Published online before print January 19, 2009, doi: 10.1161/CIRCULATIONAHA.108.812172
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(Circulation. 2009;119:515-523.)
© 2009 American Heart Association, Inc.
Heart Failure |
Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003
A Population Study of 5.1 Million People
From BHF Glasgow Cardiovascular Research Centre (P.S.J., J.J.V.M.) and Department of Public Health (P.S.J., K.M., J.D.L.), Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom; Centre of Academic Primary Care (C.R.S.), University of Aberdeen, Aberdeen, United Kingdom; Baker Heart Research Institute (S.S.), Melbourne, Australia; Information Services Division (A.R., J.W.T.C.), Edinburgh, United Kingdom; and Department of Public Health (S.C.), University of Liverpool, Liverpool, United Kingdom.
Correspondence to Professor John J.V. McMurray, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, United Kingdom. E-mail j.mcmurray{at}bio.gla.ac.uk
Received August 1, 2008; accepted November 21, 2008.
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Abstract |
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Background— We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF.
Methods and Results— All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, β-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend).
Conclusions— After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.
Key Words: heart failure • epidemiology • survival • drugs
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Introduction |
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Heart failure (HF) reduces the quality and quantity of life for afflicted individuals and exerts a substantial drain on healthcare resources.1 Thus, any change in the epidemiology of the disease has important implications at the personal and societal level. Until recently, it was commonly stated that we were in the midst of an epidemic of HF.2 Toward the end of the last century, however, reports emerged from a number of countries to suggest that the incidence of first hospitalization for HF may have peaked or even started to decline, although there was some doubt expressed about this.3–7 Subsequent reports suggested that the poor survival of patients hospitalized with HF (as well as those in the community3,4) might also be improving.5,8–10 Whether that increase has been sustained is unknown.
Clinical Perspective p 523
It was suggested that some of the improvements reported were related to improvements in treatment of HF, particularly the use of angiotensin-converting enzyme (ACE) inhibitors, during the time periods investigated.11 Since then, additional treatments, notably spironolactone12 and β-blockers,13 have been shown to further improve survival and reduce hospitalizations for HF in patients with left ventricular systolic dysfunction. The association between the use of these drugs and clinical outcomes has not been explored at a population level. We have therefore determined whether the improvements in hospitalization rates and survival we reported for an entire country in the period 1986 to 1995 have been sustained to 2004, using a national administrative database that allows record linkage at the individual patient level. In addition, we examined the prescribing rates of evidence-based therapies (ACE inhibitors, β-blockers, and spironolactone) for individuals with HF in the same country during the same period using another health service administrative database of prescribing practices in primary care.
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Methods |
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Data Sources
Using previously described methods,14 we examined all discharges (including patients who died as inpatients and those discharged alive) since 1981 from National Health Service hospitals, which provide free care and account for virtually all hospitalizations in Scotland. Discharge diagnoses, demographics, prior admissions, postal code (which allows evaluation of socioeconomic status), and length of stay are recorded. Diagnosis at discharge is coded with the International Classification of Diseases (ICD) system (ICD 9th revision until April 1996, ICD 10th revision thereafter). Each patient is given a principal diagnosis and up to 5 secondary diagnoses. The accuracy of cardiovascular diagnoses is >91% overall,15 and an ICD code for HF in a primary diagnostic position was as high as 94% accurate in 1 study.16 Records are linked by probability matching (with an accuracy of
