Increased aortic repair in Germany correlates with reduction of death caused by aortic aneurysms but not aortic dissections

Abstract

Introduction

We asked if there is a significant correlation between the increasing trend in aortic repair (AR) and decreasing aortic aneurysm (AA) and aortic dissection (AD) mortality? Therefore, we retrospectively analyzed all aortic repairs in patients with AA and AD and its correlation with disease-specific death rates and hospitalizations for ruptured AA and AD in Germany.

Methods

We retrieved the number of cases hospitalized for AA and AD as well as the procedures in these cases from the Federal Bureau of Statistics (DRG statistics) and death rates from the national mortality statistic published by the Federal Statistical Office in Germany for the years 2006–2017.

Results

From 2006 to 2017, the total number of hospitalized cases admitted with principal diagnosis of AA increased by 25.8% and that of AD by 56.7%. That of cases with the principal diagnosis of ruptured AA (rAA) remained unchanged (−2.5%) and that with rAD increased by 54.6%. The number of (open and endovascular) procedures in cases hospitalized for AA increased by 39.4% and for AD by 126.4%. The age-adjusted death rates in Germany for AA decreased from 4.0 to 2.9 per 100,000 inhabitants and that for AD increased from 1.0 to 1.4. The decrease in death attributed to AA cases can be described by linear regression as y = −0.0003*y + 6.7076 (p < 0.0001). Accepting this association between increased elective procedures and reduced AA mortality, each/all 1000 procedures save 0.3 lives per 100,000 inhabitants.

Conclusion

Despite increasing numbers of AR for AA and AD, only the mortality rate for all AAs decreased, while we did not observe a decrease in overall mortality of AD in Germany.

Keywords

aortic aneurysm aortic dissection ruptured aortic aneurysm ruptured aortic dissection

Introduction

Common aortopathies include aortic aneurysm (AA) and aortic dissection (AD). Although they may be caused by different etiologies, both are degenerative aortic diseases in the majority of cases and both will lead to aortic rupture as the most severe complication.^1–4 With the aging population, there is a general increase in cases presenting with AA^5–9 and AD.^10–12 On the hand, there is good evidence of a falling incidence of AA disease in Western countries linked to reduced smoking rates¹³ and also evidence from screening studies that aortic diameters are falling on initial screen.¹⁴ In parallel, there is an increasing trend in aortic repair (AR) in patients with AA and AD worldwide.^5,9,10,15 Today, AA is usually treated electively when they reach a size >5 cm to prevent death due to aortic rupture.³ A similar preventive treatment of AD may be performed in patients with chronic AD. The majority of AD patients are treated because of acute symptoms and only a lower part because of critical sizes.¹⁶ In-hospital mortality rates among patients suffering from AA and AD have decreased steadily over time.^9,10,17–20

Several reasons for the decrease in mortality of both diseases have been discussed globally: Establishment of endovascular therapies, risk factor modification, improvement in regional centralization, adequate emergency preparedness, and improvement in surgical training and surgical and postsurgical care.^19,21 It is unclear to what extent each of these reasons has changed mortality in Germany in the last decade. Centralization of services has not happened in Germany as it has elsewhere. Screening for abdominal AA in Germany started in 2018 for the first time and is offered for males only.

We hypothesize that the concept of elective AR in AA patients prevents death due to late AA rupture, and that the same applies for AD. Therefore, we asked if there is a significant correlation between the increasing trend in AR and decreasing AA and AD mortality? To answer this question, we retrieved complete German hospitalization and treatment data sets and analyzed trends in AR for AA and AD as well as death rates for both aortopathies.

Patients and methods

Nationwide hospitalization data

The Diagnosis-Related Groups Statistic (DRG) is an annual complete survey of all hospital cases in Germany that were accounted for by case rates. The microdata can be requested via the RDC starting from the survey year 2005. All hospitals in Germany annually transfer their individual hospitalization data, including one primary diagnosis, up to 89 secondary diagnoses coded by ICD-10 (International Classification of Diseases, 10th edition), and up to 100 medical procedures according to a national classification of operations and procedures to the Institute for the Hospital Renumeration System (InEK). After a plausibility control, the InEK forwards anonymized data to the Federal Bureau of Statistics. Principles of the analysis of this hospitalization file have been published several times previously.^22,23 In brief, we ask the Federal Bureau of Statistics to identify all hospitalizations of the years 2006 through 2017 that have a principal diagnosis of AA (ICD-10: I71.1–I71.9) and AD (ICD-10: I71.00–I71.07) by calendar year, sex, and 5-year age group. These numbers include all thoracic, abdominal, and thoraco-abdominal AA and AD, respectively, and those coded as “unspecified localization.” ICD-10 coding does not reflect the more clinical and anatomic differentiation according to DeBakey in Types I, II, and III or Stanford classes A and B.

