The use of reperfusion and revascularization procedures in acute coronary syndrome in Portugal: a systematic review

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Revista

Portuguesa

de

Cardiologia

Portuguese

Journal

of

Cardiology

www.revportcardiol.org

ORIGINAL

ARTICLE

The

use

of

reperfusion

and

revascularization

procedures

in

acute

coronary

syndrome

in

Portugal:

A

systematic

review

Luísa

Lopes-Conceic

¸ão

a,b

,

Marta

Pereira

a,b

,

Carla

Araújo

a,b,c

,

Olga

Laszcz´

ynska

a,b

,

Nuno

Lunet

a,b

,

Ana

Azevedo

a,b,∗

a_Department_of_Clinical_{Epidemiology,}_Predictive_Medicine_and_Public_Health,_University_of_Porto_Medical_School,_Porto,_Portugal b_EPIUnit_-_Institute_of_Public_Health,_University_of_Porto,_Porto,_Portugal

c_Centro_Hospitalar_de_{Trás-Os-Montes}_e_Alto_Douro_EPE,_Vila_Real,_Portugal

Received22March2013;accepted3November2013 Availableonline12November2014

KEYWORDS Acutecoronary syndrome; Angioplasty; Coronaryartery bypass; Fibrinolysis; Myocardial revascularization Abstract

IntroductionandObjectives:Reperfusion and revascularization therapies play an important roleinthemanagementofcoronaryheartdiseaseandhavecontributedtodecreasesincase fatalityrates.We aimedtodescribe theuseofthese therapiesfor thetreatment ofacute coronarysyndrome(ACS)patientsovertimeinPortugal.

Methods:PubMedwas searchedinJuly2012. Theproportion ofpatients treatedwith fibri-nolysis, primary percutaneous coronary intervention (PCI), any PCI and coronary artery bypassgrafting(CABG) was describedaccording totype ofACS:STEMI(≥90% patients with ST-segmentelevationorQ-wavemyocardialinfarction),NSTE-ACS(≥90%patientswith non-ST-segmentelevationACS)andmixedACS(allothers).

Results:We identified41 eligible studies, publishedbetween 1989 and 2011. Twenty-eight reportedonsamplesconsideredrepresentativeofACSpatientstreatedinPortugal.Thesmall numberofestimatesoftheuseofeachtreatmentinSTEMIandNSTE-ACSpatientsprecluded identificationofanytimetrend.Inthe last20 years,theproportionofmixedACSpatients treatedwithfibrinolysisdecreasedandtheuseofPCIincreased,whiletheuseofCABGdidnot change.

Conclusions:Thegeneralpatternoftheuseofreperfusionandrevascularizationisin accor-dancewith thatreportedin otherdevelopedcountries, reflectinga favorabletrend inthe qualityofcareofACSpatients.Therelativelysmallnumberofestimatesonthesame proce-dureincomparablepatientslimitsthegeneralizabilityoftheconclusions,andhighlightsthe needforsystematicapproachestomonitortheuseoftreatmentsovertime.

∗_{Corresponding}_author.

E-mailaddress:anazev@med.up.pt(A.Azevedo). http://dx.doi.org/10.1016/j.repc.2013.11.013

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PALAVRAS-CHAVE Síndromecoronária aguda; Angioplastia; Cirurgiade revascularizac¸ão coronária; Fibrinólise; Revascularizac¸ão miocárdica

Usodeprocedimentosdereperfusãoerevascularizac¸ãonasíndromecoronáriaaguda emPortugal:revisãosistemática

Resumo

Introduçãoeobjetivos:A reperfusãoerevascularizaçãodesempenhamum importantepapel notratamentodadoençacoronáriacontribuindoparaadiminuição daletalidade. Foinosso objetivodescrever ousodestes procedimentosnotratamentodasíndromecoronáriaaguda (SCA)aolongodotempoemPortugal.

Métodos:A pesquisa foi efetuada na Pubmed em julho de 2012. A proporção de doentes tratados com fibrinólise,angioplastia primária,qualquer tipode angioplastia ecirurgia de revascularização coronária(CABG) foi descritade acordocomo tipode SCA:SCA supra-ST (quandoaproporçãodedoentescomelevaçãodosegmentoSTouenfartedomiocárdiocom ondasQera≥90%), SCAsem-ST(quandoaproporçãodedoentescomSCAsemelevaçãodo segmentoSTera≥90%)eSCAmisto(restantescasos).

