Bare Metal vs Drug Eluting Stents

Should DES be the chosen one?

Class 22, 1st yearAdviser: Prof. Filipa Almeida

Authors: Aguiar, A.; Alves, R.; Baptista, M.J.; Domingues, A.; Durão, N.; Máximo, J.F.; Neto, N.; Pereira, S.; Pinto, D.; Rodrigues, I.; Sousa, D.

Summary

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Importance of the study

Cardiovascular diseases are the most common cause of death in Europe, being coronary disease (CD) the most frequent one1

The relevance of this study resides in the fact that there are no previous studies comparing the use of the two different types of stents in Portugal

A study based in the complications as well as success rates of bare-metal and drug-eluting stents could be significantly useful, since it would provide an evaluation on efficacy and costs.

[1] Rayner M, Allender S, Scarborough P. Cardiovascular disease in Europe. European Journal of Cardiovascular Prevention and Rehabilitation. 2009

Background

Research Question

Aims

Participants and Methods

Conclusion

Results

Coronary Disease

Occurs when the arteries that supply blood to the heart muscle (coronary arteries) become hardened and narrowed due to the build-up of cholesterol and other material, called plaque, on the inner walls of the arteries

Less blood may flow through the arteries consequently leading to the lack of oxygen in the heart muscle, causing chest pain (angina) and ultimately acute coronary syndrome (heart attack) 2

[2] Camm A, Luscher T, Serruys P. The ESC Textbook of Cardiovascular Disease.

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Percutaneous Coronary Intervention

Procedure in which a special tubing with an attached deflated balloon is threaded up to the coronary arteries 3

Balloon is inflated to widen blocked areas where blood flow to the heart muscle has been reduced or completely blocked

According to the Euro-Heart Survey 2006, in the great majority of situations (94%), PCI is combined with implantation of a stent 4

[3] American Heart Association. Cardiac Procedures and Surgeries - Nov 2010

[4] British Heart Foundation.[2008 May] Managing patients with coronary stents.

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Intracoronary Stenting (IS)

Stent: a tiny wire mesh tube that is left in the artery permanently to help maintain the artery unblocked and decrease

the chance of another blockage5

[5] Scholte op Reimer WJM, Gitt AK, Boersma E, Simoons ML (eds.). Cardiovascular Diseases in Europe.

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Intracoronary Stenting (IS)

There are two main types of stents currently in use 6:

[6] American Heart Association. Drug-eluting stents beat bare metal stents in diabetics

Background

Research Question

Aims

Participants and Methods

Results

Drug-Eluting(DES)

• Coated with a drug that fights the proliferation of cells that can block the artery

• Significantly reduce the need of repeated procedures

Bare-Metal(BMS)

• Made of stainless steel• Procedure involves

lower costs than with DES

Conclusion

Intracoronary Stenting (IS)

The relative percentages of the use of the two kinds of stents vary worldwide

Data from 2005/2006 5 , in Europe, showed a high use of DES in:◊ Switzerland 70%◊ United Kingdom 67%

On the contrary, Germany had the lowest percentage of use with only 21%

[5] Scholte op Reimer WJM, Gitt AK, Boersma E, Simoons ML (eds.). Cardiovascular Diseases in Europe.

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Research Question

What is the proportion of bare-metal and drug-eluting stents used in Portuguese patients over theperiod between 2006 and 2009 and what are the

complications associated to the use of each?

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Aims

Compare the CHD-associated complications or severity indicators, such as mortality of any cause, myocardial infarction and hospital readmission of patients admitted with acute coronary syndrome

Evaluate the rate of implantation of each of the two different types of stents - bare-metal and drug-eluting - during the period between 2006 and 2009, in angioplasties performed on the patients mentioned above

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Study Participants

The population with Coronary Heart Disease, as main diagnosis, living in the Portuguese mainland

The sample for the study is selected in a non-randomized, convenience manner from within an available clinical records database

Background

Research Question

Aims

Participants and Methods

Results

Patients with CD

Patients submitted to PCI

Intracoronary Stenting

(DES/BMS)

Conclusion

Study Participants

Inclusion Criteria

◊ All the state hospital admissions by cardiovascular disease, as main diagnosis, are selected according to the International Classification of Diseases 9th revision (ICD-9) codes

Exclusion Criteria

◊ All the admissions that do not contain the outcome information are excluded

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Study Design

Observational, retrospective and longitudinal, once the gap considered is between 2006 and 2009

The unit of observation is the population with CHD living in Portugal

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Data Collection Methods

The data was accessed from a database with records of all Portuguese State Hospitals, from 2000 to September of 2009

Available variables:

◊ Age◊ Sex ◊ Date of entry◊ Date of discharge◊ Diagnostics◊ Procedures◊ Result of admission (outcome)

Background

Research Question

Aims

Participants and Methods

Results

ICD-9 Codes Conclusion

Data Collection Methods

ICD-9 is an international standard diagnostic and procedures classification for health management purposes, epidemiological and clinical use

The codes for the cardiovascular procedures/technology are:

