Article Text

Research paper
Secondary prevention in patients with vascular disease. A population based study on the underuse of recommended medications
  1. Yannick Béjot1,
  2. Marianne Zeller2,
  3. Luc Lorgis2,
  4. Odile Troisgros3,
  5. Corine Aboa-Eboulé1,2,
  6. Guy-Victor Osseby1,
  7. Maurice Giroud1,
  8. Yves Cottin1
  1. 1Department of Neurology, Dijon Stroke Registry, EA4184, Medical School and University Hospital of Dijon, University of Burgundy, Dijon, France
  2. 2Observatoire des Infarctus de Côte-d'Or (RICO), LPPCE, IFR Santé-STIC, University of Burgundy, University of Hospital and Medical School of Dijon, Dijon, France
  3. 3Department of Rehabilitation, University Hospital of Dijon, Dijon, France
  1. Correspondence to Dr Y Béjot, Department of Neurology, Service de Neurologie, Dijon Stroke Registry, Hôpital Général, 3 Rue du Faubourg Raines, Dijon 21033, France; ybejot{at}yahoo.fr

Abstract

Objectives To investigate the premorbid use of secondary prevention medications in patients with recurrent vascular events.

Design Prospective, observational, population based study.

Setting The Dijon Stroke Registry and the registry of myocardial infarction of Dijon and Côte d'Or, France.

Patients All patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attacks) or coronary artery disease (CAD) and a history of vascular disease (cerebral ischaemia, CAD or peripheral arterial disease (PAD)) in Dijon, France from 2006 to 2010.

Main outcome measures Data on medical history and prior use of treatments were collected. Mutivariate analyses were performed to identify predictors of the use of medications.

Results 867 patients (614 cerebral ischaemia and 253 CAD) were recorded including 448 (51.7%) with a history of cerebral ischaemia only, 191 (22.0%) with a history of CAD only, 68 (7.8%) with a history of PAD only and 160 (18.5%) with a history of polyvascular disease. In these 867 patients, 57.3% were on antithrombotic therapy, 61.2% were treated with antihypertensive drugs, 32.9% received statins and only 23.6% were on an optimal regimen, defined as a combination of the three therapies. Compared with patients with previous CAD only, those with previous cerebral ischaemia only were less likely to be receiving each of these treatments or to receive an optimal regimen (OR=0.17, 95% CI 0.14 to 0.26, p<0.001).

Conclusions Our findings underline the fact that the underuse of secondary preventive therapies is common in patients with recurrent vascular events, especially those with previous cerebral ischaemia. This underuse could be targeted to reduce recurrent vascular events.

  • Stroke

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Introduction

Atherothrombosis is the underlying pathophysiological mechanism shared by coronary artery disease (CAD), cerebral ischaemia and peripheral arterial disease (PAD).1 ,2 Over the past few years, there has been convincing evidence from randomised clinical trials that several classes of medications are greatly effective in reducing the risk of recurrent events in patients with vascular disease. As a result, guidelines for secondary prevention have been established.3–6 They indicate that a combination of antithrombotic therapy, statins and blood pressure lowering treatment is the optimal regimen to avoid recurrent events in patients with vascular disease. However, several studies have pointed out that a gap between clinical practice and evidence based recommendations may exist.7–21

In this prospective population based study from two large contemporary registries, we aimed to investigate the current use of secondary prevention medications in patients presenting with a recurrent vascular event in order to provide a clear representation of the impact of the underuse of secondary prevention drugs on the burden of vascular disease.

Methods

This study was based on data prospectively obtained from 1 January 2006 to 31 December 2010 from the DIjon VAscular (DIVA) project, whose methodology has been described elsewhere.22 ,23 Briefly, the DIVA project aims to cross data from the Dijon Stroke Registry with that from the registry of myocardial infarction of Dijon and Côte d'Or (RICO) in order to identify all patients with either first ever or recurrent cerebral ischaemia or CAD, in the city of Dijon, France (152 000 inhabitants according to the 2006 census).