Resultados:Foramidentificados41estudospublicadosentre1989e2011.Vinteeoitoestudos descreveramamostras representativasdos doentes comSCA tratados em Portugal.Obaixo númerodeestimativasdecadatratamentonosdoentescomSCAsupra-STesem-ST, impossibi-litouaobservac¸ãodetendênciastemporais.Nosúltimos20anos,aproporc¸ãodedoentescom SCAmistotratadoscomfibrinólisediminuiu,ousodeangioplastiaaumentou,enquantoouso deCABGnãosealterou.

Conclusões:Opadrãodousodestestratamentosestádeacordocomdadospublicadosnoutros paísesdesenvolvidos,refletindoumatendênciafavorávelnaqualidadedoscuidadosprestados. Obaixonúmerodeestimativasdomesmoprocedimentolimitouageneralizac¸ãodeconclusões, reforc¸andoanecessidadedealternativasparamonitorizarousodetratamentosao longodo tempo.

Introduction

Coronary heart disease (CHD) is responsible for 7.3 mil-liondeathsyearlyworldwide,correspondingto12.8%ofall deaths.1_In_Portugal,_CHD_was_responsible_for_23%_of cardio-vasculardeathsin2009,2_though_mortality_rates_have_been decreasingsincethe1980s,asinmostdevelopedcountries.3 The increasing use of evidence-based treatments for acutecoronarysyndrome(ACS),includingreperfusion ther-apyandrevascularizationprocedures,hasbeenreportedto explain uptohalf of thedecrease in CHDmortality rates in several developed countries.4,5 _Continuous _and comp-rehensive monitoringof theuse of reperfusionand revas-cularization therapies for ACS patients in routine clinical practiceisthusessentialtoevaluatethequalityofcare.

The Portuguese Registry of Acute Coronary Syndromes provides data on a large number of ACS events in the last decade, but only patients admitted to some car-diology departments in the country are registered and consecutive recruitment is not ensured, possibly limiting itsrepresentativeness.6_Other_studies,_based_on_samples_of episodes,mainlysingle-centerandresultingfromthe initia-tiveoflocalphysiciansoracademicresearchers,havebeen publishedandcouldcomplementtheregistrydatawith cov-erageofother institutionsanddepartmentsandagreater timespan.

Therefore, we performed a systematic review of pub-lished studies reporting on the use of reperfusion and

revascularizationproceduresinpatientswithACSin Portu-gal.

Methods

Searchstrategy

WesearchedPubMedfrominceptionuntilJuly2012to iden-tify original reports providing data on the proportion of patientswithACS,stableanginaandheart failuretreated with pharmacological and non-pharmacological therapies in Portugal.The search expression is providedin the sys-tematic review flowchart (Figure 1). This report focuses on reperfusion and revascularization procedures in ACS. Thereferencelistsof reviewarticlesontreatment ofACS patientswerescreenedtoidentifyotherpotentiallyeligible originalstudies.

Screeningofreferencelists

Two reviewers independently assessed the studies in two steps,followingthesamepredefinedcriteria,todetermine theeligibilityofeachreport.Inthefirststepirrelevant stud-ies were excluded on the basis of the title and abstract only; when the abstract of a particular article was not available,thearticlewasselectedfor furtherassessment, exceptwhenthetitleunequivocallypresentedevidencefor

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682 publications

(626 identified through PubMed search and 56 from bibliographics references of reviews)

humans[mesh] AND (portugal[ad] OR portugal OR “acta med port”[journal] OR “rev port cardiol”[journal] OR “rev port cir cardiotorac vasc”[journal] OR lisboa[ad] OR lisbon[ad] OR (porto[ad] NOT (brasil[ad] OR brazil[ad] OR faro[ad] OR gaia[ad]) AND (“ischemic heart disease” OR “coronary artery disease”[mesh] OR “coronary heart disease” OR “acute coronary syndrome”[mesh] OR “myocardial infraction”[mash] OR “acute myocardial infraction” OR “angina pectoris”[mesh] OR “angina, unstable”[mesh] OR “stable angina” OR “chronic angina” OR angor OR “heart failure”[mesh]) AND (hospitalization[mesh] OR (therapeutics[mesh] OR treatments OR drug OR medication) OR “myocardial revascularization”[mesh] OR (“coronary artery bypass graft” OR cabg) OR (angioplasty, balloon[mesh] OR ptca OR “percutaneous transluminal coronary angioplasty” OR “primary angioplasty”) OR “hospital resuscitation” OR (thrombolysis OR “fibrinolytic agents”[pharmacological action] OR actilyse OR streptase OR rapilysin OR metalyse) OR aspirin[mesh] OR (“adrenergic beta-antagonists”[pharmacological action] OR “beta blockers”) OR (“ace inhibitors” or “angiotension-converting enzyme inhibitors”[pharmacological action]) OR “platelet iib/iiia inhibitors” OR

