We have reported that
anthracyclines and nonanthracycline chemotherapeutics caused diastolic dysfunction in
cancer patients without cardiovascular risk factors. Diastolic dysfunction occurred as early as 1 week after the last
chemotherapy cycle and manifested as impaired myocardial relaxation at echocardiography or persistent elevations of
B-type natriuretic peptide (BNP) or
troponin. The antianginal drug
ranolazine shows cardiac relaxant effects that we considered of value to treat early diastolic dysfunction induced by
cancer drugs; therefore, 24 low-risk patients with post-
chemotherapy diastolic dysfunction were randomized (1:1) to
ranolazine or the investigator's choice of common
cardiovascular drugs, such as β-blockers and/or
angiotensin-converting enzyme inhibitors or
loop diuretics (best standard
therapy, BST). After 5 weeks, 12 of 12 patients on
ranolazine recovered from diastolic dysfunction, whereas 3 of 12 patients on BST did not improve; however, adverse events (not serious) were apparently more frequent for
ranolazine than for BST (4/12 vs. 1/12).
Ranolazine did not lower blood pressure, whereas BST reduced systolic pressure and caused a trend toward a reduced diastolic pressure. Most patients at randomization showed
tachycardia resulting from
chemotherapy-related
anemia.
Hemoglobin recovery contributed to normalizing heart rate in these patients; however, some patients in the
ranolazine arm developed
tachycardia through chronotropic effects of high BNP levels and returned to a normal heart rate through the effects of
ranolazine on decreasing BNP levels. This minitrial describes the potential effects of
ranolazine on relieving
chemotherapy-related diastolic dysfunction; however, clinical implications of these findings need to be characterized by studies with an adequate sample size. SIGNIFICANCE STATEMENT: The antianginal drug
ranolazine causes cardiac relaxant effects that might relieve diastolic dysfunction. In a clinical pharmacology study, 24 patients were randomized (1:1) to receive
ranolazine or common
cardiovascular drugs to treat early diastolic dysfunction induced by
anthracycline-based or nonanthracycline
chemotherapy.
Ranolazine relieved diastolic dysfunction in these patients. The safety profile of
ranolazine in
cancer patients is similar to that of the general population. Compared with common
cardiovascular drugs,
ranolazine relieved diastolic dysfunction without lowering blood pressure. The sample size of this study was nonetheless too small to permit considerations about the potential clinical value of
ranolazine for oncologic patients with early diastolic dysfunction induced by
anthracyclines or nonanthracycline chemotherapeutics. This information should be obtained by studies with an adequate sample size.