98%), which permits analysis of data at the level of the individual patient and the episode of care. These data are linked to the Registrar General’s Death Certificate Data with an accuracy of 98%, so that if a patient dies, that outcome is recorded. For the present study, we identified all individuals with a first discharge from hospitals with a principal diagnosis of HF (ICD 9th revision code 425.4, 425.5, 425.9, 428.0, 428.1, 428.9, or 402; ICD 10th revision code I50, I42.0, I42.6, I42.7, or I42.9). A first discharge was defined as one with an HF code in a primary diagnostic position, with no previous hospitalization for HF (in any diagnostic position) since 1981, ie, a minimum of 5 years previously. To ensure that the look back to 1981 did not result in an artifactual decline in HF hospitalizations due to an increasing look back, we also examined the proportion of cases that would be added if a 5-year look back were applied to all years. This altered 0.7% of the data over the entire period through the double counting of some individuals. We therefore analyzed our data using the look back to 1981. Left ventricular ejection fraction and drug therapy were not recorded. A comorbid diagnosis was one that was coded as a secondary diagnosis during the index hospitalization or as the principal diagnosis during a prior hospitalization within 5 years of the index hospitalization. The following comorbidities were included: atrial fibrillation, any cancer, cerebrovascular disease, any coronary heart disease, diabetes mellitus, hypertension, peripheral arterial disease, renal failure, and respiratory disease.14 We used post-code sectors to allocate Carstairs deprivation quintiles on the basis of 4 variables from the 1991 census, namely, male unemployment, overcrowding, social class, and car ownership.17
In Scotland, all citizens have free access to primary care services and, among the elderly, free prescriptions through the National Health Service. All prescriptions are provided via primary care, with the exception of a short supply of drugs provided by hospitals immediately after patient discharge. Subsequent repeat prescriptions are provided through primary care, as are those for treatments recommended during hospital clinic visits. To examine prescription of HF therapy, we used another National Health Service database in which extensive information is collected from a representative sample of general practices in Scotland, as described elsewhere.18 In 1997, 37 practices and 208 234 patients were covered, extending to 58 practices and 348 820 patients by 2003 (representing 7% of the Scottish population). The completeness and accuracy of coding are audited continuously by the Information and Statistics Division of the National Health Service in Scotland and are 91%.18 These patients are representative of the whole Scottish population in terms of age, sex, socioeconomic status, and rural-urban mix. We identified all patients who had a consultation that generated an HF-related Read code (G58., G580., G5800, G5801–3, G581., G5810, G582., G58z.) from April 1997 to March 2003. Prescription data for these individuals were obtained to describe which HF medications (ACE inhibitors, β-blockers, or spironolactone) these patients took on a regular basis. Newly started medications (that is, those for which a second prescription had not been issued) were not analyzed. The prescription rates reported may therefore slightly underestimate the true rate of use of the drugs concerned.
Statistical Analysis
Survival times were calculated from the first admission with HF to death due to any cause at 30 days, 1 year, or 5 years or censoring at December 31, 2004. Censoring occurred at December 31, 2004, because complete national follow-up death data were only available to that point at the time of data extraction. Hospital discharge rates were age standardized by direct standardization to the 2001 Scottish census population. Crude case-fatality rates were calculated for follow-up periods at 30 days, 1 year, and 5 years by the life-table method. Kaplan-Meier analyses were used to determine median survival. Median survival could only be calculated if 50% of individuals had died. Logistic regression was used to model case fatality at 30 days and Cox proportional hazard models to examine predictors of death within 1 and 5 years. We included all patients hospitalized with HF between 1986 and 2003 for death at 1 year and between 1986 and 1998 for death at 5 years. The assumption of proportional hazards was met for these models. Models included age, socioeconomic deprivation, year of hospitalization, and comorbid diagnoses. An interaction was found between sex and year of admission (P<0.0001), and thus, sex-specific analyses are presented.
A joinpoint regression was fitted to provide the estimated annual percentage change and to detect points of significant changes in the trends (Joinpoint software, version 3.0). The Bayesian information criterion was used to select the best-fitting model.19 A maximum of 3 joinpoints were allowed for estimations. For each estimate, the 95% CIs were also calculated.
Prescribing rates were calculated for men and women separately and standardized by direct standardization with the 2001 population with HF for whom prescribing data were available. All analyses were undertaken with Stata 9 (StataCorp LP, College Station, Tex).
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
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Results |
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A total of 116 556 individual patients (55 173 men [47.3%] and 61 383 women [52.7%]) were discharged from the hospital for the first time with HF between 1986 and 2003. The mean age at first discharge increased progressively from 70.7 years (95% CI 70.3 to 71.2 years) in 1986 to 72.4 years (95% CI 72.0 to 72.9 years) in 2003 (P for trend <0.0001) in men and from 76.0 years (95% CI 75.7 to 76.4 years) in 1986 to 77.3 years (95% CI 76.8 to 77.8 years) in 2003 (P for trend <0.0001) in women.
