Randomization, Masking, and Crossover
Patients, researchers, and clinical staff conducting exercise tests were blinded to the patients’ invasive physiological characteristics (phenotype-blinding). Exercise-testing staff were also blinded to the study medication. All eligible study patients were randomly assigned to receive either amlodipine or ranolazine (in a 1:1 allocation ratio) using an automated randomization tool; no stratification or blocks were used. Patients who were already taking a calcium channel antagonist or ranolazine were requested to withhold them from 4 weeks before their baseline visit until the end of the study.The initial doses were either amlodipine 5 mg once a day or ranolazine 375 mg twice a day, with an increase to amlodipine 10 mg once a day and ranolazine 500 mg or 750 mg twice a day after 1 to 2 weeks. If patients did not tolerate amlodipine 5 mg, then the dose was reduced to 2.5 mg. Four weeks after randomization, patients returned for the second exercise treadmill test (ETT), after which a 1-week drug-washout period was applied (a duration >5 half-lives of either medication, to minimize potential carryover effectsAfter the fourth ETT (or third for those who did not undertake the fourth ETT), study participation was complete, and patients and physicians were unblinded to the patients’ phenotype. Figure 
Study flow.