clopidogrel[substance name] OR heparin[mesh] OR “platelet aggregation inhibitors"[pharmacological action] OR statins OR warfarin[mesh] OR spironolactone[mesh] OR rehabilitation OR “angiotensin ii type 1 receptor

blockers"[pharmacological action] OR (“resynchronization therapy” OR “cardiac resynchronization therapy” OR crt OR ''biventricular pacemaker”) OR (“implantable cardiodefibrillator” OR “implantable cardio defibrillator” OR “implantable cardiac defibrillator”) OR “implantable cardioverter defibrillator” OR icd) OR (heart transplant* OR heart

transplantation[mesh terms] OR “allogeneic graft”) OR Cardiac Surgical Procedures[mesh]) AND (english[lang] OR spanish[lang] OR portuguese[lang])

Reasons for exclusion from the study:

• not involving humans – 6 • case reports-58

• reviews, editorials or comments – 244 • not involving Portuguese hospitals – 46 • patients' selection dependent on having undergone some diagnostic or treatment under study – 75

• not providing data on treatments – 110 • insufficient information to characterize the population – 10

• data described in other reports on the same studies – 53

Reasons for exclusion from this analysis: • data only on stable angina – 3 • data only on heart failure – 29

• no data on reperfusion or revascularization - 7

80 publications

41 publications with data on reperfusion and/or revascularization therapies * (28 unselected )

21 studies with data on reperfusion therapy

(12 unselected)

28 studies with data on revascularization therapy (22 unselected) 20 studies with data on fibrinolysis (12 unselected) Number of studies : total (unselected) STEMI – 6 (3) Mixed ACS – 14 (9) 5 studies with data on primary PCI

(4 unselected) Number of studies : total (unselected) STEMI – 3 (2) Mixed ACS – 2 (2) 24 studies with data on PCI (21 unselected) Number of studies : total (unselected) STEMI – 3 (2) NSTE-ACS – 9 (8) Mixed ACS – 14 (13) 20 studies with data on CABG (15 unselected) Number of studies : total (unselected) STEMI – 1 (1) NSTE-ACS – 10 (8) Mixed ACS – 12 (8)

Figure1 Flowchartofthesystematicreview.CABG:coronaryarterybypassgrafting;PCI:percutaneouscoronaryintervention; STEMI:90%ormorepatientswithdiagnosisofST-segmentelevationmyocardialinfarctionorQ-wavemyocardialinfarction; NSTE-ACS:90%ormorepatientswithdiagnosisofnon-ST-segmentelevationACS;mixedACS:mixtureofpatientswithseveraltypesofACS. *Ifastudyprovideddataontreatmentwithbothreperfusionandrevascularization,itcontributedtobothgroups.Ifastudy provideddataonmorethanonediagnosticcategory,itcontributedtoallgroups.

†_The_sample_was_considered_selected_when_inclusion_of_patients_was_dependent_on_having_undergone_some_diagnosis_or_treatment procedure;otherwise,itwasconsideredunselected.

exclusion (e.g. case report). The full texts of studies selectedforthesecondstepwerethenassessedtodecide ontheireligibilityandavailabilityofrelevantdata.

The decisions made independently by the two review-ers were compared in the two phases and disagreements wereresolvedbyconsensusorafterdiscussionwithathird researcher,ifnecessary.

The criteria for exclusion of studies were the follow-ing: not involving humans (e.g. in-vitro studies; animal research);case reports; reviews, editorialsor comments; not involving Portuguese hospitals; involving ACS patients whoseselectionwasdependentonhavingundergonea par-ticular diagnosis or treatment procedure understudy and withnoinformationonanyother procedure(e.g.samples

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includingonly patientswhounderwentPCI); notproviding dataon treatmentsin ACS patients; providinginsufficient informationtocharacterizethepopulation(e.g.not provid-inginformationonpatients’ageorsex,orsamplesize).