The age-standardized rate of first hospitalization with HF (per 100 000 population) in men increased from 124 (95% CI 119 to 129) in 1986 to 162 (95% CI 157 to 168) in 1994, an annual percentage change of 3.22% (95% CI 1.96% to 4.50%, P<0.0001; Figure 1). The trend reversed in 1994 (95% CI 1992 to 1995), and the rate fell to 105 (95% CI 101 to 109) in 2003, an annual percentage change of –4.10% (95% CI –5.10% to –3.10%, P<0.0001). A similar pattern was seen in women (Figure 1). The rate increased from 128 per 100 000 (95% CI 123 to 132) in 1986 to 160 (95% CI 155 to 165) in 1993, an annual percentage change of 3.02% (95% CI 2.22% to 3.84%, P<0.0001). The trend again reversed in 1994 (95% CI 1993 to 1995), with the rate falling to 101 (95% CI 97 to 105) in 2003, an annual percentage change of –4.55% (95% CI –5.20% to –3.90%, P<0.0001).
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In contrast to first admissions, repeat admission rates increased during the period of study. The proportion of men surviving to discharge who were readmitted at 1 year was 21.0% (95% CI 19.4% to 22.5%) in 1986 and 31.0% (95% CI 29.2% to 32.7%) in 2003. The respective proportions in women were 19.8% (18.4% to 21.2%) and 27.7% (26.0% to 29.4%).
Age had a large effect on crude case fatality (Table 1). Although crude case fatality was apparently higher among women in unadjusted analyses, adjustment for age removed this difference and lowered case fatality in women to that of men (Table 2
). The prevalence of comorbidities increased over the study period with the exception of myocardial infarction, which fell over the study period (see online Data Supplement). Crude case fatality was particularly high in those with a history of prior or comorbid diagnosis of cancer, renal failure, or respiratory disease and was also higher in those with cardiovascular disease (cerebrovascular, coronary, or peripheral arterial disease; Table 1). Socioeconomic deprivation had minimal effects on crude case-fatality rates at 30 days, 1 year, and 5 years.
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Median survival after a first hospitalization with HF increased in men from 1.33 years (95% CI 1.17 to 1.50 years) in 1986 to 2.34 years (95% CI 2.15 to 2.56 years) in 2002 (P<0.0001; Figure 2). For the 2003 cohort of men, 50% of the cohort had not died by the end of follow-up. In women, median survival increased from 1.32 years (95% CI 1.19 to 1.44 years) in 1986 to 1.79 years (95% CI 1.50 to 1.98 years) in 2003 (P<0.0001; Figure 2).
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Similarly, age at death increased for both men and women. In men, it increased from 74.0 years (95% CI 73.6 to 74.4 years) in 1986 to 77.3 years (95% CI 76.7 to 77.9 years) in 2003 (P for trend <0.0001). In women, age at death increased from 79.1 years (95% CI 78.7 to 79.4 years) in 1986 to 81.4 years (95% CI 80.9 to 81.9 years) in 2003 (P for trend <0.0001). After adjustment for other factors in a multivariable analysis, increasing age had the greatest impact on case fatality at 30 days, 1 year, and 5 years in both men and women (Table 3).
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Median survival improved more in men than in women (Figure 2), as did the adjusted risk of death at 30 days and 1 and 5 years (Figure 3). After adjustment for age, deprivation, and comorbidity, 30-day survival improved steadily from 1986 to 2003 in both men and women. The odds of death at 30 days in 2003 compared with 1986 were 0.52 (95% CI 0.45 to 0.6) in men and 0.77 (95% CI 0.67 to 0.88) in women. One-year survival improved similarly. The hazard of death at 1 year in 2003 compared with 1986 was 0.62 (95% CI 0.57 to 0.68) in men and 0.77 (95% CI 0.71 to 0.84) in women. The hazard of death at 5 years after hospitalization with HF in 1999 compared with 1986 improved in men (0.71, 95% CI 0.67 to 0.75) and women (0.78, 95% CI 0.74 to 0.83).
