1 ARTIGOS ORIGINAIS CONCISOS Impact of a Structured Intensive Follow-up Program on the Control of Hypertension in Coronary Patients a Randomized Trial  PEDRO S. MATEUS, NUNO BETTENCOURT, CARLA COSTA DIAS, LINO SANTOS, LUÍS ADÃO, JOSÉ ROBERTO, CARLOS MATEUS, JOSÉ RIBEIRO, JOÃO PRIMO, LINO SIMÕES, VASCO GAMA RIBEIRO, HENRIQUE BARROS Cardiology Department, Vila Nova de Gaia Hospital Centre, Vila Nova de Gaia, Portugal Epidemiology Department, University of Porto, Medical School, Porto, Portugal Rev Port Cardiol 2005; 24(2): ABSTRACT Introduction: Hypertension is an important risk factor for cardiovascular events. Although several anti-hypertensive agents have shown to be effective in the treatment of hypertension, adequate blood pressure control is not frequent in most populations. The aim of this study was to evaluate the effect of a structured intensive follow-up program (SIFUP) on the control of blood pressure in coronary patients. Patients and Methods: we performed a prospective, randomized study including 237 patients admitted to the Cardiology Department for acute coronary syndrome. Patients were randomly assigned to a SIFUP (n=129) or to the general cardiology outpatient department (COD) (n=108). An experienced doctor performed a blind assessment of blood pressure in 157 randomised patients, 9 to 18 months after discharge. In statistical analysis, the chisquare test was used to compare proportions and the Student s t test to compare means. Results: Both groups were predominantly male and mean age was similar. The proportion of patients with known hypertension randomised to the SIFUP and the COD did not differ. At the 9 to 18-month assessment there was no statistical significant difference in the proportion of patients with blood pressure under target values (57.5% in SIFUP and 48.5% in COD, p=ns). However, in hypertensive patients, the proportion of controlled patients was significantly higher in the SIFUP than in the COD (44.8% vs. 24.2%, p=0.05) and systolic and mean blood RESUMO Impacto de um Programa Estruturado de Seguimento Intensivo no Controlo da Hipertensão em Doentes Coronários um Ensaio Randomizado Introdução: A hipertensão arterial é um importante factor de risco para eventos cardiovasculares. Embora existam variados fármacos eficazes no tratamento da hipertensão, verifica-se um controlo inadequdo da pressão arterial na maioria das populações. O objectivo deste estudo foi avaliar o impacto de um Programa Estruturado de Seguimento Intensivo (PESI) no controlo da pressão arterial em doentes coronários. Pacientes e Métodos: Foi efectuado um estudo prospectivo, aleatorizado, incluindo 237 doentes internados no Serviço de Cardiologia por Síndrome Coronário Agudo. Na data de alta, os doentes foram referenciados, de forma aleatória, ao PESI (n = 129) ou à Consulta Externa de Cardiologia (CEC) (n = 108). Um médico efectuou a avaliação da pressão arterial entre 9 e 18 meses após a alta hospitalar em 157 pacientes, com ocultação para o resultado da aleatorização. Foi utilizado o teste do qui-quadrado na comparação de proporções e o teste t de Student na comparação de variáveis contínuas. Resultados: Verificou-se, nos dois grupos, uma proporção mais elevada de doentes do sexo masculino; não foram encontradas diferenças na média etária. A proporção de doentes com hipertensão arterial conhecida não foi significativamente diferente entre o 223 Recebido para publicação: Agosto de 2004 Aceite para publicação: Novembro de 2004 Received for publication: August 2004 Accepted for publication: November 2004
2 Rev Port Cardiol Vol. 24 Fevereiro 05/ February 05 pressure were significantly lower in the SIFUP (respectively vs mmhg, p=0.04 and 98.7 vs mmhg, p=0.03); diastolic blood pressure was also lower in SIFUP (78.5 vs mmhg, p=ns). Conclusions: The SIFUP has shown to be effective in lowering blood pressure in hypertensive coronary patients. The proportion of patients with controlled blood pressure was consistently higher in the SIFUP. PESI e a CEC. Na avaliação efectuada entre os 9 e 18 meses após a alta, não foram demonstradas diferenças estatisticamente significativas na proporção de doentes com valores de pressão arterial inferiores aos recomendados (57,5 % no PESI e 48,5 % na CEC, p = ns). No entanto, considerando apenas os doentes com hipertensão conhecida, a proporção de doentes com pressão arterial controlada foi significativamente mais elevada no PESI do que na CEC (44,8 % vs 24,2 %, p= 0,05) e a pressão arterial sistólica e média foi também significativamente menor no PESI do que na CEC (respectivamente 139,0 vs 148,8 mmhg, p = 0,04 e 98,7 vs 103,9 mmhg, p = 0,03); a pressão arterial diastólica foi também menor no PESI (78,5 vs 81,5 mmhg, p = ns). Conclusões: O PESI demonstrou ser eficaz na obtenção de uma redução adicional da pressão