◊ 36.01 – 36.07 – Percutaneous coronary intervention◊ 36.07 – Drug eluting stent◊ 36.01, 36.06 – Bare metal stent

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Data Collection Methods

The ICD-9 codes for Diseases of the Circulatory system are:

IC9 - code Disease410 Acute myocardial infarction411 Other acute and subacute forms of

ischemic heart disease

412 Myocardial infarction413 Angina pectoris 414 Other forms of chronic ischemic heart

disease

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Statistical Analysis

Software used:◊ SPSS software (v. 19.0.0; SPSS Inc)

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

Statistical Analysis

The period between 2000 and 2005 was eliminated because it does not have comparable data

The patients implanted with both BMS and DES were excluded, since, in those cases, it would not be possible to relate the complications to one specific type

Background

Research Question

Aims

Participants and Methods

Epected ResultsResults

DES were introduced in Portugal in 2006

Conclusion

Statistical Analysis

The variables were analysed annually

◊ Comparison BMS vs DES in each year◊ Comparison of consecutive years for each type of stent

Significance for the entire statistical analysis was accepted at p < 0,05

Background

Research Question

Aims

Participants and Methods

Epected ResultsResults

Conclusion

Statistical Analysis

Categorical Variables Analyzed:

◊ Implantation of BMS or DES ◊ Myocardial Infarction (during hospitalisation)◊ Haemorrhagic complications ◊ Readmissions * (due to Ischemic Heart Disease)◊ Mortality

Background

Research Question

Aims

Participants and Methods

Percentage and Frequency

Chi-square Test

Results

* Analysed using the number of repeated episodes, for the same patient, in the same year and hospital (due to limitations on the database)

Conclusion

Statistical Analysis

Numerical Variable Analyzed:

◊ Period of hospitalisation(measured in days; cases whose number of days of hospitalisation assumed negative values in the database were dismissed )

Background

Research Question

Aims

Participants and Methods

Median

Percentiles 5 and 95

Mann-Whitney U

Test

Results

Conclusion

Results

Background

Research Question

Aims

Participants and Methods

Results

34 272 patients

25 666 8 605

Aged between 9 and 102 years (median= 64)

Conclusion

BMS vs DES

Background

Research Question

Aims

Participants and Methods

2006* 2007* 2008* 2009*

97,5%(7994)

75,7%(6565)

57,3%(5812)

57,1%(2300)

2,5%(207)

24,3%(2102)

42,7%(4186)

42,9%(1728)

BMS vs DES

BMS DES

Graphic 1: Percentage of implantation of each type of stent per year

Results

BMS were the most frequently apllied every

year

However, they were in a remarkable decline, giving

way to DES

* p < 0,05

Conclusion

BMS vs DES

Background

Research Question

Aims

Participants and Methods

Results

The obtained results agree with Spinler et al ‘s study that also states that the use of DES have been increasing since their introduction 7

In the last two years , the percentage of DES cases seems similar

This can be related to the fact that our statistical analysis does not include cases of simultaneous implantation of both BMS and DES

[7] ] Spinler SA. Percutaneous Coronary Intervention: Assessing Coronary Vascular Risk Associated With Bare-Metal and

Drug-Eluting Stents. Am J Manag Care. March 2009; 15(2 Suppl):S42-7

Conclusion

Period of Hospitalisation

Background

Research Question

Aims

Participants and Methods

Median:◊ BMS

4 days, in all 4 years

◊ DES2 days, 20061 day, 2007 and 20083 days, 2009

The median of the period of hospitalisation was lower in the DES than in the BMS in all 4 years (2006-2009)

Comparison using the Mann-Whitney U Test demonstrated that the difference is significant (p < 0,05)

Conclusion

Results

Period of Hospitalisation

Background

Research Question

Aims

Participants and Methods

The Percentile 5 was 0 days for every year analysed, for both BMS and DES

Percentile 95:◊ BMS

15 days, 2006 and 200714 days, 2008 and 2009

◊ DES14 days, 20069 days, 2007 12 days, 200813 days, 2009

BMS presented higher values than DES for the Percentile 95

Conclusion

Results

Period of Hospitalisation

Background

Research Question

Aims

Participants and Methods

Conclusion

ResultsThe implantation of DES has high costs, but this costs can be compensated by their small period of hospitalisation

The reason why this happens could be a motive for further studies, as there are not any known references about this particular matter

DES DES

Readmissions

Background

Research Question

Aims

Participants and Methods

2006*

2007*

2008*

2009

6,2%(493)

11,5%(758)

7,3% (408)

5,9% (136)

12,1%(207)

24,5% (516)

15,2% (635)

5,8% (101)

Readmissions

DES BMS

Graphic 2: Percentage of patients readmitted per type of stent and per year

Conclusion* p < 0,05

Results

DES displayed significantly higher

results between 2006 and 2008

Comparison between consecutive years, in each type of stent:

2006-2007

2007-20082008-2009

Readmissions

In a global vision, the percentage of readmissions decreases over the years, independently of the type of stent

Background

Research Question

Aims

Participants and Methods

Conclusion

Results

Why?

