Importance of In-Hospital Initiation of Therapies and Therapeutic Inertia in Secondary Stroke Prevention
IMplementation of Prevention After a Cerebrovascular evenT (IMPACT) Study
Background and Purpose— Many patients do not receive prevention consistent with recommendations after stroke, but the relative importance of patient- and physician-related factors is uncertain.
Methods— We prospectively assessed factors associated with blood pressure (BP) <140/90 mm Hg and low-density lipoprotein (LDL) cholesterol <1 g/L in a collaborative cohort of 240 consecutive patients experiencing stroke/transient ischemic attack (Rankin <4; ≤80 years; no major comorbidity) from a stroke unit and 3 emergency departments. A standardized assessment of risk factors was performed 6 and 12 months after the initial event by an investigator who was not involved in the usual follow-up of patients.
Results— At 6 months, 41% of patients with diagnosed hypertension at inclusion had their BP <140/90 mm Hg and 55% of those with diagnosed hypercholesterolemia had their LDL <1 g/L. Adherence to treatment was excellent in 81% of patients. In univariate and multivariate analyses, initiation or reinforcement of appropriate treatments during hospitalization were the main factors associated with BP <140/90 mm Hg (OR=2.44; 95% CI: 1.20 to 4.97) and LDL <1 g/L (OR=3.36; 1.27 to 8.89) or with decrease in BP and LDL. Patients’ sociodemographic characteristics, education, income, knowledge of disease, and risk factors were not associated with control of BP or LDL. Among patients with BP ≥140/90 mm Hg, approximately 40% received either no treatment or one drug only, and treatment was reinforced in 20% of them only. Results were similar at 12 months with no improvement in the rate of control of risk factors.
Conclusion— Therapeutic inertia is an important impediment to achieve BP and LDL control goals after stroke, even in fairly motivated/adherent patients. In-hospital initiation of preventive therapies could improve quality of secondary stroke prevention in the long term.
Patients who have had a stroke or a transient ischemic attack (TIA) are at high risk for recurrent cerebrovascular and cardiac events.1,2 Both clinical trials and epidemiological studies provide unambiguous evidence supporting the efficacy of a variety of therapies to prevent recurrent events in those patients.1 Despite this evidence, there is a substantial gap between recommendations in guidelines and actual care of those patients.3 It has been estimated that up to 50% of patients with hypertension do not receive any treatment and among those who receive treatment, 30% to 60% have their blood pressure (BP) above recommended levels,4–7 50% have too high cholesterol levels,6,8 15% do not receive antiplatelet agents,9–12 and 50% of patients who are eligible for anticoagulation do not receive anticoagulants.10,12 Thus, improving adherence to guidelines is potentially a very powerful way to increase efficiency of stroke prevention. However, as shown in randomized clinical trials and meta-analyses, the different approaches developed to improve adherence to guidelines (eg, clinical practice guidelines, formal continuing medical education, and so on) during the last decade result in only modest improvements in care.13,14 In fact, most of these approaches are based more on beliefs than on scientific evidence.15 The identification of factors that influence the implementation of guidelines could allow developing new strategies to improve adherence to those guidelines. However, only a few studies have addressed those reasons and to date, potential determinants of adherence to guidelines have been identified mainly from qualitative research and the role of those determinants has rarely been quantified.9–11 We therefore assessed the proportion of patients who had their vascular risk factors controlled 6 and 12 months after stroke/TIA, the changes in these proportions over time, and addressed several potential determinants for adherence to guidelines for secondary stroke prevention.
IMplementation of Prevention After a Cerebrovascular evenT (IMPACT) was a prospective, observational collaborative cohort study carried out in 4 sites, including a stroke unit and 3 emergency departments, which were all used to collaborating with each other through a hospital network (participants are listed in Appendix 1). The study was approved by our institutional ethics committee and all patients signed an informed consent.