Case ascertainment

The methodology of the Dijon Stroke Registry for their collection procedure relies on multiple overlapping sources of information to identify both incident and recurrent fatal and non-fatal strokes and transient ischaemic attacks (TIA) in hospitalised and non-hospitalised patients22–24: (1) emergency rooms, and all clinical and radiological departments of Dijon University Hospital and the three private hospitals in the city and its suburbs; (2) patient's home or nursing home, with diagnosis assessed by general practitioners helped by public or private neurologists from outpatient clinics; (3) medical records of radiological and Doppler ultrasound centres; (4) and death certificates obtained from the local Social Security Bureau that is responsible for the registration of deaths in the community, particularly fatal strokes outside of hospital. The diagnosis of stroke subtype was always made on clinical examination, cerebral imaging and complementary examinations. For this study, we only included patients with a diagnosis of cerebral ischaemia (either ischaemic stroke or TIA), defined according to WHO recommendations.25

The design and methods of the population based RICO registry have been described elsewhere.22 ,23 ,26 Briefly, the RICO registry collects data from all patients with acute myocardial infarction (MI) in the private or public centres of one French region (Côte d'Or), including Dijon. For the DIVA project, only MI patients residing in Dijon were considered. Both ST elevation MI and non-ST elevation MI were included in the DIVA project. Data were collected at each site by a study coordinator trained in completing the core record form and in extracting data from medical records, using a standardised case report form.

Collection of vascular risk factors

Prior to event vascular risk factors were collected at the time of inclusion of patients in the registries, using patients’ self-reports, and hospital and general practitioners’ records, with a common methodology, as previously described.22 ,23 Hypertension was defined by a history of known hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) or antihypertensive treatment. Diabetes mellitus was recorded if a glucose level of ≥7.8 mmol/l had been reported in the medical records or if the patient was on insulin or oral hypoglycaemic agents. Hypercholesterolaemia was defined as a total cholesterol level of ≥5.7 mmol/l. We also recorded smoking (current or former habit), and a history of atrial fibrillation.

For each patient, vascular history including cerebral ischaemia (either ischaemic stroke or TIA), CAD (MI, unstable angina, coronary artery bypass graft or percutaneous coronary intervention) and PAD (prior intermittent claudication, critical lower limb ischaemia or vascular surgery) was collected. As our objective in this study was to evaluate secondary prevention, we only included patients with a history of vascular disease.

The use of medications prior to inclusion was recorded by interview of the patients, their relatives or their care providers: antithrombotic therapy (aspirin, clopidogrel, dipyridamole, ticlopidine or vitamin K antagonists), blood pressure lowering therapy (β blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonist, calcium antagonists or diuretics) and statins. Optimal therapy was defined by the association of antithrombotic therapy, blood pressure lowering therapy and statins, as recommended by several professional bodies.3–6 Missing data on vascular risk factors and treatments were less than 0.5%, except for smoking status (2.5%).

Statistical analysis

Proportions and mean values for baseline characteristics were compared between groups using the χ2 test and analysis of variance, when appropriate. A Bonferroni correction was used for multiple comparisons. Predictors of the use of antithrombotic therapy, antihypertensive drugs, statins and optimal regimen were analysed using multivariate logistic regression to obtain OR and 95% CI. In the models, we introduced age, sex, prior atrial fibrillation, diabetes, type of previous cardiovascular disease and treatments. Age as a variable that did not satisfy the log linearity assumption was included in the models as a stratified variable. Post hoc analyses were performed by subgroups according to the nature of the history of vascular disease (previous cerebral ischaemia or previous CAD). Statistical analysis was performed with STATA V.9.0 software and a level of α=0.05 was used to evaluate the results.

Ethics

The Dijon Stroke Registry and RICO survey were both approved by the National Ethics Committee (CNIL), and Dijon Stroke registry was also approved by the French Institute for Public Health Surveillance (InVS).

Results

Over the 5 year study period, 867 patients (614 with cerebral ischaemia including 283 (46.1%) TIA, 331 (53.9%) ischaemic stroke and 253 with CAD) with a history of vascular disease were recorded. The distribution of previous vascular diseases was as follows: 448 (51.7%) had a history of cerebral ischaemia only, 191 (22.0%) had a history of CAD only, 68 (7.8%) had a history of PAD only and 160 (18.5%) had a history of at least two vascular diseases (polyvascular disease). In the latter group, 68 (47.6%) patients had a history of both cerebral ischaemia and CAD, 49 (30.6%) had a history of both CAD and PAD, 26 (18.2%) had both prior cerebral ischaemia and PAD and 17 (10.6%) had a history of cerebral ischaemia, CAD and PAD. Of note, recurrent events were most frequently observed in the same organ as the first event (figure 1). The characteristics of patients according to their past vascular disease are shown in table 1.

