Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis

Abstract

Background: Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines.

Methods: We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series.

Findings: Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10,900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0·0001). Starting in March, 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05-0·16, p<0·0001). By March, 2013, 35 more cases per month were reported than would have been expected had the previous trend continued. This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk.

Interpretation: Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines.

Funding: Heart Research UK, Simplyhealth, and US National Institutes of Health.

Figure 1

The total number of prescriptions for antibiotic prophylaxis (AP) dispensed each month: (a) Division by prescription (single 3g oral amoxicillin, BLUE; single 600mg oral clindamycin, PURPLE) (b) Division by prescriber (dentists, MAGENTA; general medical practitioners, BLUE; nurse practitioners, RED; hospitals, BLACK). The grey bar indicates March 2008, the month in which cessation of AP for infective endocarditis (IE) was recommended by NICE.

Figure 2

The number of infective endocarditis (IE) cases (superspells) recorded each month (solid BLACK line) and associated in-patient mortality (solid RED line). The data are corrected for change in the size of the English population. The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis (AP) for IE was recommended by NICE. The trend lines for IE incidence (dashed BLACK lines) and associated in-patient mortality (dashed RED lines) before and after introduction of the NICE guidelines are also shown. NOTE: with the IE cases March 2012 outlier value removed the change in the IE incidence trend line remains statistically significant (change in level = −0·28, CI −2·27–1·7, p=0·78; change in slope = 0·09, CI 0·04–0·14, p<0·001)

Figure 3

The number of infective endocarditis (IE) cases recorded each month affecting ‘lower-risk’ (solid BLACK line) and ‘high-risk’ (solid RED line) individuals. The data are corrected for change in the size of the total English population (not for change in the size of population at ‘high-risk’ or ‘lower-risk’ of IE). The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis (AP) for IE was recommended by NICE. The trend lines for ‘lower-risk’ (dashed BLACK lines) and ‘high-risk’ (dashed RED lines) cases before and after introduction of the NICE guidelines are also shown.

Figure 4

The number of IE cases recorded each month in individuals at ‘high-risk’ of developing IE, according to category of ‘high-risk’ status (previous IE, previous prosthetic replacement of heart valve, previous repair of heart valve, pre-existing congenital heart disease repaired with prosthetic material [only within the previous 6 months], pre-existing congenital heart disease with surgical shunt or conduit, pre-existing unrepaired congenital cyanotic heart condition, pre-existing artificial heart or ventricular assist device). The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis for IE was recommended by NICE.

Figure 5

The number of population-corrected IE cases per 10 million population per month (solid BLACK line). The vertical dashed black line indicates March 2008, the month in which cessation of antibiotic prophylaxis for IE was recommended by NICE. The red lines show the result of change-point analysis, indicating that the change occurred in June 2008.