Eligible patients were consecutively identified from May 1, 2004, through June 30, 2005, by means of a prospective registry of all patients admitted for definite or suspected ischemic or hemorrhagic (excluding subarachnoid hemorrhage) stroke or TIA. Such a registry had been taking place in the stroke unit for several years and was set up at the beginning of the study in the other participating departments. Patients were eligible if they (1) were aged between 18 and 80; (2) had had an acute (<1 month) TIA or a nondisabling stroke (Rankin scale ≤3); (3) did not have major comorbidities (ie, advanced dementia, severe psychiatric disorder, cancer, and any cardiac, respiratory, or renal disorder limiting life expectancy in the short term); (4) could be followed during the study period; and (5) did not have a particular cause of stroke such as arterial dissection, cardiac tumor, or arteriovenous malformation, ie, diseases that do not justify traditional preventive measures. Thus, the population consisted of people for whom secondary stroke prevention was indisputably justified according to guidelines.1,16–19 All patients were enrolled in the study by the main investigator (M.V.) as soon as possible after their qualifying event. Physicians working at our stroke unit, general practitioners, and other physicians in charge of the patients were not informed of the patients’ participating in the study, but patients were free to inform them. At enrollment, sociodemographic characteristics, medical history, family history, clinical examination data, treatments having undergone before stroke, and treatments prescribed at discharge were collected from the patient and medical reports.
Follow-up assessments were performed by the main investigator or a trained research assistant 6 and 12 months after the qualifying event. At each follow-up assessment, 3 rest BP measurements were obtained over 5 to 10 minutes with the patient properly prepared and positioned using an automated device for upper arm (Omron M5-1).20 The mean of the last 2 measurements was used for the analyses. Lipid blood test was required in patients with ischemic event and hemoglobin A1c in patients with diabetes. Patients were asked about their ongoing treatments, current weight, and alcohol and tobacco consumption. Carbon monoxide was monitored in patients who declared having given up smoking since their stroke/TIA (Smoke Check Micro Medical). We also assessed the patients’ characteristics at each follow-up visit as follows: cognitive status (Mini-Mental Status test),21 knowledge of vascular risk factors (“Could you cite as many vascular risk factors as you know?”), knowledge that they had had a stroke (“Do you know the name of the disease you were admitted for to hospital?”),22,23 current depression and anxiety (MINI-500 instrument),24 and adherence to treatments (5-point Shea questionnaire, Appendix 2).25 For the latter, we considered patients who scored ≤1 as compliant.
We used the recommendations in force at the time.19,26–28 Primary outcomes were BP <140/90 mm Hg, low-density lipoprotein (LDL) cholesterol <1 g/L, and total cholesterol <2 g/L. Secondary outcomes included no smoking, alcohol consumption <40 g/d in men or <30 g/d in women, body mass index <25 kg/m2, and hemoglobin A1c ≤7% in patients with diabetes.
We hypothesized that the proportion of patients with uncontrolled BP and that of patients with uncontrolled LDL cholesterol would be 30% or more and that the prevalence of factors that could influence the rate of control of BP and LDL would be 20% or more. Based on these assumptions, we estimated that 400 patients were necessary to have a statistical power of 80% to detect ORs ≥2.0 with a 2-sided significance level of P<0.05. Patients with previously known hypertension, those for whom antihypertensive treatment was initiated during their hospitalization because of elevated BP, and those who had BP ≥140/90 mm Hg at inclusion were considered hypertensive and identified as the target population for BP control. Similarly, patients receiving lipid-lowering therapy for any reason and those who had total LDL cholesterol ≥1 g/L or total cholesterol ≥2 g/L during hospitalization were considered as having elevated cholesterol and were identified as the target population for cholesterol control. Categorical variables were compared with Pearson’s χ2 test, Fisher 2-tailed test, or McNemar χ2 test where appropriate. Continuous variables were compared with 2-tailed t tests, analysis of variance, or appropriate nonparametric tests. Relations between the control of risk factors and potential determinants were assessed by calculations of crude and adjusted ORs. Variables that were associated with risk factor control at a level of P<0.20 were entered in a logistic regression model and backwardly selected with P<0.10 (0.20 for tobacco and alcohol consumption) used as the cutoff for retention in the model. Finally, to take into account the regression toward the mean phenomenon, we assessed factors that were associated with a decrease in BP and cholesterol between inclusion and follow-up visits through multivariate linear regressions adjusted for baseline BP. We looked for one-to-one interactions. Analyses were performed with data from the 6-month and 12-month follow-up visits.