arterial em doentes coronários com hipertensão. A proporção de doentes com pressão arterial controlada foi consistentemente mais elevada no PESI. Key wordse Hypertension; Blood pressure; Myocardial infarction; Unstable angina; Follow-up; Randomized trial Palavras-chave Hipertensão; Pressão arterial; Enfarte do miocárdio; Angina instável; Seguimento; Ensaio randomizado 224 INTRODUCTION Hypertension is an important risk factor for cardiovascular events; several trials of anti-hypertensive agents have shown that treatment of hypertension reduces the morbidity and mortality associated with high blood pressure (1, 2). Nevertheless, adequate blood pressure control is poor in most populations; the best results have been reported in the United States of America, indicating that only about 34% of hypertensive patients were controlled in (3). In European countries, the proportion of patients with properly controlled blood pressure was even lower (4, 5). Moreover, the treatment goals recommended by recent guidelines are increasingly strict, particularly in patients with diabetes or renal disease (3, 6). Patients with high cardiovascular risk, such as those who have suffered an acute coronary syndrome, are also an important population that needs intensive management of high blood pressure. International scientific societies have provided guidelines about life-style modification and pharmacological treatment of arterial hypertension, but little attention has been given to the patient s follow-up methods. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that follow-up should be performed on a monthly basis until blood pressure control is achieved, and thereafter one follow-up visit every 3 to 6 months should be adequate (3). The British Society of Hypertension and Canadian consensus guidelines suggest similar follow-up periods. However, these recommendations are only based on non-controlled studies and there is a clear absence of evidence that different intervals and methods of follow-up could influence blood pressure control. The Cardiology Department of The Vila Nova de Gaia Hospital Centre has set up a Structured Intensive Follow-up Program of patients admitted in this department for acute coronary syndrome, to improve control of cardiovascular risk factors and achieve better long-term results in this high-risk population.
3 So, the aim of present study was to evaluate, in these patients, the effectiveness of this Intensive Follow-up Program in the long-term control of blood pressure, in comparison with standard care in the outpatient department. METHODS The study was conducted in the Cardiology Department of the Vila Nova de Gaia Hospital Center. Recruitment of patients began after approval of the research protocol by the institution s Ethics Committee. Informed consent was obtained from patients enrolled in the study. Study Population Patients admitted for acute coronary syndrome to the Cardiology Department between July 2001 and December 2002 were eligible to participate in the study. Exclusion criteria were previous follow-up in a cardiology or internal medicine clinic, even in the same hospital, in-hospital fatal myocardial infarction or significant non-cardiovascular comorbidity that precluded a 9 to 18-month follow-up. Patients could not be excluded on the basis of age or gender. In this period, 509 patients were admitted to the Cardiology Department for acute coronary syndrome. At hospital discharge, 237 patients were enrolled in the study. Randomization Patients enrolled in the study were randomly assigned to a structured intensive follow-up program (SIFUP 129 patients) or referred for usual follow-up in the cardiology outpatient department (COD 108 patients). Two patients (one from each group) decided after randomization to have their follow-up visits in another cardiology clinic and were therefore excluded from the data analysis. PEDRO S. MATEUS, et al Rev Port Cardiol 2005; 24: In the COD group, the frequency of appointments, diagnostic procedures and prescription of treatments was left entirely at the consulting cardiologist s discretion. Psychiatric counseling was available for SI- FUP patients and appointments with a nutritionist were possible in both groups. Outcome assessment A clinical examination, performed by a doctor with experience in cardiology, blinded to the randomization result, was planned for 9 to 18 months after hospital discharge. The objectives of this assessment were evaluation of cardiovascular symptoms, of physical examination signs and compliance with treatment. During this clinical evaluation, blood pressure measurement with a mercury sphygmomanometer was performed twice, in the sitting position, after 5 minutes of rest. An interval of 5 minutes or more was observed between the first and the second