In addition, we ask for all treatment procedures (OPS code 5.384 for open aortic repair (OAR) and 5.38a* for endovascular repair (EVAR)) in those with a principal diagnosis AA.

Death rates caused by AA and AD were taken from the cause of the publically available death statistics. The cause of death statistics is an annual full survey. The data is based on the death certificates that are issued as part of the post-mortem examination. The parts of the death certificates intended for official statistics are evaluated. In principle, if information is missing or implausible, the health authorities are asked, which can clarify any discrepancies with the doctors. Failed responses are recorded as “unknown cause of death.”

Finally, we received a defined data set from the Federal Bureau of Statistics including information from all fully reimbursed inpatient cases with the principal diagnosis of AA and AD that received open (OAR) or endovascular aortic repair (EVAR) procedures. In addition, we received age-adjusted mortality rates per 100,000 inhabitants for the death causes AA and AD. Since we did not analyze the impact of other co-variables on mortality, we used linear regression analysis for statistical evaluation of the trends over the 11-year study period. Our statistical analysis is just descriptive. Calculations were done using Microsoft® Access 2003.

According to the occupational regulations for the North Rhine-Westphalian physicians, retrospective epidemiological research projects are specifically excluded from the necessity of an ethics vote. Specific linking of cases and procedures is possible but not allowed for legal reasons. Thus, institutional review board approval and patient’s informed consent are not necessary.

Results

From 2006 to 2017, the total number of patients admitted with the principal diagnosis of AA increased by 25.8% from 19,505 in 2006 to 24,529 in 2017 (Table 1) and that of AD by 56.7% from 4111 to 6443 (Table 2). Regarding the procedures, the number of AR by EVAR or OAR increased by 39.4% from 11,224 to 15,644 and that of AR of AD increased by 126.4% from 1288 to 2916 (Table 3).

Table 1.

Given are the total numbers of cases admitted to hospital with the principal diagnosis of AA separated for aortic segments and gender.

	2006	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016	2017
Males
*1, thoracic ruptured	332	300	338	341	352	384	349	307	346	346	340	329
*2, thoracic	2184	2389	2435	2629	2804	3101	3030	3331	3170	3325	3264	3199
*3, abdominal ruptured	1875	1946	1893	1890	1948	1758	1714	1772	1649	1723	1678	1812
*4, abdominal	10,240	10,875	10,970	11,140	11,673	11,804	11,825	11,713	12,027	12,141	12,062	11,975
*5, thoraco-abdominal ruptured	122	133	127	141	125	152	133	143	171	156	152	163
*6, thoraco-abdominal	460	548	496	533	535	686	747	859	872	972	1098	1243
*8, not localized ruptured	108	58	70	61	61	60	49	53	42	42	36	39
*9 not localized	289	219	245	220	233	198	156	166	159	153	127	142
Females
% of all	20.0	20.0	20.3	20.5	20.8	20.8	21.8	21.3	22.0	22.5	22.7	22.9
*1, thoracic ruptured	234	241	264	234	240	269	246	259	254	271	255	309
*2, thoracic	1191	1300	1406	1453	1649	1669	1728	1710	1881	1912	1971	1887
*3, abdominal ruptured	498	432	430	458	462	445	458	437	399	457	411	431
*4, abdominal	1505	1584	1585	1702	1734	1765	1965	1911	1974	2064	2034	2092
*5, thoraco-abdominal ruptured	82	93	76	80	83	99	82	91	96	112	126	91
*6, thoraco-abdominal	229	350	342	306	373	399	452	474	528	545	654	735
*8, not localized ruptured	30	29	23	33	32	31	21	18	16	21	18	24
*9 not localized	126	96	97	101	84	79	69	74	63	85	46	58
All	19,505	20,593	20,797	21,322	22,388	22,899	23,024	23,318	23,647	24,325	24,272	24,529

Table 2.

Given are the total numbers of cases admitted to hospital with the principal diagnosis of AD separated for aortic segments and gender.