When more than one study provided data on patients withthesamediagnosis, selectedusingthesamecriteria, fromthe same institution and in overlapping periods, we included theone thatcoveredthe longest timeperiod;if the same time period was considered, the one with the largestsamplesizewasincluded,orincasesofsimilar sam-plesize,theonethatprovidedinformationonmoreeligible treatments. When there were two studies that included ACS patients admitted to the same hospital with part of the data collection period overlapping, we included only the one with the larger sample size, even though over a shorter timeperiod,7 _since_the _other _included _a _group selected from all patients with ACS.8 _When _two publica-tionsstudiedthesamesample,butreportedcomplementary resultsoneligibletreatments,both articleswereincluded but the information on each eligible treatment for each specific diagnosis was considered only once in the data analyses.

Dataextraction

Paperswerescrutinizedusingastandardizeddataextraction sheet, tocollect information on:first author, publication year,yearorperiodofdatacollection,geographical cover-ageanddepartmentwherepatientswererecruited,sample characteristics(studypopulation,diagnosis,typeofepisode [firstvs.recurrent],sex, ageandsamplesize),proportion of patientswhoreceived treatments(fibrinolysis, primary andnon-specified PCI andcoronary arterybypassgrafting [CABG]). If only the absolute number of patients treated was available, the proportion was calculated by dividing by thestratum-specific sample size.When an article pre-senteddatastratifiedbyavariablewithnorelevancetoour analysis (e.g. diabetic vs. non-diabeticpatients), we cal-culated the weighted average of the proportions over all strata.

AlltypesofPCI(includingprimaryPCI)wereconsidered intheanalysisofthisprocedureasrevascularization ther-apy. The proportions ofpatients undergoingpercutaneous and surgical revascularization procedures were described only whenperformed during theinitial hospitalizationfor theacuteevent. Weconsidered twotypes ofstudy popu-lationintermsoftheirrepresentativenessofACSpatients treatedin Portuguese institutions:when patientselection was dependent on having undergone a treatment or a diagnostic procedure (e.g. patients referred for viability tests;patientsundergoingcoronaryangiography),the popu-lationwasconsideredselected;otherwise,itwasconsidered unselected.

When possible, year-, sex-, age- and diagnosis-specific estimateswereextracted.

Dataanalysis

AllstudiesaredescribedintheSupplementaryTable avail-able online; only those relying on unselected samples of patients are represented in the forest plots. Although

sex- and age-specific estimates were extracted and are showninthedetailedSupplementaryTable,thesewere sel-dom availableandfor descriptivepurposestheresults for thetotal samplearealwayspresented intheforestplots, stratifiedonlybydiagnosis.

The proportion of patients who underwent each pro-cedure wasdescribed according totypeof ACS. However, giventhatreportsdidnotsystematicallystratifyaccording to thiscriterion, patientsamples wereclassified intoone ofthefollowingthreecategories,accordingtothe propor-tionofdifferentACSpatientsincluded:STEMI(90%ormore patientswithadiagnosisofST-segmentelevationmyocardial infarction (STEMI) or Q-wave myocardial infarction [MI]), NSTE-ACS (90% or more patients witha diagnosis of non-ST-segment elevationACS [NSTE-ACS]), and mixedACS (if neitherofthesecriteriawassatisfied).

Results

We identified 41 eligible studies providing data on ACS patients whounderwentreperfusionand/or revasculariza-tiontherapies,21presentingdataonreperfusionand28on revascularization (Figure 1), published between 1989 and 2011(SupplementaryTable1,availableonline).

Over three-quarters of the studies reported datafrom a singleinstitution, mainly fromthe Lisbon region.Three studieswerebasedonnationalregistriesthatcovered sev-eralregionsofthecountry.6,9,10_The_vast_majority_of_studies recruitedpatientsincardiologydepartments.Two-thirdsof thestudiesincludedunselectedpopulations.Morethanhalf of the studies included both first and recurrent episodes andfourstudiesreportedexclusivelyonfirstepisodes.11---14 The sample size ranged from 21 to 22482 patients, and almost 40% of the studies involved samples between 100 and 500 patients. Seven samples included mostly STEMI patients, 10 mostly NSTE-ACS patients and 27 a mixture of patients with several types of ACS. Five studies pre-sentedsex-specificestimates,10,14---17_and_only_two_presented age-specific estimates18,19 _{(Supplementary} _Table _1, avail-ableonline).