During the study period, 383 patients were eligible for inclusion (198 identified in one of the participating emergency departments and 185 in the stroke unit). Of these, 143 (37%) declined to participate (Figure 1). In comparison to patients who enrolled in the study, those who declined to participate had been admitted to emergency departments more often (62% versus 45%; P=0.001) were older (63.2±13.6 years versus 54.4±13.7; P=0.004), and were less likely to be current/past smokers (46% versus 65%; P<0.0001), but did not differ regarding the other main characteristics.
Table 1 lists the characteristics of the 240 patients included in the study; 109 patients were initially admitted to one of the participating emergency departments and 131 directly to the stroke unit. Sixty-eight (62%) of the 109 patients initially admitted to the emergency departments were thereafter admitted to the stroke unit and 41 to departments of internal medicine, cardiology, or neurology of various hospitals in our geographic area. The mean duration of hospitalization of patients not admitted to the stroke unit did not differ from that of those admitted to the stroke unit (10.4 versus 9.1 days; P=0.38). Median (interquartile range) time between the qualifying event and inclusion was 6 days (4 to 12).
Among the 240 patients, 18 (8%) did not have any follow-up visit (2 deaths), 17 (7%) had the 6-month follow-up visit only (4 deaths), and 15 (6%) the 12-month follow-up visit only. Therefore, 207 were followed up at 6 months and 205 at 12 months. Patients who were lost to follow-up did not significantly differ from those who had at least one visit, except that they had a lower education level (primary school: 29% versus 10%; P=0.02).
At 6 months, among the 205 patients who had been taking at least one drug, 169 (81%) were adherent to treatments. Among those who were not compliant, only 3 had stopped all treatments or missed tablets very regularly, admitting not to be convinced of the usefulness of their treatment. One hundred ninety-eight of 199 (99%) patients with ischemic stroke/TIA received at least one antithrombotic drug at 6 months and 192 of 200 (96%) at 12 months (one had deliberately stopped all treatments, one had hemorrhagic stroke during follow-up, one had not started his treatment again after tooth extraction, and the reason was unknown for the 5 other patients). Adherence to treatments was similar at 12 months (data not shown).
As shown in Table 2, BP did not change significantly between inclusion and the follow-up visits and between the 6-month and 12-month visits. The proportion of hypertensive patients with BP <140/90 mm Hg significantly increased between inclusion and the 6-month visit but remained unchanged thereafter. Less than 20% of patients with diabetes had their BP <130/80 mm Hg at all visits.
Table 3⇓ shows univariate analyses. In multivariate logistic regression, age (OR=0.64; 95% CI: 0.46 to 0.90 for 10 years of age), diabetes (OR=0.63; 0.26 to 1.51), BP <140/90 mm Hg at inclusion (OR=2.79; 1.32 to 5.88), intensification of treatment between the cerebrovascular event and inclusion (OR=2.44; 1.20 to 4.97; ie, mainly during hospitalization), and visit to a vascular neurologist between inclusion and the 6-month visit (OR=2.03; 0.93 to 4.43) were associated with BP control at 6 months. Patients who visited a vascular neurologist between inclusion and the 6-month visit had a nonsignificant greater decrease in systolic BP than those who did not (Δ=−4.9 versus +0.3; P=0.24). Multivariate linear regression showed that intensification of treatment between cerebrovascular event and inclusion (P=0.001) or between inclusion (P=0.04) and the 6-month visit (P=0.04) was positively associated with a decrease in systolic BP between inclusion and the 6-month visit, whereas there was a negative association with diabetes (P=0.001) and age (P=0.0002). Looking at the 12-month visit, age (OR=0.65; 0.46 to 0.93 for 10 years of age) and BP <140/90 mm Hg at 6 months (OR=6.17; 2.44 to 12.95) were associated with BP control. In multivariate linear regression, intensification of treatment between the 6- and 12-month visits (P=0.02) was positively and age (P=0.05) was negatively associated with a decrease in systolic BP between the 6- and 12-month visits.