measurement. An adequate evaluation of blood pressure was possible in 157 patients. Mean blood pressure was computed using the formula (2x diastolic blood pressure+systolic blood pressure)/3. The mean of the two measurements of systolic and diastolic blood pressure was used in the data analysis. Normal and target blood pressure values for hypertensive patients were defined according to the most recent recommendations of the European Society of Hypertension (6). Blood pressure control was considered adequate when blood pressure was lower than 140/90 mmhg in nondiabetic patients and below 130/80 mmhg in patients with diabetes. Statistical analysis Statistical analysis was performed using SPSS for Windows. In the comparison of means between SIFUP and COD the Student s t test was used. The proportions of patients with normal values and controlled blood pressure were computed and the chi-square test was used to compare proportions. Follow-up groups The SIFUP consisted of pre-determined appointments at 1 week after discharge and thereafter at 1, 3, 6, 9 and 12 months. At 3 and 12 months after discharge an echocardiogram and laboratory studies were to be performed in all patients and an exercise stress test in patients able to exercise. Non-programmed visits could be dictated by medical reasons other than control of blood pressure. RESULTS The baseline characteristics of patients randomized to each group with available blood pressure measurements in follow-up are presented in Table I. A past history of hypertension 225
4 Rev Port Cardiol Vol. 24 Fevereiro 05/ February 05 Table 1 Baseline characteristics of randomized patients with available follow-up blood pressure evaluation. SIFUP COD n=89 N=68 p Sex Male n (%) 63 (70.8) 49 (72.1) 0.86 Age mean ( SD) 60.8 (12.7) 60.8 (11.2) 0.96 Previous risk factors Hypertension n (%) 58 (61.1) 37 (54.7) 0.14 Diabetes n (%) 20 (22.7) 21 (30.9) 0.25 Hypercholesterolemia n (%) 52 (59.1) 37 (54.4) 0.56 Current smokingn (%) 30 (34.1) 27 (40.3) 0.29 Previous cardiovascular events* n (%) 29 (33.0) 17 (25.0) 0.16 Discharge diagnosis Unstable angina n (%) 18 (20.2) 11 (16.2) Non-Q wave MI n (%) 38 (42.7) 26 (38.2) Q-wave MI n (%) 33 (37.0) 31 (45.6) 0.54 * Previous hospital admission for acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft or stroke. MI: Myocardial infarction. was frequent in both groups and the proportion of hypertensive patients was higher in the SI- FUP group. No significant differences were found in baseline characteristics between groups. The proportion of patients with normal blood pressure values was higher in the SIFUP than in the COD group (respectively 57.5% and 48.5%, p=ns). Adequate blood pressure control was achieved in a minority of hypertensive patients. In SIFUP 26 (44.8%) patients with past history of hypertension had controlled blood pressure and in the COD group only 8 (24.2%) patients achieved the target blood pressure (p=0.05). No differences were found between the SI- FUP and COD groups in systolic, mean or diastolic blood pressure in the overall study po- pulation. However, considering only hypertensive patients, systolic and mean blood pressure were significantly higher in the COD group (Fig. 1). Although not statistically significant, diastolic blood pressure was higher in the COD group as well. Pulse pressure was higher in patients randomized to the COD group (62.7mmHg) than in patients following the SIFUP (56.7 mmhg, p=0.06). Adjusting for diastolic BP, pulse pressure was 6.0 mmhg lower in the SIFUP group in all patients (p=0.06) and 7.8 mmhg in hypertensive patients (p=0.08). A higher number of anti-hypertensive agents were used in the SIFUP (mean 2.2 drugs per patient versus 1.8 in the COD group, p=0.004). DISCUSSION This study shows that different methods of follow-up have different results in blood pressure control. Use of structured intensive programs could increase the number of controlled patients, in comparison with appointments at the cardiologist s discretion. An additional effort was made to obtain unbiased and accurate estimates of blood pressure levels in each patient. Blood pressure measurements were performed by an experienced observer, not aware of randomization status. Two measurements of blood pressure were taken in each clinical evaluation to obtain a more reliable estimate of patients usual values. However, a significant number of randomized patients could not have a blinded evaluation, because some patients were unable to come to the hospital for an extra examination outside of their programmed appointments, for personal or employment-related reasons. Other patients moved away from their previous address and so contact was lost. This limitation 226 Fig. 1 Systolic, mean and diastolic blood pressure of hypertensive subjects randomized to SIFUP and COD.