As expected, data on reperfusion were available only for STEMI and mixed ACS patients (Figure 1). Only three studies provided estimates of the use of reperfusion in STEMIpatients.Inmorerecentyears,onestudyconducted in Faro reported the use of fibrinolysis in 16.5% of STEMI patients in 2008,20 _while _a _report_from _the _National Reg-istryofAcuteCoronarySyndromesshowedameanof43.7%, representing many cardiology centers across the country over several years.6 _The _same _two _studies _reported _the use of primary PCI in 41.4% and19.2% of STEMI patients, respectively.6,20 _For_mixed_ACS_patients_there_was_a_larger numberofobservations;fibrinolysiswasusedinaquarterto ahalfofpatientsinthelate1990s,decreasingtolessthan 10% overthenextdecade.Tworeportspublished10years apart,in 2001and2011, showedan increaseintheuseof primaryPCIinmixedACSpatients,fromlessthan10%ina sample of patients fromseveral cardiology centersacross the country10 _to_{approximately} _50% _in _a_single _cardiology centerinLisbon19₍_Figure₂_).

Percutaneous revascularization, including both emer-gentandelective proceduresduringhospitalizationfor an

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First author, publication year Geographical coverage Episode type

Male, % Age*, yrs Sample

size

Proportion of patients treated, %

STEMI Caires G, 2000 Trigo J, 2008 Santos JF, 2009 STEMI Trigo J, 2008 Santos JF, 2009 MixedACS Ribeiro H, 1995 Fernando PB, 1996 Carôla B, 1996 Silva P,1997 Caires G, 1998 Bettencourt P, 2000 Morais J, 2001 Timóteo AT, 2011 Piçarra BC, 2011 MixedACS Morais J, 2001 Timóteo AT, 2011 V.F.Xira Porto Lisboa Lisboa Gaia Carnaxide Porto Portugal Lisboa Évora F+R F+R F+R F+R F 65 (13) 907 278 278 10.212 10.212 68 (14) 65 (14) 68 (14) 65 (14) 66 65.7 76.2 65.7 76.2 81 67 73 86.1 82.5 84.2 72.9 69.2 72.9 69.2 55.3 F F+R F+R F+R F+R F+R F+R F+R F+R -Funchal Faro Faro Portugal Portugal Portugal 61.8 (11.4) 62.2 (13.7) 64 (12) 57.5 21 191 1.319 504 178 101 1.366 1.242 1.366 1.242 132 0 10 20 30 40 50 60 70 80 90 0 10 20 30 40 50 60 70 80 90 56 (12) 58.3 (12.6) 65.1 (12.9) 65.1 (12.9) 64.2 64.2 83.2 (2.8) Fibrinolysis Primary PCI

Figure2 Proportionofacutecoronarysyndromepatientstreatedwithreperfusion therapies(fibrinolysis andprimaryPCI)in Portugal,estimatedinunselectedsamplesofpatients.F:firstepisode;mixedACS:mixtureofpatientswithseveraltypesofACS; NSTE-ACS: 90%or more patients withdiagnosis ofnon-ST-segment elevation ACS;PCI: percutaneouscoronaryintervention;R: recurrentepisode;STEMI:90%ormorepatientswithdiagnosisofST-segmentelevationmyocardialinfarctionorQ-wavemyocardial infarction.*Ageispresentedasmean(SD)unlessotherwisespecified;†_mean_age;‡_median_age.

