Gary A. Ford

Background and Purpose— Risks and benefits of intravenous thrombolysis for patients with stroke >80 years of age are unclear. We examined outcomes and symptomatic intracerebral hemorrhage rates in ≤80- and >80-year-old patients in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register. Methods— We compared mortality and independence (modified Rankin Scale 0 to 2) at 3 months and symptomatic intracerebral hemorrhage (per Safe Implementation of Treatment in Stroke ≥4-point deterioration in National Institutes of Health Stroke Scale within 36 hours and Type 2 parenchymal hemorrhage and per National Institute of Neurological Disorders and Stroke [any increase in National Institutes of Health Stroke Scale and any hemorrhage]) of 1831 patients >80 years of age with 19 411 patients ≤80 years of age compliant with other European licensing criteria. Results— The >80-year-old group (median, 83 years) had more severe strokes (median National Institutes of Health Stroke Scale 14 versus 12), lower levels of prestroke independence (modified Rankin Scale 0 to 1, 82% versus 93%), and a larger proportion of females (59% versus 39%) compared with the younger group (68 years). Symptomatic intracerebral hemorrhage was not significantly increased after adjustment for other risk factors in those >80 years of age compared with those ≤80 years of age (per Safe Implementation of Treatment in Stroke 1.8% versus 1.7%, P =0.70, adjusted OR, 0.90, 95% CI, 0.73 to 1.09; P =0.28; per National Institute of Neurological Disorders and Stroke 9.5% versus 7.8%, P 80 years of age had a higher mortality rate (30% versus 12%; P P P P 80 years of age otherwise fulfilling the intravenous alteplase license criteria have a similar rate of symptomatic intracerebral hemorrhage compared with younger patients and are appropriate candidates for thrombolysis. The higher mortality and the poorer functional outcome are consistent with the overall worse prognosis seen in the natural history of this age group.

Blood pressure (BP) lowering in people who have had a stroke or transient ischaemic attack (TIA) leads to reduced risk of further stroke. However, it is not clear what the target BP should be, since intensification of therapy may lead to additional adverse effects. PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting, and whether more intensive therapy is associated with adverse effects on quality of life. This is a randomised controlled trial (RCT) in patients with a past history of stroke or TIA. Patients will be randomised to two groups and will either have their blood pressure (BP) lowered intensively to a target of 130 mmHg systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg) compared to a standard group where the BP will be reduced to a target of 140 mmHg systolic. Patients will be managed by their practice at 1-3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months. 610 patients will be recruited from approximately 50 general practices. The following exclusion criteria will be applied: systolic BP <125 mmHg at baseline, 3 or more anti-hypertensive agents, orthostatic hypotension, diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness. The primary outcome will be change in systolic BP over twelve months. Secondary outcomes include quality of life, adverse events and cardiovascular events. In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals understanding and views of BP management. The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care, and help determine whether or not further research is required before recommending such targets for this population. ISRCTN29062286

The demonstration of the ischaemic penumbra in animal models and the effectiveness of reperfusion therapy in humans led to considerable optimism for neuroprotection in acute stroke. Initial experience with failure of phase II and III trials led to the STAIR recommendations for pre-clinical and clinical studies. Review of pre-clinical studies suggests that selection of agents for clinical development may not have been optimal. The neuroprotective agent NXY-059 fulfilled pre-clinical and many clinical STAIR criteria but a second large phase III study failed to demonstrate any benefit. Many of the STAIR criteria have not been fulfilled in the development of recent neuroprotective agents. Other issues not addressed include the use of animal models more reflective of older stroke patients with physiological derangement, demonstration of drug distribution to the proposed site of action in humans, selection of patients with salvageable tissue, achieving very early treatment, refinement of measurement of neurological impairment and disability, and physiological optimization in proof of concept human studies. Increasing the number and quality of clinical centres undertaking acute stroke research, use of surrogate imaging markers and adaptive dose designs in phase II trials could improve the likelihood of identifying an effective neuroprotective. Neuroprotection in acute stroke remains a significant challenge but has not been clearly shown to be ineffective. Given the profound burden of stroke and limited applicability of reperfusion to currently at best 10% patients, further proof of concept studies of neuroprotection remain indicated with careful review of pre-clinical data and more rigorous phase II trial design.