5 PEDRO S. MATEUS, et al Rev Port Cardiol 2005; 24: could lead, to some degree, to a biased result. However, the response rate was similar in the two groups and no differences were found in baseline characteristics between patients who were evaluated and those who were not. The difference found between the two groups was partially due to the higher number of anti-hypertensive agents that patients in the SIFUP reported using. Nevertheless, it is likely that a structured program with a higher number of follow-up visits would improved compliance with anti-hypertensive therapy and increased patients motivation for life-style modification, thus leading to better results from therapy. A recent trial comparing follow-up of hypertensive patients either every three months or every six months found no differences between the two time intervals (7). However, this trial was conducted in a primary care setting and in stabilized hypertensive patients. Our study suggests that in a high cardiovascular risk population admitted for acute coronary syndrome, implementation of a SIFUP could improve longterm blood pressure control. Control of blood pressure was poor in both groups. We should consider, however, that these patients probably had more severe hypertension and were more frequently diabetic than the general population or unselected hypertensive patients. The reduction of blood pressure was more noticeable in systolic blood pressure than in diastolic blood pressure. This finding is consistent with other reports of population-based studies, reflecting easier and more frequent control of diastolic blood pressure. Systolic blood pressure was lowered by about 10 mmhg in the hypertensive patients in the SIFUP, compared to the COD group. This additional reduction in blood pressures levels is clinically significant and could lead to a better long-term prognosis, by reducing recurrent coronary or cerebrovascular events. As patients in SIFUP had more visits to the hospital and used more anti-hypertensive drugs, a cost-effectiveness analysis should be performed to confirm the advantages of such a program. ACKNOWLEDGEMENT This study was supported by a grant from Comissão de Fomento da Investigação em Cuidados de Saúde, Ministry of Health, P.I. no. 16/01. REFERENCES 1. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, Godwin J, Qizilbash N, Taylor JO, Hennekens CH. Blood Pressure, stroke and coronary heart disease. Part 2, Short-term reductions in blood pressure: over-view of randomised drug trials in their epidemiological context. Lancet 1990;335: Dalhöf B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-hypertension). Lancet 1991;338: Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. JAMA 2003;289(19): Charpentier G, Genes N, Vaur L, Amar J, Clerson P, Cambou JP, Gueret P; ESPOIR Diabetes Study Investigators. Control of diabetes and cardiovascular risk factors in patients with type 2 diabetes: a nationwide French survey. Diabetes Metab. 2003;29(2 Pt 1): Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, Joffres MR, Poulter N, Primatesta P, Stegmayr B, Thamm M. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension. 2004;43(1): Guidelines Committee European Society of Hypertension European Society of Cardiology guidelines for the management of arterial hypertension. Journal of Hypertension 2003,21: Birtwhistle RV, Godwin MS, Delva MD, Casson RI, Lam M, MacDonald S et al. Randomised equivalence trial comparing three month and six month follow-up of patients with hypertension by family practitioners. BMJ 2004;328 (7433): CONCLUSIONS The proportion of patients with controlled Pedidos de separatas para: BP was consistently higher in the SIFUP. Pulse Address for reprints: pressure was also reduced in SIFUP patients. PEDRO S. MATEUS The SIFUP has shown to be effective in lowering blood pressure in hypertensive coronary Centro Hospitalar de Vila Nova de Gaia Serviço de Cardiologia patients and the observed reduction in blood VILA NOVA DE GAIA pressure appears to be clinically significant. PORTUGAL 227