	2006	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016	2017
Males
*00, not localized	267	231	209	231	205	209	251	230	245	204	221	268
*01, thoracic	1224	1352	1472	1504	1475	1410	1471	1588	1601	1570	1660	1669
*02, abdominal	144	151	216	188	233	235	212	247	270	272	268	299
*03, thoraco-abdominal	747	657	639	698	892	885	1006	1020	1036	1187	1245	1363
*04, ruptured not localized	28	41	46	48	48	36	41	31	42	41	41	44
*05, ruptured thoracic	221	278	279	270	293	289	330	283	348	336	370	355
*06, ruptured abdominal	41	50	55	58	47	49	52	52	48	58	50	36
*07, ruptured thoraco-abdominal	65	74	76	77	67	78	81	90	81	105	115	130
Females
% of all	33.4	33.6	33.6	32.9	33.5	34.1	33.7	35.9	34.4	37.1	36.1	35.4
*00, not localized	135	110	123	116	112	128	120	137	133	147	165	177
*01, thoracic	690	723	755	754	801	809	830	962	887	980	1040	1033
*02, abdominal	78	72	105	79	92	87	88	105	106	149	101	136
*03, thoraco-abdominal	282	277	286	310	372	391	429	467	481	590	572	568
*04, ruptured not localized	12	24	21	15	12	17	17	28	28	18	26	26
*05, ruptured thoracic	122	159	169	166	195	172	199	216	215	243	252	258
*06, ruptured abdominal	21	25	25	20	16	15	15	16	19	26	20	24
*07, ruptured thoraco-abdominal	34	45	27	48	42	32	54	53	56	68	70	57
All	4111	4269	4503	4582	4902	4842	5196	5525	5596	5994	6216	6443

Table 3.

Given are the total numbers of OAR and EVAR procedures in cases with the principal diagnosis of AA and AD.

Procedures	2006	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016	2017
AA
OAR	7794	8143	7507	7425	7220	6766	6197	5739	5744	5413	5190	5168
EVAR	3430	4158	4864	5907	6889	7814	8611	9147	9,558	10,095	10,338	10,476
All	11,224	12,301	1,2371	13,332	14,109	14,580	14,808	14,886	15,302	15,508	15,528	15,644
AD
OAR	960	1053	1159	1230	1291	1316	1401	1565	1568	1710	1784	1912
EVAR	328	357	400	417	492	527	644	756	803	850	955	1004
All	1288	1410	1559	1647	1783	1843	2045	2321	2371	2560	2739	2916

Number of deaths attributed to AA were 3687 in 2006 and 3807 in 2017 (+3.3%) and that to AD were 734 and 1236 (+68.4%). Age-adjusted death rates for AA decreased from 4.0 to 2.9 per 100,000 inhabitants and that for AD increased from 1.0 to 1.4 in this period (Table 4).

Table 4.

Given are the total numbers of death and the age-adjusted death rate per 100,000 attributed to AA and AD.

Death	2006	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016	2017
AA
absolute	3687	3645	3814	3690	3715	3666	3601	3602	3765	3725	3660	3807
Age-adjusted per 100,000	4	3.8	4	3.6	3.6	3.4	3.2	3.2	3.1	3	2.9	2.9
AD
Absolute	734	767	803	861	839	849	943	944	1047	1102	1114	1236
Age-adjusted per 100,000	1	1	1	1.1	1	1.2	1.2	1.1	1.3	1.3	1.3	1.4

The association between the decreasing age-adjusted death rate of AA and the increasing procedure rate cases can be described by linear regression as y = −0.0003*y + 6.7076 (p < 0.0001) (Figure 1). Accepting this association between procedures and AA, each 1000 procedures save 0.3 lives per 100,000 inhabitants. Based on around 80 million people in Germany, this would account for 240 lives per 1000 procedures, which represents a number to treat (NNT) of around 4.

Figure 1.

Given is the association between the absolute number of procedures and age-adjusted death rates attributed to AD and AA and the curves of linear regression.

The decrease in hospitalizations with rAA cases can be described by linear regression as y = −0.3771*year +772.66 (p < 0.0001). Linear regression for the rate of rAD can be described with y = −0.0139*year +42.75 (p=0.8473) (Figure 2). Therefore, there are different trends in the hospitalization rates of patients admitted for rAA and rAD. The rate of cases admitted with rAA decreased, whereas the rate of those with rAD remained unchanged from 2006 to 2017.

Figure 2.

Given are the rates of rAD and rAA of all cases admitted to hospital with the principal diagnosis of AD and AA for the years 2006–2017 and the curves of linear regression.

Using a linear regression model, the rate of rAA is estimated as 16.20% or 3159 hospitalized cases in 2006. Without elective AR, the rate of rAA cases should be similar in 2017 and would represent 3974 (16.2% of 24,529 cases) hospitalized cases with rAA. The difference of 776 cases hypothetically represents the number of cases prevented by elective AA repair. Since we observed 4229 additional elective ARs in 2017 compared to 2006, the number needed to treat (NNT) to prevent one hospitalization for rAA by elective AR of elective AA is determined to be 5.5. The increasing number of elective AR in cases with elective AD is not correlated with a decreasing rate of hospitalization for rAD. Therefore, an NNT cannot be calculated.

