Objective To prospectively assess if opiate antagonist treatment or the opiate-free status could reverse opiate-related vasculopathy.

Design Longitudinal Open Observational, Serial ‘N of One’, over 6.5 years under various treatment conditions: opiate dependence, naltrexone and opiate-free.

Setting Primary care, Australia.

Participants 20 opiate-dependent patients (16 males: 16 cases of buprenorphine 4.11±1.17 mg, two of methadone 57.5±12.5 mg and two of heroin 0.75±0.25 g).

Intervention Studies of central arterial stiffness and vascular reference age (RA) were performed longitudinally by SphygmoCor Pulse Wave Analysis (AtCor, Sydney).

Primary outcomes Primary outcome was vascular age and arterial stiffness accrual under different treatment conditions.

Results The mean chronological age (CA) was 33.62±2.03 years. The opiate-free condition was associated with a lower apparent vascular age both in itself (males: p=0.0402 and females: p=0.0360) and in interaction with time (males: p=0.0001 and females: p=0.0004), and confirmed with other measures of arterial stiffness. The mean modelled RA was 38.82, 37.73 and 35.05 years in the opiate, naltrexone and opiate-free conditions, respectively. The opiate-free condition was superior to opiate agonism after full multivariate adjustment (p=0.0131), with modelled RA/CA of 1.0173, 0.9563 and 0.8985 (reductions of 6.1% and 11.9%, respectively).

Conclusions Data demonstrate that opiate-free status improves vascular age and arterial stiffness in previous chronic opiate users. The role of opiate antagonist treatment in achieving these outcomes requires future clarification and offers hope of novel therapeutic remediation.