In 1999 a great multi-site clinical trial known as the randomized Aldactone evaluation study (RALES) showed that the use of spironolactone importantly reduced complications attributable to chronic heart failure without major negative side effects. Recently, RALES has been questioned by a large scale observational study in the Ontario population. In contrast with predictions, the complications and mortality increased dramatically because of hyperkalemia, reaching dimensions from a public health perspective are comparable to an epidemic. This review analyses both pieces of research in the light of Karl Popper’s science theory applying the modus tollens syllogism to the reality proposed by the main empirical enunciations that ensue from its epidemiological designs. RALES is deductively refuted because of the non-fulfillment of auxiliary assumptions that would act as reciprocal potential falsifiers in both studies, taking the logical form of a bi-conditional argument of the type: (a) P-then-Q and (b) Q-if-XP, XP being a set of potential falsifiers of Q as part of the explicit falsity content of P. From this popperian model, implications for clinical research are discussed.