Secondary prevention after ischaemic stroke: the ASPIRE-S study

Stroke is a leading cause of death and disability resulting in substantial personal and healthcare costs. Although age-standardised rates of stroke mortality have decreased, the absolute number of people suffering stroke annually, stroke survivors and overall stroke burden are increasing [1]. Approximately 30 % of strokes occur in individuals with a previous stroke and 50 % occur in those with previous vascular events of any kind [2]. High recurrence rates emphasize the importance of effective preventive strategies and many population-based studies have reported strong associations between numerous cardiovascular risk factors and future stroke risk [2–4]. These findings have informed the development of evidence-based guidelines on stroke prevention [5, 6] which aim to improve stroke outcomes.

The EUROASPIRE surveys [7–9] drew attention to the continuing gap between standards set in guidelines on secondary cardiovascular disease prevention (in patients with coronary heart disease) and results achieved in clinical practice. More recently, a stroke-specific module retrospectively added to EUROASPIRE III concluded that risk factor control after IS also requires improvement [10].

We report a prospective, multi-centre study which assessed the extent to which evidence-based care was provided to a sample of Irish patients admitted with IS, as part of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) study. This study reviewed three components of IS care following discharge, including the adequacy of secondary prevention, delivery of rehabilitative care and assessment of ongoing rehabilitative needs. This analysis focuses on the adequacy of secondary prevention at 6 months in the ASPIRE-S cohort.

This study reveals suboptimal control of many risk factors post IS despite the availability of evidence-based therapies and clear guidelines for secondary prevention. This cohort was at high-risk for recurrent stroke, with prevalent baseline risk factors, two-thirds over the age of 65 years, and one-quarter having previous stroke. These findings raise concern for health professionals and should prompt more intensive management of risk factors.

Studies have shown an association between TC, LDL and elevated TG with IS risk, especially among atherosclerotic and lacunar stroke subtypes [21]. Although mean lipid levels recorded at 6 months were not excessively high, many results were not at target. Only three-quarters of our cohort had TC at target (<4.5 mmol/L) with a similar proportion (77 %) having LDL at target (<2.5 mmol/L). However, these results compare favourably with those from EUROASPIRE III (49 and 55 % respectively at target) [8] and with results from the stroke-specific module of EUROASPIRE III [10], likely due to the higher uptake of lipid-lowering medications in our group. Outside the trial setting, there is currently no published data available on the adequacy of control of lipid levels specific to IS. Although the optimal LDL level for secondary stroke prevention is unclear, there is evidence from the SPARCL study that tight control (<1.8 mmol/L; achieved by only 44 % of our cohort) reduces recurrent IS risk by one quarter [22] and European guidelines now advise this target for high-risk patients [15].

Diabetes is independently related to a greater risk of IS (adjusted risk ratio, 2.26) [23]. For diabetic patients in ASPIRE-S with suboptimal control (HbA1c ≥ 7, 28 %), it is unknown (without access to patient notes at follow-up) whether the treating physician opted for less strict control in light of poorly tolerated hypoglycaemic episodes in some patients. Optimal target HbA1c levels in diabetic patients still remain the subject of much debate, and in most cases is individualised to particular patient characteristics [24]. Only 1.5 % of non-diabetic patients had FG ≥7 mmol/L. Four percent of patients had FG within the impaired fasting glucose range (≥6.1 mmol/L), but this rose to almost 10 % when the latest American Diabetes Association definition (≥5.6 mmol/L) was applied [16]. Diagnoses were not made on the basis of a single FG level in ASPIRE-S but it is known that early dietary and lifestyle modifications can delay or prevent the development of diabetes in patients with impaired FG [25].

The prevalence of obesity in the developed world has substantially increased over time [26]. Results from the Physician’s Health Study reported a significant increase in the relative risk of stroke with each unit increase of BMI, independent of the effects of other stroke risk factors [27]. Over two-thirds of our cohort had a BMI of ≥25 kg/m² with one quarter being classified as obese. These levels are higher than those reported in the general Irish population (overweight 39 % and obese 18 %) [28] and likely contribute to other stroke/cardiovascular risk factors such as hypertension, hyperlipidaemia and diabetes. Two-thirds of participants had abdominal obesity. These results suggest that a more active role for sustained professional support and motivation in achieving successful weight reduction post stroke is needed, including (repeated) clear advice on weight loss from health professionals, which positively impacts on weight loss behaviour [29]. Although multiple successful weight reduction interventions are available, the ability of patients post stroke to engage in vigorous exercise programmes may be limited. Studies to explore the effectiveness of interventions such as group education or dietary changes for weight loss specifically after stroke are limited. The first randomized-controlled trial to evaluate the efficacy and safety of a weight management intervention in stroke survivors using the SystemCHANGE™ approach is currently underway [30].