Among patients with BP ≥140/90 mm Hg, at either visit, approximately 10% did not receive any antihypertensive agent and more than 20% received only one antihypertensive agent. Yet, only a minority (22 at 6 months and 25 at 12 months) of patients had resistant hypertension, ie, BP ≥140/90 mm Hg despite receiving ≥3 drugs, including at least one diuretic (Figure 2).16 At 6 months, only 44 of 96 (46%) of the patients with BP ≥140/90 mm Hg had their treatment reinforced (ie, adjunction of at least one antihypertensive drug) since the inclusion (Figure 3). Similarly, only 21 of 89 (24%) had their treatment reinforced after this visit. Patients with BP readings between 140/90 and 159/99 mm Hg were less likely to have their treatment reinforced at 6 months than those with higher BP (P=0.0002).
Finally, the results were similar when patients who had their BP ≥130/85 mm Hg at inclusion were also included or when analyses were restricted to patients with a known history of hypertension at the time of the qualifying event (data not shown).
In contrast to BP findings, there was a significant decrease in cholesterol levels between inclusion (ie, blood samples collected during hospitalization) and the 6-month follow-up visit (Table 2). However, no further decrease was observed thereafter. In patients with hypercholesterolemia, 73% had total cholesterol <2 g/L and 55% had LDL <1 g/L at 6 months. Those proportions were similar at 12 months. The use of statins had increased from 22% to 82% from the time of the cerebrovascular event and inclusion (P<0.0001), but remained unchanged thereafter.
Table 3 shows the univariate analyses. In multivariate analysis, factors associated with LDL <1 g/L were small vessel disease (OR=14.25; 2.72 to 74.58), LDL <1 g/L at inclusion (OR=7.17; 1.67 to 30.75), visit to a cardiologist between inclusion and the 6-month visit (OR=2.52; 1.03 to 6.16), knowledge of stroke/TIA diagnosis (OR=3.26; 0.89 to 11.90), addition of a statin agent during hospitalization (OR=3.36; 1.27 to 8.89), and persisting smoking at 6 months (OR=0.29; 0.08 to 1.04). Patients with small vessel disease stroke had similar baseline LDL level than patients with other subtypes of stroke (1.41±0.37 versus 1.33±0.45; P=0.24), but higher decrease in LDL (Δ=−0.61 g/L versus Δ=−0.27 g/L; P=0.0006). Multivariate linear regression showed that small vessel disease (P=0.004) and addition of a statin agent during hospitalization (P=0.0004) were positively associated with a decrease in LDL between inclusion and the 6-month visit. Persisting smoking was negatively associated with a decrease in LDL (P=0.04). The proportion of patients to whom statin was added during hospitalization differed across the different stroke subtypes: 76% in small vessel disease, 86% in large artery disease, 51% in cardioembolic, and 56% in undetermined (P=0.02). Among the 20 patients with LDL ≥1 g/L at 6 months who were not on statin agents, 4 (20%) were prescribed a statin agent between the 6- and 12-month visits.
Looking at the 12-month visit, addition of a statin agent during hospitalization (OR=13.31; 3.37 to 52.34) or between inclusion and the 12-month visit (OR=6.89; 1.17 to 40.66), LDL <1 g/L at inclusion (OR=5.98; 1.31 to 2.72), and hypertension (OR=2.34; 0.97 to 5.66) were associated with LDL <1 g/L. Results were similar when total cholesterol was used instead of LDL (data not shown).
Other Risk Factors
There was a decrease in the proportion of smokers and in that of excessive drinkers between the cerebrovascular event and the 6-month visit, but the proportion remained unchanged thereafter. All patients who declared they had given up smoking had low breath carbon monoxide levels. No patient started smoking. In multivariate analyses, factors associated with tobacco withdrawal were Rankin scale ≥1 (OR=2.18; 0.68 to 7.20), living with a partner or in a family (OR=4.23; 0.98 to 18.23), and hospitalization duration ≥7 days (OR=2.16; 0.66 to 7.12). At 6 months, 15 (7%) patients drank excessively (9 of them were already excessive drinkers at the time of their stroke/TIA). In multivariate analyses, factors associated with no or moderate alcohol consumption at 6 months were Rankin scale ≥1 (OR=2.52; 0.68 to 9.35), living with a partner or in a family (OR=4.66; 1.32 to 16.44), and female gender (OR=7.76; 0.95 to 63.59). There were too few patients with diabetes to analyze factors associated with control of HBA1c.