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The decline in overall mortality reflected a fall in cardiovascular mortality, with a reduction in all modes of cardiovascular death. In contrast, the proportion of deaths due to noncardiovascular causes rose.
The age-standardized prescribing rates (per 100 patients with HF) for ACE inhibitors in men increased from 32 (95% CI 28 to 36) in 1996/1997 to 54 (95% CI 51 to 58) in 2002/2003 (P<0.0001; Figure 4), and in women, they increased from 28 (95% CI 24 to 31) in 1996/1997 to 53 (95% CI 49 to 56) in 2002/2003 (P<0.0001; Figure 4). The rate of use of β-blockers (per 100 population) also increased in men from 11 (95% CI 9 to 14) to 35 (95% CI 33 to 38; P<0.0001), whereas in women, the rate increased from 11 (95% CI 9 to 14) to 37 (95% CI 35 to 40; Figure 4) between 1996 and 2003. Spironolactone prescribing rates also increased in men from 1 (95% CI 0.4 to 2) to 9 (95% CI 8 to 11; P<0.0001) and in women from 1 (95% CI 0.3 to 2) to 11 (95% CI 10 to 13; P<0.0001) between 1996 and 2003.
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Discussion |
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The previously rising age-adjusted rates of first hospitalization for HF are clearly declining. There have been corresponding and sustained improvements in survival at 30 days, 1 year, and 5 years. Age at discharge and age at death have also both increased. Age-adjusted, population-based rates of prescribing evidence-based therapies (ACE inhibitors, β-blockers, and spironolactone) to patients with HF have also increased in parallel with these findings.
Trends in Incidence of First Hospitalization for HF
We described incident first hospitalizations for individual patients. The present new data confirm that at a country level, the decline in HF hospitalization rates initially reported in the early 1990s6,14 has been sustained since. After our original description of a plateau and decline in HF hospitalization rates in Scotland in the period 1990 to 1996,14 there was some concern that this observation might be premature or unrepresentative of other countries.20 Since then, similar population trends have been identified over more recent time periods in the Netherlands (1980 to 1999),7 Sweden (1988 to 2000),5 and Leicestershire, England (1993 to 2001).9 We have now shown that the decline in HF hospitalizations has continued in the new century and at a time when additional disease-modifying therapies have been introduced into clinical practice (see below).
A number of factors could have accounted for the steep decline in incident hospitalization for HF, including improved prevention of HF. This may have occurred through better detection and management of hypertension. It is estimated that mean blood pressure in the population decreased by 9% in Scotland between 1974 and 199421 (with similar falls seen in other parts of the United Kingdom22), whereas use of antihypertensive therapy increased.21 Data from the Scottish center of the World Health Organization MONICA (MONItoring of trends and determinants in CArdiovascular disease) studies confirmed these falls in addition to reductions in smoking prevalence of 11% and in population serum cholesterol by 0.5 mmol/L between 1976 and 1996.23 Both the primary and secondary prevention of coronary heart disease improved throughout the study period. For example, the use of statins doubled in 1 study in Scotland after publication of studies on the efficacy of statins.24 Further increases were reported throughout the mid 1990s to 2002, whereas at the same time, increases in the use of other therapies were seen, so that by 2002 in Scotland, 36% of those with coronary disease received an ACE inhibitor, 50% a β-blocker, and 75% an antiplatelet agent.25 By 2002 in Scotland, nearly 90% of those with coronary disease were taking at least 1 such agent.25 Furthermore, the improved treatment of HF after its development, including the introduction of multidisciplinary management programs, may have also contributed to this fall.26 The lack of a clear decline in the incidence of HF in community studies suggests the latter may be more important, although there may also have been changes in the threshold for hospital admission during the period of study.3,27 Interestingly, the proportions of both men and women readmitted after an incident hospitalization increased during the study, consistent with improved survival over this period (see below).