The INTERSTROKE study reported a doubling in the risk for IS in current smokers (OR 2.09, 1.75–2.51) [3]. Although smoking rates are reportedly decreasing over time [2], 16 % were still smoking in our cohort at 6 months. This reflects a smoking cessation rate of 41 % (compared with 81 % in the Irish subgroup of EUROASPIRE III and 40 % in the stroke-specific module) [8, 10]. Although physician advice to stop smoking is the most important first step in the cessation process, this advice must be reiterated and reinforced by all health professionals [31]. Multiple pharmacotherapies for tobacco dependence have been shown to increase smoking cessation rates [32], and behavioural interventions can further increase the success of smoking cessation [33].

Although the mean BP reading was not excessively elevated, only 37 % of patients had BP ≤140/90 (similar to EUROASPIRE stroke module; 38 %). Such poor control of BP may reflect a lack of focus on secondary preventive initiatives for patients after stroke. The proportion at target was lower amongst patients with a previous diagnosis of hypertension and amongst those on anti-hypertensive therapy, reflecting the difficulty in treating hypertension in clinical practice. Recent European guidelines [5, 15] suggest a lower BP target of ≤130/80 in patients after IS, where tolerated. Only 16 % of our cohort achieved this target at 6 months and this proportion dropped to 13 % amongst those on anti-hypertensive therapy. Although these results reflect a single reading in patients, they are a reminder that better management of BP is required after IS including greater up-titration of medication dosages and use of multiple medication regimens in addition to lifestyle advice.

Ambulatory BP monitoring (reflecting multiple measurements) is known to provide a more accurate measure of BP control [34]. This is one of the first studies to describe ambulatory BP control post acute stroke and results clearly demonstrate greater overall BP control, compared with office readings. Better control of daytime (versus nightime) readings may reflect the timing of administration of antihypertensive medications (usually in the morning) which impacts on circadian control [35]. It may also reflect lack of attention placed by physicians on nightime BP control. Nightime BP control has been strongly linked to an increased risk of cardiovascular disease in multiple studies, including the Dublin outcome study of 5292 participants [36], which reported a relative hazard ratio (for cardiovascular mortality) of 1.21 for each 10-mm Hg increase in nightime systolic BP. This increased risk remained significant in older patients [36, 37].

Most IS patients are prescribed a combination of cardiovascular medications and this multi-factorial approach to secondary stroke prevention can result in a substantial reduction (of up to 80 %) in future stroke risk [38]. Although prescription rates of anti-thrombotic and lipid-lowering medications in our cohort were high, the prescription of anti-hypertensive medications appeared suboptimal. Despite positive findings from the pivotal PROGRESS study [39], a minority of patients in ASPIRE-S were on dual ACE I and diuretic therapy. However, a significant proportion of patients had hypertension (58 %), atrial fibrillation (40 %) and/or heart disease (30 %) at baseline and were likely already established on appropriate medications with anti-hypertensive effects (such as beta-blockers or CCBs) prior to their stroke.

This study has many strengths including its prospective design, large sample size, high rate of follow-up, in-hospital assessment of patients to verify eligibility for inclusion and a standardised follow-up assessment at 6 months modelled on previous robust EUROASPIRE surveys. There is little information in the stroke literature on the adequacy of secondary prevention after IS and much of the findings from ASPIRE-S are therefore novel. The recent EUROASPIRE III stroke-specific module (including four countries) reported some comparable findings but was retrospective, excluded IS patients over 80, had a broader follow-up period (6–36 months), used self-reported definitions of vascular risk factors and unhealthy lifestyle habits, did not include ambulatory BP monitoring and had limited generalizability.

Given the strong evidence from consensus of expert opinion for multi-dimensional risk factor management in secondary stroke prevention [38] it is imperative that tailored programmes of care (including risk factor control) be optimised. These should commence during the patients’ hospital admission with seamless transfer to the community. Over recent years there have been significant advances in the standardisation of clinical guidelines for stroke care, however the introduction of national stroke clinical guidelines alone is insufficient to improve health care quality [42]. For efficacy, guidelines should be incorporated into quality assurance cycles with education programmes and local feedback [43]. Results from ASPIRE-S promote awareness of the importance of ongoing surveillance of cardiovascular risk in patients after IS and prompt further roll-out of similar surveys internationally. This should encourage the establishment of local policies which support comprehensive, professional, multi-disciplinary secondary preventive initiatives, accessible to all survivors of stroke.