First author, publication year Age*, yrs Episode type Male, % Sample size PCI, % Geaographical coverage STEMI 65.7 68 (14) 278 76.2 65 (14) 10.212 NSTE-ACS 82.6 56 (9) 132 Abreu P, 1993 71 65 55 Fernandes A, 1993 80 64 (11) 387 Timóteo AT ,2003 68.3 69 802 Teixeira R, 2009 66.6 68 (12) 9.314 Santos JF, 2009 Santos JF, 2009 68.3 65 (12) 2.956 81 63.7 (10.9) 389 Calé R, 2010 80.1 66.4 (10.6) 614 Raposo L, 2010 77.4 64.0 (10.5) 234 Carmo P, 2011 MixedACS 67 62.2 (13.7) 191 Fernando PB, 1996 82.5 56 (12) 178 Caires G, 1998 72.9 65.1 (12.9) 1.366 Morais J, 2001 0 43 33 Adão L, 2004 77.2 57.0 104 Sampaio F, 2006 73.7 64.1 (12.8) 589 Nabais S, 2008 68 65 (14) 368 Timoteo AT,2008 72.3 64.5 1.228 Gaspar A, 2009 69.6 66 (13) 22.482 Santos JF, 2009 70.1 67.0 (12.6) 1.296 Teixeira R, 2010 Teixeira M, 2010 94 40 (3.9) 128 69.2 64.2 1.242 Timóteo AT, 2011 Timóteo AT, 2011 69 64 (13) 1.126 0 10 20 30 40 50 60 70 80 90 Trigo J, 2008 Santos JF, 2009 Faro F+R F+R -F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R Lisboa Coimbra Coimbra Portugal Portugal Portugal Portugal Portugal Carnaxide Carnaxide Carnaxide Carnaxide Carnaxide Carnaxide Porto Gaia Gaia Braga Braga Lisboa Lisboa Lisboa S.M.Feira

Figure 3 Proportion ofacute coronarysyndromepatients treatedwith PCI inPortugal, estimated inunselected samples of patients.F:firstepisode;mixedACS:mixtureofpatientswithseveraltypesofACS;NSTE-ACS:90%ormorepatientswithdiagnosis ofnon-ST-segmentelevationACS;PCI:percutaneouscoronaryintervention;R:recurrentepisode;STEMI:90%ormorepatientswith diagnosisofST-segmentelevationmyocardialinfarctionorQ-wavemyocardialinfarction.*Ageispresentedasmean(SD)unless otherwisespecified;†_mean_age;‡_median_age.

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First author,

publication year Age*, yrs Samplesize

CABG, % STEMI Santos JF, 2009 Portugal F+R -F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R F+R Portugal Portugal Portugal Portugal Calé R, 2010 Raposo L, 2010 Carmo P, 2011 Carnaxide Carnaxide Carnaxide Carnaxide Carnaxide Carnaxide Abreu P, 1993 Fernandes A, 1993 Timóteo AT,2003 Timóteo AT, 2006 Nabais S, 2008 Gasper A, 2009 Santos JF, 2009 Teixeira R, 2009 Teixeira R, 2010 Teixeira M, 2010 Santos JF, 2009 Santos JF, 2009 NSTE-ACS Lisboa Coimbra Lisboa Braga Braga Coimbra S.M.Feira Episode type Male, % Geaographical coverage Mixed ACS Caires G, 1998 Morais J, 2001 82.6 56 (9) 132 71 65 55 80 64 (11) 387 68.3 69 802 66.6 68 (12) 9.314 68.3 65 (12) 2.956 81 63.7 (10.9) 389 80.1 66.4 (10.6) 614 77.4 64 (10.5) 234 82.5 56 (12) 178 72.9 65.1 (12.9) 1.366 73.7 64.1 (12.8) 589 68 65 (13) 368 72.3 64.5 1.228 69.6 66 (13) 22.482 70.1 67.0 (12.6) 1.296 94 40 (3.9) 128 76.2 65 (14) 10.212 0 10 20 30 40

Figure4 Proportion ofacutecoronarysyndromepatients treatedwith CABGinPortugal,estimatedinunselectedsamples of patients.CABG:coronaryarterybypassgrafting;F:firstepisode;mixedACS:mixtureofpatientswithseveraltypesofACS; NSTE-ACS:90%ormorepatientswithdiagnosisofnon-ST-segmentelevationACS;R:recurrentepisode;STEMI:90%ormorepatientswith diagnosisofST-segmentelevationmyocardialinfarctionorQ-wavemyocardialinfarction.*Ageispresentedasmean(SD)unless otherwisespecified;†_mean_age;‡_median_age.

acuteevent,wasperformedinapproximatelyhalfofSTEMI patientsaccordingtoareportfromFaroin200820 _and_the reportoftheNationalRegistryofAcuteCoronarySyndromes coveringseveralyearsandcentersacrossthecountry.6_For NTSE-ACS,twostudiespublishedin1993reportcontrasting experiences in small single-center samples, while from 2003 to 2011 several estimates consistently point to one third to one half of patients being revascularized percu-taneously during the acute hospitalization, withno clear timetrend.Withalargernumberofreportsandmore reg-ular publication over 15 years, the proportion of mixed ACSpatientsrevascularizedpercutaneouslyincreasedfrom under10%inthemid-1990stoapproximately70%inrecent years(Figure3).

