Professor | LSU Heath SHREVEPORT
    I read with interest this study comparing the benefit of one drug vs another to bind phosphate and lower mortality.

    There is yet not one RCT that has shown that lowering phosphate, no matter how, reduces CKD or ESRD mortality.

    Diet exposure is the key. If one hot dog has 100 mg of phosphate you will need 4 calcium acetate or 5 sevelamer pills at a cost of ($15-$25) to bind all the phosphate in that hot dog. 

    Phosphate binders have given physicians a fall sense of security and an excuse to patients to increase phosphate
    intake knowing they can manage their levels with a binder. But the fact remains that binders will bind few mg of the total 1000+ mg that we ingest every day.

    It’s time we rethought our focus of managing phosphate in CKD patients toward a primary reduction of intake, as there is no evidence so far that phosphate binders will help them on meaningful measures of clinical outcomes.
    Original Investigation
    May 6, 2019

    Cardiovascular Outcomes of Calcium-Free vs Calcium-Based Phosphate Binders in Patients 65 Years or Older With End-stage Renal Disease Requiring Hemodialysis

    Author Affiliations
    • 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
    • 2Renal Section, Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
    • 3New England Geriatrics Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
    • 4Harvard Medical School, Boston, Massachusetts
    JAMA Intern Med. 2019;179(6):741-749. doi:10.1001/jamainternmed.2019.0045
    Key Points

    Question  Is the calcium-free phosphate binder sevelamer carbonate associated with superior cardiovascular end points compared with calcium acetate in patients 65 years or older with end-stage renal disease who are undergoing dialysis?

    Findings  In this cohort study of data from 2639 patients 65 years or older with end-stage renal disease in the United States Renal Data System, a similar risk of cardiovascular events and death between sevelamer and calcium acetate initiators was noted after adjusting for 78 potential confounders, including serum calcium and phosphorous levels.

    Meaning  This null result suggests that any potential increased safety of sevelamer compared with calcium-based phosphate binders on cardiovascular events observed in previous small trials with nonrepresentative populations may not translate into routine clinical practice; this observation questions the high cost incurred to national budgets by use of sevelamer and calls for well-designed randomized clinical trials.


    Importance  Guidelines restricting use of calcium-based phosphate binders in all patients with end-stage renal disease owing to their potential contribution to increased cardiovascular risk shifted prescribing from calcium acetate toward the costlier sevelamer carbonate products.

    Objective  To compare cardiovascular events and mortality between patients with end-stage renal disease (ESRD) undergoing hemodialysis receiving sevelamer vs calcium acetate in real-world practice.

    Design, Setting, and Participants  An observational cohort study was conducted using the United States Renal Data System linked to Medicare claims data (May 1, 2012, to December 31, 2013). Data analysis was performed from October 2017 to September 2018. Participants included patients 65 years or older with ESRD within 180 days after starting hemodialysis (sevelamer, 2647; calcium acetate, 2074).

    Exposures  New use of sevelamer (calcium-free phosphate binder) vs calcium acetate (calcium-based phosphate binder).

    Main Outcomes and Measures  Hazard ratios (HRs) with 95% CIs were estimated for fatal or nonfatal cardiovascular events (myocardial infarction or ischemic stroke: primary outcome) and all-cause mortality (secondary outcome) using Cox proportional hazards regression with fine stratification on the propensity score to control for potential confounders, including phosphorus and calcium levels.

    Results  After propensity score weighting, 2639 patients initiating sevelamer treatment (1184 men [44.9%]; mean [SD] age, 75.6 [6.9] years) and 2065 patients initiating calcium acetate treatment (930 men [45.0%]; mean [SD] age, 75.5 [7.1] years) were included in the analysis. Crude incidence rates (IRs) for cardiovascular events of 458 per 1000 person-years for sevelamer and 464 per 1000 person-years for calcium acetate were observed. After propensity score fine-stratification weighting, HRs of 0.96 (95% CI, 0.84-1.10) for cardiovascular events were observed. Results were consistent within subgroups of age (<75 y: primary outcome, HR, 1.02; 95% CI, 0.85-1.24; vs ≥75 years: primary outcome, HR, 0.83; 95% CI, 0.69-1.01) and sex (primary outcome in men: HR, 1.02; 95% CI, 0.83-1.26).

    Conclusions and Relevance  The results of the study do not suggest increased cardiovascular safety of sevelamer in the routine clinical practice of patients with ESRD compared with calcium acetate; this study’s findings suggest that well-designed, long-term, randomized clinical trials are needed.