Discussion

This is the first study demonstrating against the background of general improvements in the care of aortic diseases such as screening, emergency care, and endovascular techniques; the increasing number of elective AR in the last decade correlates with a decreasing mortality rate for AA in Germany. Surprisingly, we were unable to demonstrate the same for AD.

Although there is a general increase in cases presenting with AA, the overall incidence of fatal rAA drastically decreased in the United States between 1999 and 2016,^5,6 Germany^24–26 and other countries.^7,8 Similar trends are reported for AD.^10,11,27 Based on the Global Burden of Disease Study Global Health Data Exchange abdominal AA death rates felt in 19 European countries in the last three decades, but slightly increased in 14 of these 19 countries beginning in 2012.²⁸ The shift from open AR to EVAR has been accompanied by decreasing periprocedural mortality.^29–32 The small increases observed in 14 of 19 EU countries among men and women during the most recent intervals analyzed (usually 2011–2012 to 2017) are most likely influenced by reintervention and/or late rupture, both well-described sequelae of EVAR.^33–36

Admissions for AD, especially thoracic AD, increased, but the overall in-hospital mortality rate among patients has decreased steadily over time.^10,12 Although the onset of AD as well as the disease is completely different compared to AA, the reasons for the decrease in mortality of both diseases remain speculative but are certainly multifactorial. Risk factor modification, improvement in regional centralization, adequate emergency preparedness, and improvement in surgical training and surgical and postsurgical care have all contributed to the decrease in incidence and mortality of both, but only AA can be treated prophylactically.

In our analysis, we looked for global trends in absolute hospitalizations of AA and AD cases and procedures. The absolute number of cases presenting with AA is higher compared to AD, but the relative increase from 2006 to 2017 was higher for AD, which is in line with the literature.^12,19 Absolute hospitalization rates for AA are primarily driven by non-ruptured AA, especially abdominal AA, which increased by 5024 from 2006 to 2017. Hospitalization rates for rAA remained almost unchanged in this period. The aging population, increasing awareness, and high reimbursement favoring treatment in case of diagnosis may explain increasing absolute hospitalization rates of non-ruptured AA in Germany. Age-standardized hospitalization rates remained almost constant. Screening programs were not established until 2017 in Germany. A recent report from the International Consortium of Vascular Registries including 11 countries with different reinbursement systems clearly indicated a tendency toward a lower threshold diameter for intact abdominal AA repair in fee-for-service countries like Germany.³⁷ Thus, the threshold for AAA therapy is rather low in Germany. Most likely this is due to our reimbursement system. Since EVAR is a much less invasive therapy with relatively low complication rates, AAA repair especially in fragile patients has increasingly be offered and performed over the last decade.

As we look on cases, repeated admissions or readmission for aortic disease are included, but do not contribute to this increase, relevantly. The number of hospitalized cases treated by EVAR or OAR increased from 57.5% in 2006 to 63.8% in 2017. A relevant number of repeated admissions or readmission should have decreased this rate because especially the OPS-Code for EVAR can only be documented once. The number of EVAR conversions to OAR is rather low, as recent studies reported.³⁸ Overall, aneurysm reintervention rates are reported with 4.1 and 1.7 per 100 person-years in the EVAR than in the OAR group.³⁹ Repeated admission for diagnostic reasons or endoleak treatment not covered by the considered OPS codes for EVAR or OAR was not incorporated in our analysis. Therefore, the effect of repeated admission is estimated with a value of 1–2% in the current study and therefore a negligible error.

Hospitalization rates for AD are driven by non-ruptured AD, especially thoracic and thoraco-abdominal AD, which increased by 2048 from 2006 to 2017, which is in line with the literature^40,41. Unfortunately, the ICD-10 coding does not reflect the more clinical and anatomic differentiation according to DeBakey in Types I, II, and III or Stanford classes A and B (16). In Type A AD, surgery is the treatment of choice to treat,^16,42 and in Type B AD - when uncomplicated - the patient can be safely stabilized. ICD-10 coding differentiates in ruptured and non-ruptured AD, whereas ruptured is defined as blood outside the vessel. As we include all cases with the principal diagnosis of AD, the different classifications are not relevant for our results.

