UC Davis

OBJECTIVES: To evaluate cardiovascular safety outcomes in estetrol 15 mg/drospirenone 3 mg users with cardiovascular risk factors. STUDY DESIGN: We performed a secondary analysis of two open-label contraceptive phase-3 trials that enrolled participants 16 to 50 years to use estetrol/drospirenone for up to 13 cycles. Study exclusion criteria included >35 years and smoking, body mass index >35 kg/m², and baseline blood pressure (BP) >140/90 mmHg. We compared adverse event rates in participants with and without cardiovascular risk factors and assessed discontinuation rates for cardiovascular adverse events. RESULTS: Of 3417 participants, 1410 (41.3%) had one or more, and 309 (9.0%) had two or more cardiovascular risk factors. We found no difference in discontinuation for any adverse events in participants with and without cardiovascular risk factors. Six (0.18%) participants discontinued for a cardiovascular complaint including four with risk factors: three (0.09%) due to hypertension (all had baseline BP ≥130/85 mmHg and one or more additional risk factors) and one due to venous thrombosis (BP ≥130/85 mmHg). Of 375 participants with baseline BP ≥130/85 mmHg, 0.8% (95% CI 0%-1.7%) discontinued for hypertension while among the 192 participants with baseline BP ≥130/85 mmHg and one or more additional cardiovascular risk factors, 1.6% (95% CI 0%-3.3%) discontinued for hypertension. CONCLUSIONS: Among >1400 study participants with cardiovascular risk factors using estetrol/drospirenone, only three (0.2%) discontinued for hypertension, all of whom had high-normal baseline BP and at least one other risk cardiovascular risk factor. IMPLICATIONS: Estetrol/drospirenone use demonstrates excellent cardiovascular tolerance in study participants with normal and high-normal blood pressure, even in those with cardiovascular risk factors. The very low rate of hypertension, even when cardiovascular risk factors were present, provides evidence to warrant clinical trials of estetrol/drospirenone in patients with hypertension desiring contraception.