Table 1

Characteristics of patients according to their history of vascular disease

Figure 1

Distribution of previous vascular events in included patients with cerebral ischaemia or coronary artery disease. CAD, coronary artery disease; PAD, peripheral arterial disease.

Among the 867 patients with a history of CAD and/or cerebral ischaemia and/or PAD, 497 (57.3%) were receiving antithrombotic therapy, 531 (61.2%) were being treated with an antihypertensive drug and less than a third (285, 32.9%) were receiving statins. Moreover, only 205 (23.6%) were on an optimal regimen, defined as a combination of one antithrombotic agent, one antihypertensive drug and one statin. However, great discrepancies in the frequency of the use of preventive therapies were found between patients according to their past history of vascular diseases (table 1, figure 2). Patients with previous cerebral ischaemia only were least likely to receive a secondary prevention drug, whereas patients with previous CAD only were most likely to receive these drugs, whatever drug was considered. Only 10.5% of cerebral ischaemia patients, but 44% of CAD only patients, 26.5% of PAD only patients and 35% of those with polyvascular disease, were receiving the optimal regimen. Of note, a higher proportion of patients with previous cerebral ischaemia only were on antithrombotics (50.8% vs 37.2%), statins (24.9% vs 16.5%) and optimal regimen (13% vs 6.7%) during the period 2009–2010 compared with the period 2006–2008 (see online supplementary table S1). Similar improvements with time in the use of statins and optimal therapy were noted in patients with polyvascular disease, whereas no change was observed in those with previous CAD or previous PAD only.

Figure 2

Proportion of the use of preventive medications according to the history of vascular disease. Bars represent 95% CI. CAD, coronary artery disease; PAD, peripheral arterial disease.

In multivariate analyses of predictors of the use of preventive therapy in patients with previous vascular disease, prior cerebral ischaemia was associated with a lower frequency of the use of antithrombotic therapy, antihypertensive drugs, statins and optimal therapy, compared with patients with a history of CAD only (table 2). Similarly, the use of statins and an optimal regimen were significantly lower in patients with prior PAD. Male gender was associated with an increased use of antithrombotic treatment, diabetes was an independent predictor of antihypertensive drug use and prior atrial fibrillation was associated with a greater use of antithrombotic therapy and a lower use of statins. The use of optimal therapy was more frequent in male patients and in those with diabetes. In addition, using one preventive treatment was predictive of using a second one.

Table 2

Mulivariate analyses of predictors of the use of preventive therapy in patients with previous vascular events

In post hoc analyses, in patients with a history of cerebral ischaemia, associated CAD was predictive of the use of antithrombotic therapy, statins and the optimal regimen (table 3). In addition, age >60 years and diabetes were both associated with an increased use of antihypertensive drugs. In patients with a history of CAD, only male sex (OR=2.52; 95% CI 1.50 to 4.23, p<0.001) and diabetes (OR=2.14; 95% CI 1.29 to 3.57, p=0.023) were associated with the use of the optimal regimen (data not shown).

Table 3

Mulivariate analyses of predictors of the use of preventive therapy in patients with history of cerebral ischaemia

Discussion

Conducting a large population based study from contemporary data of two regional registries, we demonstrated that patients currently presenting with either CAD or cerebral ischaemia, and who had a medical history of vascular disease, were markedly undertreated by recommended preventive therapies. Indeed, less than a quarter of patients were on an optimal regimen. This under utilisation was particularly marked in patients with previous cerebral ischaemia, despite some improvements with time.

Our results are consistent with those from previous studies that focused on the gap between evidence based medicine and real world clinical practice,9 ,10 ,13 ,14 ,17 ,18 and several explanations could account for the underuse of preventive drugs, including inadequate prescription of these therapies after an initial event, possibly due to variations in the application of the guidelines according to the management of patients (general practitioners vs hospital doctors) or poor adherence to the prescribed regimen,8 ,13–17 despite some improvement in recent years.17 ,18 In our study, only 23% of patients were currently on the recommended triple medication.3–6 This rate is much lower than that reported by previous studies, and methodological differences could account for this result as we included patients with either recurrent CAD or cerebral ischaemia in whom preventive therapies had obviously failed.

