How well are we implementing evidence-based care?

To address the question of how well we are implementing evidence-based care, I will review data from existing European registries using the European Heart Failure Survey (EHFS) I and EHFS II, as well as national registries. My review will focus on the rates of uptake of two accepted measures of performance: (1) measurement of LV function in all patients, and (2) treatment with ACE inhibitor and beta-blocker in patients with left ventricular systolic dysfunction (LVD). EHFS I was a very large survey of data collected in 2000–2001 from 24 European countries for over 11 000 patients referred to hospital with suspected or confirmed heart failure.1,2 Individual hospital data for rates of echocardiography showed huge heterogeneity, with some centers performing echocardiography in only 20–30% of patients. The average rate of echocardiography was 58%. In the prescription of recommended medications, only 62% of patients received an ACE inhibitor and only 37% a beta-blocker (a rate similar to that for cardiac glycosides). Twenty percent of patients were on spironolactone and, not surprisingly because of the date of the survey, a limited proportion were on an angiotensin receptor blocker. A subanalysis of EHFS I based on ejection fraction (EF) revealed that patients with an EF <40% received higher rates of recommended prescriptions than the overall population, but again these rates were far from optimal: 80% of patients were on ACE inhibitors and only 49% on beta-blockers. As shown in Figure 1, the mean dose for ACE inhibitors was below the target dose. For beta-blockers, the rate of underdosage was worse than for ACE inhibitors. Figure 2 shows that only a minority of patients were receiving even 50% of the target beta-blocker dose, while a number were receiving a beta-blocker not recommended for heart failure; this may suggest that a proportion of these patients were being treated for their underlying disease rather than for heart failure. Similar to the variability in rates of use of echocardiography between hospitals, there was a wide range in the use of ACE inhibitor therapy, with some centers treating <40% of patients with an ACE inhibitor. Heterogeneity in the use of beta-blocker therapy between hospitals was even greater than for ACE inhibitors, and some hospitals prescribed beta-blockers in less than 20% of patients. The three main lessons from EHFS I are that, at the time of the survey, there existed: (1) an underuse of medications, (2) an underdosage of these medications, and (3) a huge heterogeneity across participating centers. These shortcomings were not entirely the responsibility of the healthcare professionals involved. Modeling analysis in EHFS I identified a number of factors associated with low prescription of beta-blockers. Among these was the presence of respiratory disease, which was associated with a two-thirds reduction in the likelihood of beta-blocker prescription. Specialty at admission also influenced beta-blocker use. A cardiology specialty was associated with a greater likelihood of beta-blocker prescription compared to a general or internal medicine specialty. Finally, age >70 years and female gender were independent predictors for not receiving a beta-blocker. Has the situation improved since the time of EHFS I? EHFS II was performed in 2004/2005 and included a database of 3500 patients.3 The criteria for inclusion differed slightly compared to EHFS I, but a comparison of the outcomes provides a valuable insight. Comparison of the rates of EF measurements showed an improvement, from 58% in EHFS I to 80% in EHFS II. The use of recommended medications showed a slight increase at the time of admission and a remarkable increase prior to discharge, suggesting that physicians may now be taking account of the European Society of Cardiology (ESC) guidelines (Figure 3). Data from a French registry of national hospitals in 2002 showed a very similar situation to the EHFS I data, as only 20% of patients were on beta-blockers at discharge.4 However, analysis of survey data between 1997 and 2003 indicates a temporal trend to improved prescription of both ACE inhibitors and beta-blockers in France (Figure 4). Data from Italian registries provide a similar message. While the rates of prescriptions of ACE inhibitors remained stable between 1995 and 2005, rates of prescriptions of beta-blockers, aldosterone blockers, and angiotensin receptor blockers improved over this period.5 At the same time, prescriptions of purely symptomatic drugs, such as digitalis, declined, from 70% in 1995 to 27% 10 years later. These data together suggest that there has been an improvement across Europe in the rate of prescription of recommended medications in patients referred to hospital for heart failure. It might be argued that hospitalized patients are selected patients who are treated by physicians better skilled at prescription. In order to investigate changes in outpatient therapy, the French IMPACT RECO study surveyed the prescriptions of 1917 outpatients treated by 515 cardiologists in 2005, before publication of the updated ESC guidelines on heart failure.6,7 These cardiologists then underwent an educational program including district meetings at which the changes to the guidelines were explained and discussed. The second wave of IMPACT RECO included 1974 outpatients treated by 537 cardiologists. Comparison of the rates of prescriptions in IMPACT RECO I and II identified a stable rate of ACE inhibitor prescription (71% vs 68%) and spironolactone prescription (35% vs 35%), but an increase in prescription of beta-blockers (65% vs 70%) and angiotensin receptor blockers (21% vs 30%) (Figure 5). Rates of prescription of purely symptomatic treatments changed little. Looking specifically at the rates of prescription of recommended combinations, there was again an increase between the two phases. Use of ACE inhibitor or angiotensin receptor blocker plus beta-blocker increased from 60% to 66% and use of ACE inhibitor or angiotensin receptor blocker plus beta-blocker plus diuretic increased from 50% to 57% (Figure 6). Looking at doses, there was an improvement in the proportions of patients achieving the target dose between IMPACT RECO I and II, from 49% to 57% for ACE inhibitors and from 18% to 