We have shown that, in a population of patients with stroke/TIA willing to take part in an observational study and who were adherent to treatments, more than 50% of patients with hypertension did not reach BP <140/90 mm Hg and 45% of patients with hypercholesterolemia did not reach LDL <1g/L at 6 months. Those proportions did not change at 12 months. In-hospital initiation or reinforcement of specific treatments strongly influenced control of and decrease in BP and LDL cholesterol. By contrast, patient-related factors such as sociodemographic characteristics, knowledge of disease or risk factors, psychological status, and associated diseases had little influence. Moreover, approximately 40% of patients with elevated BP during follow-up received either no treatment or a monotherapy. Yet, it is well recognized that most patients need more than one agent to effectively reduce their BP.16 Only 25% of patients had their treatment reinforced thereafter despite not having achieved BP therapeutic goals. Similarly, 20% of those who had an elevated LDL cholesterol level at 6 months were prescribed statin agents thereafter. This phenomenon is called “clinical” or “therapeutic” inertia.29,30
Therapeutic inertia has been identified as one of the strongest determinants for not achieving standard-of-care goals in hypertension, elevated LDL cholesterol levels, and diabetes in other populations.30 The small proportion of patients for whom treatment was reinforced, despite documented persistently high BP found in our study (40%), was very similar to that found in 2 previous studies conducted in hypertensive patients.29,31 In the first study, the most frequently cited reason for no initiation or change in therapy was related to primary care physicians being satisfied with the BP value.31 Interestingly, in keeping with the results of the second study,29 we observed that patients with BP readings in the stage 1 (ie, between 140/90 and 159/99 mm Hg) were less likely to have their treatment reinforced as compared with those with higher BP. Like in the latter study, the majority of individuals with uncontrolled hypertension were within 10/5 mm Hg of the goal BP. It has been estimated that an absolute improvement of 20% in the percentage of visits accompanied by intensification of therapy could improve control rate from 46% to 66%.29 Similarly, we found that 45% of patients had their LDL above the recommended level at 6 months and that a minority of those who had an elevated LDL cholesterol level at 6 months were prescribed statin agents thereafter. We found that patients with small vessel disease had a significantly greater subsequent decrease in LDL than those with other stroke subtypes. We may speculate that clinicians were more prone to initiate treatment and/or to use higher doses of statins due to slightly higher, although nonsignificant, baseline cholesterol levels in those patients.
Causes of therapeutic inertia are not well known. It could result from overestimation of care provided, use of “soft” reasons to avoid intensification of therapy (perception that control is improving, potential side effects, concerns about whether results from large trials can legitimately guide individual decisions, and so on), and lack of education, training, and practice organization focused on achieving therapeutic goals.30 Although physicians have relatively good knowledge of what should be done according to guidelines, they have not necessarily been trained in achieving goals (use of multidrug therapies and high dosages) and often lack of organizational resources. We did not collect detailed data on physicians such as knowledge of therapeutic goals or attitude toward guidelines, which may have influenced therapeutic inertia. However, to date, such factors still remain difficult to assess.32
As noticed in previous studies conducted in patients with stroke33 or coronary artery disease,34 we found that in-hospital initiation of preventive therapies was associated with higher treatment rates during follow-up and consequently with better risk factors control. Such a strategy may theoretically help to alleviate patients’ concerns regarding side effects, conveys the message that therapies are essential for the prevention of recurrent events, and seems to improve long-term patient adherence.34
Our study has several strengths. First, we selected relatively homogeneous patients for whom secondary prevention was indisputably justified according to guidelines. We did not include elderly people because there is no consensus on the best prevention strategies in those patients, who are rarely enrolled in therapeutic trials and less prepared to take part in observational studies. Second, there was an independent and standardized assessment of the quality of stroke secondary prevention. Third, we recorded many potential determinants for stroke prevention implementation. In particular, we collected therapeutic changes, which, to our knowledge, had not yet been performed to date.