CABG was used in 1.0% of STEMI patients (this figure available only from the National Registry of Acute Coro-nary Syndromes). In NSTE-ACS and mixed ACS, 1---10% of patientswerereportedasundergoingCABG,withnoclear timetrend.Anexceptionforseveralreportsisasingle insti-tution(HospitaldeSantaCruz,inCarnaxide)overtheyears, withaproportioncloserto20%ofNTSE-ACSpatientshaving undergonesurgicalrevascularizationduringhospitalization fortheacuteevent(Figure4).

Discussion

Despiteconsiderableheterogeneityinthemethodologyand presentation of results of available studies, this review showsthattheproportionofACSpatientsinPortugaltreated withfibrinolysishasdecreasedinthelast20yearsandthe use of PCI has increased, while the use of CABG has not changed.

Since the late 1970s, more aggressive and effective treatmentshavebeen developedandimplementedforthe treatmentofCHD,includingfibrinolysis,PCIandCABG.21_Of

theprimarystudiesincludedinthepresentreview,the old-estwithdataonfibrinolysiswaspublishedin1989,22 _while PCI andCABGwerefirstmentioned inanarticlepublished in1993(datacollectionin1982).23_Data_from_previous_years were reportedina fewpublications whichwere excluded mainlyduetothereportingformat,forexamplelackofdata onsamplesizeorpatients’sexandage,orbecausetheuse ofproceduresintheacutehospitalizationorovervariable follow-upperiodscouldnotbedistinguished.

Duringthelastdecade, mechanical orpharmacological reperfusiontherapyhasbeenrecommendedforallpatients with STEMI who present within 12 hours of the onset of symptoms.24---26_A_growing_body_of_evidence_has_also demon-stratedbeneficialeffectsofreperfusiontherapyinpatients presentingmorethan12hoursfromsymptomonset.Inthis group of patients, recent recommendations consider this treatment a strong indication, preferably by primary PCI (classI)ifthereis evidenceofongoing ischemiaor ifpain and electrocardiographic changes have been stuttering. PrimaryPCI maybealsoconsidered evenin asymptomatic patients presenting 12---24 hours after symptom onset.25 Foryears,fibrinolysiswaschosenoverprimaryPCI,mainly due to its greater ease of access and use.21 _However, mechanical reperfusion has been preferred since several randomized clinical trials and meta-analyses comparing primaryPCIwithin-hospitalfibrinolytictherapyinpatients presenting within 6---12 hours of symptom onset showed more effective restoration of vessel patency, less reoc-clusion, reinfarctionand stroke,improved leftventricular functionandlessshort-termmortalitywithprimaryPCI.27,28 National6,29 _and _{international} _registries _in _Europe30,31 and the USA32,33 _suggest _an _increase _in _the _use _of reper-fusion therapies accompanied by a significant shift from fibrinolysis therapy toprimary PCI. A significant decrease in mortality after STEMI has been observed in countries

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switching from fibrinolysis to primary PCI.34 _In _our _study, we observed decreased use of fibrinolysis and increased use of primary PCI. In this review, most of the studies providingdataonfibrinolysis werepublishedinthe1990s, withdatacollectedinthe1980sand1990s.Bycontrast,the studies addressing primaryPCIwere onlypublishedin the currentcentury.Althoughthetrendscannotbequantified, fibrinolysisappearstohavebeenreplacedbyprimaryPCI.

Sinceitsintroduction in 1977, angioplasty has become the most frequently performed major intervention in medicine,35_as_both_a_reperfusion_(primary_PCI)_and revascu-larizationprocedure.Amongtheincludedstudiesaddressing theuseofrevascularizationbyapercutaneous procedure, one sixthwere publishedin the 1990sand the remainder afterwards. Surgical revascularizationwithCABGwasfirst introducedin1969,andbecomethemostthoroughly stud-ied procedure in the history of surgery.36 _In _our _review, a quarter of the studies werepublished in the 1990sand the remainder after 2000. Although the primary studies provided information on surgeries performed at different times related to the acute event (e.g. during a variable timeoffollow-upaftertheacuteevent),weonlyincluded studieswithdataonCABGperformedduringtheinitial hos-pitalization.Otherwise,thedatatobecomparedwouldbe evenmoreheterogeneous. Particularlyforthis procedure, it is important to point out that many patients referred for CABG are expected to have undergone surgery after discharge or have been transferred to a different insti-tution while awaiting the procedure,6 _thus _reducing _the proportionof patients treatedthat werecapturedby this analysis.