Trends in Survival
We found that the decline in short-term (30-day) and medium-term (1-year) case fatality after HF hospitalization reported in Scotland between 1986 and 199514 continued through 2004. The rate of decline in the more recent study period was similar to that in the earlier period and remained more striking in men than in women. As a consequence, the relative fall in short- and medium-term case-fatality rates over the entire period 1986 to 2004 was on the order of 40% to 50% in men and 20% to 25% in women. Few other studies have reported time trends in population-based survival after HF hospitalization. A study from Sweden (1988 to 2000)5 and a study from a county in England (1993 to 2001)9 also showed improvements in 30-day and 1-year survival, whereas a study from the province of Ontario in Canada (1992 to 2000)28 showed an improvement in 1-year but not 30-day outcomes. Although the treatment of acute HF has not altered greatly during the study period, it is possible that the early introduction of ACE inhibitors, β-blockers, and spironolactone to individuals hospitalized with HF may have contributed to these trends. It is noteworthy that in meta-analysis of the use of ACE inhibitors in HF, beneficial effects were seen within 90 days.29 The effects of β-blockers in HF are also rapid, occurring by 14 to 21 days.30 Similarly, the impact of early, postdischarge home visits by specialist nurses is also seen quickly.26 We were able to extend these observations and determine trends in long-term case fatality, ie, at 5 years. These data were, by definition, only available in patients hospitalized up to 1999 (as opposed to 2003 for the 30-day and 1-year analyses). There were, however, linear, continuous decreases in long-term case fatality on the order of 29% for men and 22% in women over this period, which indicates sustained improvements in survival that are of clinical and public health significance. These improvements were reflected in a steady increase in age at death in patients hospitalized with HF. Absolute survival after a first hospitalization for HF, however, remained poor in both sexes, and in 2002, half of the men were dead at 2.3 years after first hospitalization, and half of the women were dead at 1.7 years.
As with the reductions in rates of hospitalization, it is difficult to be certain of the reasons for the observed improvements in survival. An effect of the enhanced use of disease-modifying therapy is, however, supported by the increased prescription of ACE inhibitors, β-blockers, and spironolactone to patients with HF that we documented at the population level (see below). Interestingly, however, the decline in case fatality for HF was apparent before the decline in incident HF hospitalizations. Before 1994, the rise in incident admissions and the fall in case fatality for HF might have suggested an effect of reduced hospital admission thresholds, such that an increased proportion of milder cases were being admitted to hospital. However, the decline in admission rates after 1994, without a noticeable change in the downward trend in case fatality, suggests that any changes in hospital admission thresholds are not likely to be relevant.
The greater improvement in survival in men than in women may reflect the higher proportion of female patients with HF and preserved ejection fraction and the lack of proven disease-modifying therapy for this type of HF. One other study has shown less improvement in survival in HF with preserved compared with reduced ejection fraction.31
Trends in Prescribing Practice
During the period covered by the study, prescribing rates for ACE inhibitors, β-blockers, and spironolactone were similar in men and women and increased similarly. This finding is consistent with other studies from Europe, Canada, and the United States.4,7,32–35 Even if it is assumed that 30% to 40% of patients with HF have a preserved ejection fraction, prescribing rates for β-blockers and spironolactone are probably still suboptimal.34 If better use of disease-modifying therapy does account for much of the improvement in outcomes we have reported, the potential benefits of further increases in uptake of β-blockers and aldosterone antagonists, as well as angiotensin receptor blockers, devices (cardiac resynchronization therapy and implantable cardioverter defibrillators), and multidisciplinary disease management programs, are obvious.36
Study Limitations
In the present study, we only examined discharges from the hospital and did not examine new diagnoses of HF in the community. Furthermore, we were not able to differentiate between HF with preserved versus reduced left ventricular function, although recent reports would suggest that the prognosis is similar in both forms of HF.31 Finally, prescribing data for each hospitalized individual were not available.
Conclusions
Population-based, age-adjusted rates of first hospitalization for HF continue to decrease in both men and women. Adjusted survival also continues to increase, with year-on-year improvements for almost 2 decades. These improvements have occurred in parallel with increased population-based prescription of disease-modifying therapies for HF. However, absolute survival remains poor, and rates of prescription of evidence-based therapies are still suboptimal in patients with HF.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.108.812172/DC1.
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