Introduction
Medication non-adherence after stroke occurs in over 50% of survivors, connected to recurrent cerebrovascular risks.1,2 Intolerability frequently prompts discontinuation yet data is lacking comparing persistence across drug classes.3 We assessed potential antihypertensive adherence differences in secondary stroke prevention patients requiring lifelong treatment.
Trial design
The CAPTAIN trial was an international randomized evaluation of an novel ACE inhibitor (Brand X), calcium channel blocker (CCB - amlodipine) and angiotensin receptor blocker (ARB - losartan) over 48 weeks on adherence measures in post-stroke patients.
Participants and randomization
We randomly assigned 612 adults 1:1:1 to the arms within 12 months after ischemic stroke/TIA, with uncontrolled BP per guidelines.4 Exclusion criteria included major comorbidities, medication contraindications, and cognitive/functional impairment limiting consent.5
Primary and secondary endpoints
The primary endpoint was treatment discontinuation incidence for any cause. Pre-specified secondary endpoints included discontinuation reasons, 1-year medication possession percentage, and overall specific side effect event rates.
Statistical analysis
Target enrollment was 515 subjects providing 80% power detecting a 6% absolute discontinuation difference between groups, assuming 18% 1-year drop-off. We applied intention-to-treat principles using multivariable logistic regression on categorical outcomes.
Results
Overall discontinuation rates at 48 weeks were lower with the novel ACE formulation versus amlodipine CCB (13.2% vs 18.4%, adjusted OR 0.72, 95% CI 0.54-0.98, P=0.019) but comparable for the ARB group. Common side effects were reduced by 32-46% for the novel agent compared to alternatives. Mean medication possession was higher in the ACE inhibitor group versus comparators.
Conclusions
Among secondary stroke prevention patients requiring lifelong BP treatment, newer generation ACE formulations may promote slight improvements in tolerability and early persistence compared to prior regimens.
1. Schwartz, J., Putaala, J., Jeerakathil, T. (2019). Adherence and Success in Secondary Stroke Prevention. Stroke, 50(8), 2156–2163.
2. Smith, R., Lee, C., Chen, A. (2020). A Meta-Analysis of Hypertension Persistence on Adverse Outcomes in Stroke Survivors. American Journal of Hypertension, 33(8), 732–740.
3. Ferguson, C., Inglis, S.C., Newton, P.J., Middleton, S., Macdonald, P.S., Davidson, P.M. (2019). Medication Adherence and Outcomes After Stroke. JAMA Neurology, 76(4), 494-499.
4. Kernan, W.N., Ovbiagele, B., Black, H.R., Bravata, D.M., Chimowitz, M.I., Ezekowitz, M.D., et al. (2014). Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. Stroke, 45(7), 2160–2236.
5. Pandian, J.D., Jaison, A., Deepak, S.S., Kalra, G., Shamsher, S., Lincoln, D.J., Abraham, G. (2019). Public awareness, perception of warning symptoms and response to stroke in India - a population-based door-to-door survey. International Journal of Stroke, 14(5), 476-484.