Long term survival after a first transient ischaemic attack in England: A retrospective matched cohort study

Abstract

Objective: Transient ischaemic attacks (TIA) serve as warning signs for future stroke, and the impact of TIA on long term survival is uncertain. We assessed the long-term hazards of all-cause mortality following a first episode of a transient ischaemic attack (TIA).

Design: Retrospective matched cohort study.

Methods: Cohort study using electronic primary health care records from The Health Improvement Network (THIN) database in the United Kingdom. Cases born in or before 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Double-Cox Weibull survival model with a random frailty effect of general practice, while adjusting for different socio-demographic factors, medical therapies, and comorbidities.

Results: 20,633 cases and 58,634 controls were included. During the study period, 24,176 participants died comprising of 7,745 (37.5%) cases and 16,431(28.0%) controls. In terms of hazards of mortality, cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to their 39-60 years matched controls (HR = 3.04 (2.91 - 3.18)). The HR for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to their same-aged matched controls. Cases aged 39-60 at TIA onset who were prescribed aspirin were associated with reduced HR of 0.93 (0.84 - 1.01), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5, 10 and 15 years respectively, compared to the same aged cases who were not prescribed any antiplatelet. Statistically significant reductions in hazard ratios were observed with aspirin at 10 and 15 years in all age groups. Hazard ratio point estimates for other antiplatelets (dipyridamole or clopidogrel) and dual antiplatelet therapy were very similar to aspirin at 5, 10 and 15 years but with wider confidence intervals that included 1. There was no survival benefit associated with antiplatelet prescription in controls.

Conclusions: The overall risk of death was considerably elevated in all age groups after a first-ever TIA event. Aspirin prescription was associated with a reduced risk. These findings support the use of aspirin in secondary prevention for people with a TIA. The results do not support the use of antiplatelet medication in people without TIA.

Keywords: Antiplatelets; General practice; Multiple Imputation; The Health Improvement Network (THIN) database; Weibull-Cox model.