There are also several limitations to our study. First, the high rate of refusal may question the generalizability of our results. However, nonparticipants had fairly similar general characteristics and therapeutic inertia was unlikely to be less frequent in those patients. At most, we may have underestimated some patient-related factors such as adherence to treatments. Because few low-educated patients were enrolled, we may also have underestimated the impact of socioeconomic factors.35 The low participation also underlines difficulties in carrying out quality of care assessment in large representative populations. Second, because we enrolled fewer patients than expected, our analyses lacked power to detect factors less frequent and/or associated with smaller effect. However, the rates of uncontrolled BP and cholesterol (≥40%) were higher than expected, which has increased the a posteriori statistical power. Third, although we measured BP as strictly as we could, we may have underestimated BP variability, in particular variability related to the white coat effect. However, except for specific situations, office BP measurement remains the gold standard method to detect hypertension and assess the response to treatment.16,36 Moreover, it has been shown that the difference in BP control between clinic and home assessment is small37 and that high BP values commonly found in treated hypertensive individuals cannot be accounted for by white coat effect.38 Fourth, because data on adherence to treatments were obtained from patients’ declarations, there is a possibility of inaccuracy. However, there is no available objective observance test for all therapies. Moreover, patient nonadherence does not seem to explain therapeutic inertia.30 Finally, our study design did not allow to assess whether the patient has any role in therapeutic inertia, although this phenomenon is more likely to result from physicians’ attitudes than from patients’ attitudes.
There are several practical implications to our results. First, our findings show that therapeutic inertia is as prevalent in stroke secondary prevention as in primary prevention and it prompts us to develop specific strategies to reduce this inertia.31 Second, they show that initiation of preventive therapies before hospital discharge results in a marked increase in BP and cholesterol levels control, prompting us to develop and evaluate widespread specific hospital-based interventions to achieve therapeutic goals shortly after a cerebrovascular event.
Appendix 1: List of Participants
Hôpital Cochin: Jamal Kansao, Christine Ginsburg, Yann-Erick Claessens, Khalil Takun, Guillaume Der Sahakian, François Lecomte, Franck Perruchet, and Roger Ranerison. Hôpital Européen Georges–Pompidou: Rafik Masmoudi, Albert Levy, Nicole Sembach, Pierrre Meraud, Marie-Pierre Sadier, Trung-Ha Cao, Athanassia Gounaropoulos, Henri-Mehdi Salahshour, and Alain Davido. Hôpital Bicêtre: Benoît Doumenc, André Ferreira, Fatima Brahimi, Jacqueline Depret-Vassal, David Adams, and Enrique Casalino.
Appendix 2: Five-Point Shea Adherence Score
Do you ever forget to take your pills?
Are you ever careless in taking your pills?
Do you ever miss taking your pills when you are feeling better?
Do you ever miss taking any of your pills because you are feeling sick?
Do you ever miss taking your pills?
We thank Frédérique Accolas and Isabelle Laurent for help with collecting data. We thank Sabine Helfen and Caroline Maquet for help with the data management and all the staff of the Unité de Recherche Clinique, Paris Centre, APHP, Paris, France. We also thank Marie-Liesse Piketty (Hôpital Sainte-Anne, Paris) for her help with blood sample analyses.
Source of Funding
This study was funded by Servier Medical, which had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
- Received August 28, 2007.
- Revision received October 14, 2007.
- Accepted October 30, 2007.
Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006; 37: 577–617.
Touzé E, Varenne O, Chatellier G, Peyrard S, Rothwell PM, Mas JL. Risk of myocardial infarction and vascular death after transient ischemic attack and ischemic stroke: a systematic review and meta-analysis. Stroke. 2005; 36: 2748–2755.
Holloway RG, Benesch C, Rush SR. Stroke prevention: narrowing the evidence-practice gap. Neurology. 2000; 54: 1899–1906.
Amar J, Cambou JP, Touzé E, Bongard V, Jullien G, Vahanian A, Coppe G, Mas JL. Comparison of hypertension management after stroke and myocardial infarction: results from ECLAT1—a French nationwide study. Stroke. 2004; 35: 1579–1583.
Joseph LN, Babikian VL, Allen NC, Winter MR. Risk factor modification in stroke prevention. The experience of a stroke clinic. Stroke. 1999; 30: 16–20.
Mouradian MS, Majumdar SR, Senthilselvan A, Khan K, Shuaib A. How well are hypertension, hyperlipidemia, diabetes, and smoking managed after a stroke or transient ischemic attack? Stroke. 2002; 33: 1656–1659.