Improvement of PCI techniques

Evolution of post-surgical treatments

Haemorrhagic Complications

Background

Research Question

Aims

Participants and Methods

2006 2007 2008 2009

0,2%(18)

0,3%(19)

0,3%(18)(11)

0,4%(10)

0,0%(0)

0,2%(4)

0,8%(14)

Haemorrhagic Complications

BMS DES

Graphic 3: Percentage of patients who had haemorrhagic complications during hospitalization per type of stent and per year

Conclusion

Results

Higher percentage for BMS in the first 2 years

Same percentage for both in 2008

Higher percentage for DES in 2009

The Differences are not statistically significant

It can not be concluded that there is a link between the

type of stent implanted and the development of

haemorrhagic complications

Myocardial Infarction

Background

Research Question

Aims

Participants and Methods

2006*

2007*

2008*

2009

5,0%(403)

4,8%(312)

4,8%(289)

4,9%(113)

1,4% (3)

3,0% (63)

3,2%(133)

5,8%(101)

Myocardial Infarction

DES BMS

Graphic 4: Percentage of patients who had myocardial infarction during hospitalization per type of stent and per year

Conclusion

* p < 0,05

Results

BMS cases showed a higher incidence between

2006 and 2008

In 2009, the incidence increased in DES cases, being significant when compared with 2008

(p=0,003)

Myocardial Infarction

Background

Research Question

Aims

Participants and Methods

Conclusion

Results

The significant augment of myocardial infarction for DES in 2009 could be explained by the reduction of the sample size, comparing with the two previous years

Over-increased the percentages of both myocardial infarction and haemorrhagic complications for DES

Mortality

Background

Research Question

Aims

Participants and Methods

Results

2006 2007* 2008* 2009*

1,8% (143)

2,1% (140) 2,1% (119)2,2% (50)

1,9% (4)

0,5% (11)0,6% (26)

1,0% (18)

Mortality

BMS DES

Graphic 5: Percentage of patients deceased per type of stent and per year

Discussion

* p < 0,05

Mortality is significantly higher in BMS cases, with the exception of 2006

The difference in 2006 is not statistically

significant

Comparison of consecutive years, in each type of stent:

DES 2006-2007

Mortality

Background

Research Question

Aims

Participants and Methods

Results

Discussion

DES has a lower mortality rate than BMS

This result is supported by various works 8,9,10 and could be related to a long-lasting antiplatelet therapy associated to DES 9

The relevant decrease between 2006 and 2007 in DES mortality could be related to its recent introduction in Portugal , resulting in a very small sample on the first year

[8] Mauri L, Silbaugh TS, Wolf RE, et al. Long-Term Clinical Outcomes Following Drug-eluting and Bare Metal Stenting in Massachusetts. Circulation. 2008;118(18):1817-27.[9] Tamburino C, Salvo M, Capodanno D, et al. Are drug-eluting stents superior to bare-metal stents in patients with unprotected non-bifurcational left main disease? Insights from a multicentre registry. European Heart Journal. 2009; 30:1171-1179[10] Marroquin O, Selzer F, Mulukutla S, et al. A Comparison of Bare-Metal and Drug-Eluting Stents for Off-Label Indications. N Engl J Med. 2008; 358:342-352

The small augment in the mortality rate in 2009, though not significant, can be related to the similar increase in myocardial infarction for both types of stent

Limitations

Background

Research Question

Aims

Participants and Methods

Results

The non-inclusion of patients admitted and treated in private institutions/hospitals as well as in autonomous regions (Madeira and Azores)

Errors in the database (negative values for period of hospitalisation)

Exclusion of cases of simultaneous implantation of both BMS and DES

Conclusion

Limitations

Background

Research Question

Aims

Participants and Methods

Results

Readmissions are only considered for the same hospital, and in the same year(due to limitations on the database)

Co-morbidities that could act as confusion bias were not taken into account for any of the analysed variables (This is a pertinent limitation of this study, which may affect all available outcomes, with particular relevance for mortality 9 )

Conclusion

[9] Tamburino C, Salvo M, Capodanno D, et al. Are drug-eluting stents superior to bare-metal stents in patients with unprotected non-bifurcational left main disease? Insights from a multicentre registry. European Heart Journal. 2009; 30:1171-1179

Final Conclusions

Background

Research Question

Aims

Participants and Methods

Results

BMS have been the most frequently applied stents in Portugal

The use of DES has been rapidly increasing since 2006

DES show a lower percentage of mortality and myocardial infarction, and a shorter period of hospitalisation

DES show a higher percentage of readmissions

Conclusion

Final Conclusions

Background

Research Question

Aims

Participants and Methods

Results

Conclusion

No link was found between the development of haemorrhagic complications and the type of stent implanted

All in all, even though in a short-term analysis it can be concluded that DES are more beneficial than BMS, despite the higher costs, presently, we cannot make a long-term analysis to further study our economic objective

Acknowledgements

Background

Research Question

Aims

Participants and Methods

Results

Prof. Altamiro Pereira

Prof. Filipa Almeida

Prof. João Antunes

Prof. José Alberto Freitas

Conclusion