The debates surrounding the TOPCAT trial raise some difficult questions.
- Should clinical research be further globalised?
- Should the findings of clinical trials be distrusted if the patients were mostly recruited from countries with a less strict research tradition and discipline?
- Should checks on compliance involve more than just asking questions and counting pills, and involve serum level measurements, as was done in a subgroup of the trial sample?
- Is the cautious conclusion justified that spironolacton is effective for HfpEF after all, provided the diagnosis is accurate and an ‘as-treated’ (per-protocol) analysis is used instead of intention-to-treat analysis?
The answer to these questions can only be provided by a well-designed new trial investigating the same research question.
- de Denus S, et al. Spironolactone metabolites in TOPCAT—New insights into regional variation. N Engl J Med 2017; 376: 1690-1692.
- Pitt B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370: 1383-1392.
- Y.M. Smulders, et al. Diastolisch hartfalen: stand van zaken. NTVG 16-12-2003 https://www.ntvg.nl/artikelen/diastolisch-hartfalen.
- Redfield MM. Heart failure with preserved ejection fraction. N Engl J Med 2016; 375: 1868-1877.
- McMurray JVV, et al. Lessons from the TOPCAT trial. N Engl J Med 2014; 370: 1453-1454.
- Pfeffer MA, et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosteron antagonist (TOPCAT) trial. Circulation 2015; 131: 34-42.
- Pocock SJ, et al. Clinical trials series: The primary outcome fails: what next? N Engl J Med 2016; 375: 861-870.
*The literature refers to the Dutch text