24% for beta-blockers. Similar improvements were seen in patients receiving at least 50% of the target dose (Figure 7). Cardiologists were questioned during IMPACT RECO II for their reasons for not prescribing an ACE inhibitor or angiotensin receptor blocker. Cough was the most common reason for not prescribing an ACE inhibitor (60% of cases), while hypotension was mentioned infrequently (10%). Notably, 19% of cardiologists offered no answer. Reasons for not prescribing an angiotensin receptor blocker were slightly different. The main reason for non-prescription was “not indicated”, which is not surprising given the mild-moderate heart failure population and that most patients were receiving an ACE inhibitor. Again, 25% of cardiologists offered no reason for not prescribing an angiotensin receptor blocker. The most common reasons for not reaching the target dose of ACE inhibitor or angiotensin receptor blocker were hypotension and renal failure, which together applied to approximately three quarters of patients. These represent valid, patient-related reasons. For beta-blockers, asthma or COPD were the most common reasons for non-prescription (38%), followed by ‘side effects’ in another 30%. Again, 12% of cardiologists provided no reason for not prescribing beta-blockade in these patients. Hypotension (38%) was the most common explanation for not reaching the target beta-blocker dose. These outcomes of the IMPACT RECO study show that there is an improvement in the prescription of recommended medications in the outpatient population following an educational program. The elderly population is growing in importance and there is evidence that these patients are not being treated as they should be. There are currently no guidelines and no trials that address this population. A recent analysis of EHFS I investigated the treatment of patients aged 80 years or more, and found that only a minority (38%) had received an assessment of left ventricular function, compared to 65% in the remaining population.8 Even worse was the under prescription of recommended drugs in the elderly, with rates of 50% for an ACE inhibitor, 24% for a beta-blocker, and 15% for spironolactone, which compare with rates of 66%, 42%, and 23%, respectively, in younger patients. By contrast, a higher proportion of elderly than younger patients were treated with purely symptomatic medications: loop diuretics (86% vs 78%), nitrates (49% vs 46%), and digoxin (43% vs 30%). Looking at the dosages received, only a minority of the elderly were receiving >50% of the target does of ACE inhibitor (14%) or beta-blocker (5%), which compares to rates of 26% and 11%, respectively, in younger patients. There are a number of potential explanations for why elderly patients may be treated differently to younger patients. Among these is the type of medical service that patients receive, as many elderly patients are hospitalized in general medicine or long-term institutions. Gender difference might also play a role, as women represent a higher proportion of the elderly. Other potential factors include the higher prevalence of heart failure with preserved systolic function, higher prevalences of contraindications, side-effects, and comorbidities, and physician reluctance. Additional analyses of prescription rates in the elderly has suggested, however, that among these potential explanations, there are no gender differences in prescription rates and little impact from the higher prevalence of preserved systolic function. Modeling analysis identifies that comorbidities such as renal dysfunction, dementia/confusion, infection, cancer, and respiratory disease as associated with a lower likelihood of ACE inhibitor or beta-blocker prescription, while age itself is an independent predictor of non-prescription8 (Figure 8). This suggests that, besides the presence of comorbidities and side effects, physicians display a reluctance to provide the recommended medications to the elderly patient. Does a lack of guidelines explain the suboptimal use of medications in heart failure? The evidence rather suggests the contrary - that there may be too many guidelines in chronic heart failure, which include those from the European Society of Cardiology, American College of Cardiology / American Heart Association, Heart Failure Society of America, National Institute for Clinical Excellence, and Scottish Intercollegiate Guidelines Network, and that prescribers are overwhelmed with information. Some of these documents, in particular the North American guidelines, are lengthy documents containing large numbers of pages. To improve the implementation of guidelines, they should be concise, consistent, and regularly updated in order to provide a good service to professionals. A recent survey in 7 European countries interviewed cardiologists to measure their awareness of the ESC guidelines and to identify barriers to adopting the recommendations (Figure 9).9 Overall, awareness of the ESC guidelines was good among cardiologists (84%, when prompted). The main barrier to implementing the guidelines' recommendations was identified to be patient compliance (82%), followed by the complexity of the guidelines (46%) and a lack of time to read them (46%). The most relevant supports to adhering to the guidelines were identified to be a compact, short, summary format (mentioned by 73% of cardiologists) and email updates (55%). The ESC has made excellent efforts to meet these needs by producing its Pocket Guidelines, which are easy to read and user friendly. To further improve guidelines implementation, there is a need for all scientific societies to cooperate together to produce joint guidelines and a requirement to integrate educational programs within each specialty and between specialties. The pharmaceutical industry has a role to play in this process as a vector for information. Despite the limitations of current guidelines, they represent a valuable tool to improve patient care. This is exemplified by the MAHLER survey, which was conducted two years ago on 1500 patients across six European countries, and which showed a close relationship between adherence to guidelines and reduction in hospitalizations10 (Figure 10). This and other evidence strongly indicates the importance of guidelines in providing a better service to patients.