Impact of Antihypertensive Treatment on Outcomes of Adjuvant Bevacizumab for Ovarian Cancer ( <scp>IATRO</scp> ), Results from a Nationwide Emulated Clinical Trial

Antiangiogenic therapy with bevacizumab improves outcomes in ovarian cancer but induces hypertension, leading to major adverse cardiovascular events (MACE). While calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEi) are recommended for managing bevacizumab-associated hypertension, their impacts on cancer progression and cardiovascular outcomes are unclear. This study compared the effects of CCBs and ACEi on progression-free survival (PFS) in ovarian cancer patients treated with adjuvant bevacizumab. The incidence of MACE and overall survival (OS) were also evaluated. We conducted an emulated clinical trial using data from January 1, 2011, to January 1, 2021, from the French National Health Data System (SNDS), covering 98.8% of the French population. Patients with FIGO stage III to IV ovarian cancer who underwent cytoreductive surgery and adjuvant chemotherapy with bevacizumab, treated with CCBs or ACEi monotherapy within 6 months after surgery, were included. Out of 4,165 patients treated with bevacizumab, 454 met inclusion criteria for the main analysis: 273 in the CCBs group and 181 in the ACEi group. CCBs use was associated with a longer median PFS compared to ACEi (21.8 vs. 18.2 months) and a higher 3-year PFS rate (difference of 8.2 percentage points, 95% CI: 2.0%; 14.8%). No significant difference in OS was observed between groups. Cardiovascular complications were more frequent with CCBs compared to ACEi, particularly congestive heart failure (difference in 3-year incidence of MACE: -4.5 percentage points; 95% CI: -8.2%; -1.1%). These findings emphasize the need for a balanced approach to managing hypertension in cancer patients, considering both oncologic and cardiologic outcomes.