High screen failure rate in patients with resistant hypertension: Findings from SYMPLICITY HTN-3

The SYMPLICITY HTN-3 trial, which randomized subjects to renal denervation (RDN) or sham control, was designed to evaluate the efficacy and safety of RDN for the treatment of resistant hypertension. Outcomes were previously reported. This retrospective analysis evaluated reasons for screen failure (SF) for randomization in the trial.

SYMPLICITY HTN-3 enrolled subjects with office systolic blood pressure (SBP) ≥160 mmHg on stable and maximal doses of ≥3 antihypertensive medication classes. Blood pressure was measured during screening visit (SV) 1 and SV2 a minimum of 2 weeks later to ensure resistant hypertension and to exclude white-coat hypertension. We analyzed baseline characteristics and reasons for SF at each SV and changes in BP between SVs.

Among 1,415 patients screened, 880 (62%) did not meet criteria for randomization. Compared with randomized patients, those in the SF cohort were more likely to be older (58.7 vs. 57.4 years, P=.029), current smokers (14.5% vs. 10.7%, P=.041), and prescribed fewer antihypertensive medications (4.7 vs. 5.1, P<.001). The predominant reason for SF at SV2 was office SBP <160 mmHg despite office SBP ≥160 mmHg at SV1.

Screening patients with resistant hypertension on maximal doses of ≥3 antihypertensive drugs led to a high SF rate. Screen failures were most common at SV1 and were due to failing the office SBP entry criteria. Not meeting ambulatory SBP criteria at SV2 was a secondary reason for SF, often due to white-coat hypertension; thus, 24-hour ambulatory monitoring is important to validate resistant hypertension.