Another interesting finding of the present study is the great difference between patients with previous CAD and those with previous cerebral ischaemia in the use of preventive therapy. A similar trend was found in a study based on two national registries involving primary care physicians, which demonstrated that optimal care was more frequently achieved in patients with CAD than in those with cerebral ischaemia.9 ,21 The reasons for such discrepancies remain hypothetical. On the one hand, although the effectiveness of both antithrombotic and antihypertensive drugs has been established for many years, the benefit of statins in the secondary prevention of cerebral ischaemia has been shown more recently.27 Changing medical practice requires time, which could explain why statins were the least likely to be used in patients with prior cerebral ischaemia only (20% of patients), and why we noticed an improvement with time. On the other hand, the fact that less than one in two patients were on antithrombotic or antihypertensive drugs after cerebral ischaemia is more worrying and questionable, and explanations for such a finding remain speculative. It could be that patients suffering a TIA or a minor stroke may receive less medical attention, leading to the underuse of secondary prevention, compared with that observed in CAD patients. This assumption is supported by the fact that the use of antithrombotic agents, antihypertensive drugs and the optimal regimen was greater in patients with history of cerebral ischaemia plus CAD than in those with prior cerebral ischaemia only (table 3). Another potential explanation is that patients with cerebral ischaemia are at a high risk of cognitive impairment and dementia,24 ,28 which could affect their adherence to treatment, or the prescription of ‘aggressive’ treatments to such patients by practitioners. Further work is needed to explore this issue.

The major strength of this study is the prospective population based design, which ensured the exhaustiveness of case ascertainment of patients with either CAD or cerebral ischaemia. Hence in our study on current daily clinical practice, we provided a clear and contemporary representation of the burden engendered by the under utilisation of preventive therapy in patients presenting with a recurrent vascular event. We compared prevention measures between two time periods, and showed a clear improvement. However, several possible limitations must be acknowledged. Firstly, this study was conducted in patients with a recurrent vascular event only—that is, those who experienced a failure of secondary prevention. This prevents us from generalising our findings to all patients with a history of vascular disease. Nevertheless, we think that this investigation is clinically relevant as it will help understand the potential contributors to vascular event recurrence. Secondly, the reasons for not using preventive treatments were not investigated, in particular because there was insufficient information about the type of attending clinician after the initial vascular event, and adherence of patients to their treatment was not assessed. Thirdly, there was no evaluation of the achievement of target prevention in patients actually receiving adequate treatments, and consequently we may have overestimated the true effectiveness of secondary prevention in these patients. Fourthly, the delay between the diagnosis of the first vascular disease and the recurrent event was not obtained, which is important as the patient's adherence to treatment may decrease over time.13 Moreover, reasons for not using treatments were not collected.

In conclusion, our findings underline the fact that the underuse of secondary preventive therapies is common in patients with recurrent vascular events, especially those with previous cerebral ischaemia. This underuse could be targeted to reduce the recurrence of vascular events.

Acknowledgments

We thank Mr Philip Bastable for reviewing the English language, the French Institute for Public Health Surveillance (InVS) and INSERM.

References

Supplementary materials

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Footnotes

  • Contributors All authors contributed to the article by participating in conception and design (YB, MZ, MG, YC), acquisition of the data (YB, MZ, LL, OT, G-VO, MG, YC) or analysis and interpretation of the data (YB, MZ, CA-E, MG, YC), drafting the article (YB, MZ) or revising it critically for important intellectual content (LL, OT, CA-E, G-VO, MG, YC), and approving the final manuscript (all authors).

  • Funding The Dijon Stroke Registry is supported by the French Institute for Public Health Surveillance (InVS) and INSERM. The observatoire RICO is supported by the University Hospital of Dijon, Association de Cardiologie de Bourgogne, Conseil Régional de Bourgogne, Fédération Française de Cardiologie and by grants from the Agence Régionale de Santé (ARS) de Bourgogne. The study sponsors had no role in the study design, collection, analysis and interpretation of the data, writing of the report or in the decision to submit the paper for publication.

  • Competing interests YB received financial support from the Journées Neurologiques de Langue Française and the Regional Council of Burgundy.

  • Ethics approval The Dijon Stroke Registry and RICO survey were both approved by the National Ethics Committee (CNIL). The Dijon Stroke Registry was also approved by the French Institute for Public Health Surveillance (InVS)

  • Provenance and peer review Not commissioned; externally peer reviewed.

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