Despite similar trends in hospitalization and treatment for AA and AD, age-adjusted mortality rates show contrasting trends in Germany during the last decade. Age-adjusted mortality rates for AA decreased, while mortality rates for AD increased. With our descriptive approach, we calculated the NNT to prevent an additional AA-related death in 2017 by increased application of AR compared to 2006 with around 4. We would like to clarify that this is not the absolute NNT but only the increase in NNT during the analyzed period. We do not know the NNT in 2006 and before. We did not analyze the effect of the shift from OAR to EVAR in this period on in-hospital mortality. This shift in treatment strategies definitely reduces mortality in people treated for non-ruptured AA. In-hospital mortality in cases with non-ruptured AA associated with EVAR is around 1% and with OAR around 5% during the last years.^32,43,44 Data regarding NNT for AR are rare. The main reason is that randomized controlled studies with untreated controls are ethically problematic. Looking at the 5-year survival, Miller et al.⁴⁵ reported an NNT of two for thoraco-abdominal aortic repair in 2004. They analyzed the 5-year survival of 1004 cases with aneurysms of the descending thoracic and thoraco-abdominal aorta treated in the period from 1991 to 2003. Natural history data for comparison were taken from a population-based epidemiological study of thoracic aneurysm incidence and survival conducted in Olmstead County Minnesota, using data from the Rochester Epidemiology Project, over a 30-year period published in 1982.⁴⁶ Large prospective screening studies reported benefits in terms of aneurysm-related deaths, not all-cause mortality.⁴⁷ We did not look for all-cause mortality and do not know how robust the presented NNT in our analysis is. Since we had no follow-up data, our approach is a different one. Our dataset shows that for AA and AD, the therapeutic approach has changed dramatically during the last decade. Due to the minimal invasive nature of EVAR more—especially fragile—patients are treated for AA. This might be the main reason for the increase of 25% in hospitalization rate over period. The increase of 57% in hospitalization rate for AD is not alone explainable by introduction of endovascular techniques, since the numbers for open and endovascular repair have been proportional in our analysis. We suspect that this increase is due to the increasing age of our general population, availability of CT-imaging, and an improvement in perioperative management, where many octogenarians are progressively eligible for such therapies.

Germany is a fee-for-service country, and number of prophylactic ARs is partly driven by reimbursement. Even in such a country, prophylactic AR of AA appears to be correlated with declining mortality with low NNT. This may be different in other countries with different reimbursement systems.

Strength and limitations

A major strength of this study is the large data set, which includes virtually all German hospitals and the observation period of more than 10 years. This allows a unique view at the current clinical practice.

The presented analysis is not an exact calculation, but the figures are quiet precise estimations of the size of effect of AR in this period. We are able to show the increase in numbers of OAR and EVAR procedures from 2006 to 2017 very exactly. The cause of death statistics is based on the death certificates. The exact circumstances that lead the diagnoses of AA or AD on the death certificate are unclear. It can be assumed that these diagnoses are only accepted as cause of death, if they have already been documented in the medical history before. To underline our results regarding AA and AD mortality, we looked for trends in hospitalization rates for rAA and rAD. These diagnoses are valid and based on imaging of the vascular system with admission to hospital. The NNT to prevent one hospitalization for rAA by elective AA repair was estimated to be 5.5. This is within the same dimension of that NNT to prevent mortality.

There are other factors limiting our results. First of all, our study design did not allow control for confounding including indications for treatment and quality of treatment. Second, the consequence of this approach is that we do not have information about the indications for treatment, quality of treatment, or any outcomes. Moreover, our data does not allow for cross-linking of diagnosis and procedures and adjustment for comorbidities. Third, the analysis is based on cases and not on individual patients. As a consequence, a patient could be included several times in the statistics, if he were hospitalized because of AA and AD at two different times within 1 year or had received EVAR first and OAR later. Fourth, although hospitalization rates are frequently used for secondary purposes, there is no systematic analysis of coding quality in Germany, and the agreement of coding and “reality” has yet to be investigated in controlled trials. Therefore, we cannot assess if and how coding errors may have impacted our analysis. But if the increase in AA cases seen in this study is simply a reflection of better coding overtime, it should have affected all AA ICD codes in a similar way. As one can see in Table 1, the increase was much higher for thoraco-abdominal AA than others.

In conclusion, despite increasing numbers of AR for AA and AD, only death rates for AA decreased in Germany. That of AD did not. As application of AR for AA in Germany increased—most-likely due to the increased application of EVAR—our analysis shows for the first time that the AA-related death rates decreased. We were able to estimate an NNT for AR of AA to prevent a death from AA or a hospital admission due to rAA with 4 and 5.5, respectively. Further studies are necessary to clarify why the increase in AR for AD has no effect on AD-associated mortality.

Footnotes

Acknowledgment

We thank Referat VIII A 1 from the Federal Statistical Office for extracting and providing the data from the DRG-Statistik.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Knut Kröger

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