The assessment of circadian blood pressure change by ambulatory blood pressure monitoring has potential as a predictor for cardiovascular events, but its evaluation is problematic due to the difficulty in defining day and night periods for individual subjects. The cumulative sums (cusums) method has the advantage of simplicity over mathematical modelling techniques and is reported to give more reproducible results than methods that use time-dependent sleep and wake periods. However, cusum parameters (cusum-derived circadian alteration magnitude (CDCAM) and cusum plot height (CPH)) are affected by the implementation of the method and by the quality of ambulatory blood pressure recordings. This study quantifies the effects of using interval blood pressure values, changing the time used for calculating the cusum plot slope (CPS) and using incomplete data recordings. Significant effects are reported in all cases. Using interval rather than recorded blood pressures causes a mean reduction in CPH and CDCAM of approximately 6%. Altering the CPS time by 1 h (from 6 h) results in a mean change in CDCAM of approximately 7%. In recordings with hourly readings, the coefficient of variation in CPH and CDCAM ranges from 4% (one missing reading) to 13% (five missing readings).

Gary A. Ford; Thrombolysis for stroke in the over 80s, Age and Ageing, Volume 33, Issue 2, 1 March 2004, Pages 95–97, https://doi.org/10.1093/ageing/afh060

Background and Purpose— Timely referral of appropriate patients to acute stroke units is necessary for effective provision of skilled care. We compared the characteristics of referrals with suspected stroke to an academic acute stroke unit via 3 primary referral routes: ambulance paramedics using a rapid ambulance protocol and stroke recognition instrument, the Face Arm Speech Test; primary care doctors (PCDs); and emergency room (ER) referrals. Methods— Patient characteristics, final diagnosis, and admission delay were recorded in all suspected acute stroke referrals in a 6-month period. Results— Four hundred eighty-seven patients (356 strokes/transient ischemic attacks) were admitted by the 3 routes: 178 by ambulance, 216 by PCDs, and 93 through the ER. The proportion of nonstrokes admitted by each route was similar (23%, 29%, and 29%, respectively). Ambulance paramedics’ stroke diagnosis was correct in 144 of 183 (79%) stroke patients who initially presented to them. Thirty-nine of 66 strokes/transient ischemic attacks referred via ER were taken there following initial ambulance assessment. Compared with PCDs, paramedics referred more total anterior circulation (39% versus 14%, P P P Conclusions— Misdiagnosis of stroke is common in the ER and by PCDs. Paramedics using the Face Arm Speech Test achieved high levels of detection and diagnostic accuracy of stroke.

Objectives: the benefits of treatment of hypertension in older people are well‐established but implementation of this knowledge may be sub‐optimal. We have determined recent primary care management of older people with hypertension. Methods: we examined health records (n=6986) of a 1 in 7 sample of patients aged 65–80 years from a random sample of practices (n=51) in the former Northern Region of the UK, stratified by health authority, for the previous 6 years. We recorded documented risk factors, diagnosis of hypertension, three most recent blood pressure readings, current drug therapy and previous blood pressure lowering therapy, and presence of coexistent pathology. Results: blood pressure was defined as hypertensive (⩾160/⩾90 mmHg; one or both values above these limits), normotensive or undetermined using a validated algorithm. In 30% of patients, blood pressure status was undetermined. Thirty‐five percent of subjects were found to be hypertensive. Of these, 70% were receiving antihypertensive treatment but only 30% of treated patients had controlled (PPConclusions: treatment of hypertension in older people in primary care has improved in terms of detection and treatment but in only one‐third of patients is high blood pressure controlled. There remain important opportunities for prevention of stroke and myocardial infarction in this age group through achieving improved blood pressure control.