Theresultsonrevascularizationtherapiesareconsistent withthefindingsofpreviousstudiesshowinganincreasein PCIuseandnon-significantchangesinuseofCABGinrecent years.30,37,38_In_patients_stabilized_after_an_episode_of_acute coronarysyndrome,thechoiceofrevascularization modal-itycanbemadeasinstablecoronaryheartdisease.25,39,40_In single-vesseldisease,whichoccursinone-thirdofpatients with ACS, ad-hoc PCI is feasible in most cases, whereas inpatientswithmultivesseldisease(approximately halfof cases)thedecisiononthetypeofrevascularizationismore complex.41,42 _Options_for _this_condition _have _evolved_over time,and currentlyinclude culpritlesionPCI, multivessel PCI,CABGorhybrid(combined) revascularization, accord-ingtoclinicalstatus,lesioncharacteristicsandtheseverity anddistributionofcoronaryarterydisease.25,39,40

Our methodology has some limitations. The use of a singlesearchenginemayhavelimitedourresults.However, theinclusionofrelevantstudiesidentifiedinthereference listsofthereviewarticlesshouldhavehelpedidentifyolder and non-PubMed-indexed publications. The probability of identifying relevant studies from among those published is also influenced by their results because, despite the descriptive nature of the studies, publication bias can be expected, with higher likelihood of publication from higher-quality or at least higher-volume centers. It is noteworthy thatthemajority of studiescame from cardi-ologydepartments,some ofwhichalsocontributedtothe NationalRegistryofAcuteCoronarySyndromes.Therefore, themaingainwiththisreviewisitscoverage ofagreater time span, but notthe representationof less specialized centers than those included in the National Registry of

AcuteCoronarySyndromes.Theresultsareaffectedbythe methodological heterogeneity of the studies, particularly inclusioncriteria, sample size,andpatients’age andsex, as well as the relatively small number of estimates for eachtypeoftreatmentunderstudy.Anotherlimitationfor moreinformativeconclusionsstemsfromthesmallnumber ofstudies withsex-, age-,andyear-specific estimates, as authorsmainlyreportedoveralldata.Some reporteddata referringtoaperiodlongerthanoneyear;however,itwas notpossibletoobtainyear-specificestimates.

Given these limitations, an alternative approach tothestudyoftrendsintheuseofthesetreatmentsinthe past could be to rely on administrative databases, using data collected, coded and stored, immediately available foranalysis.43_The_national_register_of_hospital_discharges29 could be used to quantify the number of procedures performed,buttheusefulnessofthesedatasetsislimited: itisnotpossibletoclassifythesubtypesof ACSaccording to current recommendations44 _when _departing _from _data coded using the International Classification of Diseases, 9threvision,ClinicalModification(ICD-9-CM).Furthermore, thereisnoinformationavailableinthedatabaseto ascer-tainthetiming ofPCI or toidentifyrecurrentepisodesin thesamepatient.29

Conclusions

Thegeneralpatternoftreatmentreflectswhatisreportedin otherdevelopedcountriesandcanbeviewedasafavorable timetrend in the qualityof care of ACS patients. Future investigationshould focusontheprospective and system-atic recording of high-quality information to monitor the useoftreatmentsinthisacutecondition,whilepasttrends canonly beproperlyclarified by anoriginal retrospective studyonarepresentativesampleofACSpatients,involving reviewofhospitalrecords.

Ethical

disclosures

Protection of human and animal subjects.The authors declarethatnoexperimentswereperformedonhumansor animalsforthisstudy.

Confidentialityofdata.Theauthorsdeclarethatnopatient dataappearinthisarticle.

Right to privacy and informed consent.The authors declarethatnopatientdataappearinthisarticle.

Funding

This study was funded by a grant from Fundac¸ão para a CiênciaeaTecnologia(PIC/IC/83006/2007).

Conflicts

of

interest

(8)

Acknowledgments

The authors gratefully acknowledge the contribution of authors whoprovided data different fromthat presented intheiroriginalreports,whichwereimportantfordecisions ofselectionandpresentationofdatainouranalysis.

Appendix

A. Supplementary

data

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.repc. 2013.11.013.

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