Touzé E, Mas JL, Rother J, Goto S, Hirsch AT, Ikeda Y, Liau CS, Ohman EM, Richard AJ, Wilson PW, Steg PG, Bhatt DL. Impact of carotid endarterectomy on medical secondary prevention after a stroke or a transient ischemic attack: results from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Stroke. 2006; 37: 2880–2885.
Filippi A, Bignamini AA, Sessa E, Samani F, Mazzaglia G. Secondary prevention of stroke in Italy: a cross-sectional survey in family practice. Stroke. 2003; 34: 1010–1014.
Hillen T, Dundas R, Lawrence E, Stewart JA, Rudd AG, Wolfe CDA. Antithrombotic and antihypertensive management 3 months after ischemic stroke. A prospective study in an inner city population. Stroke. 2000; 31: 469–475.
Sappok T, Faulstich A, Stuckert E, Kruck H, Marx P, Koennecke HC. Compliance with secondary prevention of ischemic stroke. A prospective study. Stroke. 2001; 32: 1884–1889.
Touzé E, Cambou JP, Ferrieres J, Vahanian A, Coppe G, Leizorovicz A, Jullien G, Guerillot M, Herrmann MA, Mas JL. Antithrombotic management after an ischemic stroke in French primary care practice: results from three pooled cross-sectional studies. Cerebrovasc Dis. 2005; 20: 78–84.
Grol R. Successes and failures in the implementation of evidence-based guidelines for clinical practice. Med Care. 2001; 39: II-46–II-54.
Grol R. Beliefs and evidence in changing clinical practice. BMJ. 1997; 315: 418–421.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42: 1206–1252.
Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke. 2003; 34: 2741–2748.
Steiner T, Kaste M, Forsting M, Mendelow D, Kwiecinski H, Szikora I, Juvela S, Marchel A, Chapot R, Cognard C, Unterberg A, Hacke W. Recommendations for the management of intracranial haemorrhage—part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis. 2006; 22: 294–316.
Wolf PA, Clagett GP, Easton JD, Goldstein LB, Gorelick PB, Kelly-Hayes M, Sacco RL, Whisnant JP. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack. A statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 1999; 30: 1991–1994.
O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ. 2001; 322: 531–536.
Williams LS, Bruno A, Rouch L, Mariott DJ. Stroke patients knowledge of stroke. Influence on time to presentation. Stroke. 1997; 28: 912–915.
Agence Nationale d’Accréditation et d’Evaluation en Santé. Prise en charge des patients adultes atteints d’hypertension artérielle. Paris: Agence Nationale d’Accréditation et d’Evaluation en Santé; 2000.
Agence française de sécurité sanitaire des produits de santé. Prise en charge thérapeutique du patient dyslipidémique. Paris: Agence française de sécurité sanitaire des produits de santé; 2005.
Okonofua EC, Simpson KN, Jesri A, Rehman SU, Durkalski VL, Egan BM. Therapeutic inertia is an impediment to achieving the Healthy People 2010 blood pressure control goals. Hypertension. 2006; 47: 345–351.
Touzé E, Saillour-Glenisson F, Durieux P, Verdier A, Leyshon S, Bendavid S, Attard T, Scheimann A, Mas JL, Coste J. Lack of validity of a French adaptation of a scale measuring attitudes towards clinical practice guidelines. Int J Qual Health Care. 2006; 18: 195–202.
Ovbiagele B, Saver JL, Fredieu A, Suzuki S, Selco S, Rajajee V, McNair N, Razinia T, Kidwell CS. In-hospital initiation of secondary stroke prevention therapies yields high rates of adherence at follow-up. Stroke. 2004; 35: 2879–2883.
Fonarow GC. The role of in-hospital initiation of cardiovascular protective therapies to improve treatment rates and clinical outcomes. Rev Cardiovasc Med. 2003; 4 (suppl 3): S37–S46.
Lang T. Social and economic factors as obstacles to blood pressure control. Am J Hypertens. 1998; 11: 900–902.
Cappuccio FP, Kerry SM, Forbes L, Donald A. Blood pressure control by home monitoring: meta-analysis of randomised trials. BMJ. 2004; 329: 145.