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Association Between Timeliness of Reperfusion Therapy and Clinical Outcomes in ST-Elevation Myocardial Infarction

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Association Between Timeliness of Reperfusion Therapy and Clinical Outcomes in ST-Elevation Myocardial Infarction ORIGINAL CONTRIBUTION Association Between Timeliness of Reperfusion Therapy and Clinical Outcomes in ST-Elevation Myocardial Infarction Laurie Lambert, PhD Context Guidelines emphasize the importance of rapid reperfusion of patients with Kevin Brown, MSc ST-elevation myocardial infarction (STEMI) and specify a maximum delay of 30 min- Eli Segal, MD utes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI). However, randomized trials and selective registries are limited in their ability to assess James Brophy, MD, PhD the effect of timeliness of reperfusion on outcomes in real-world STEMI patients. Josep Rodes-Cabau, MD Objectives To obtain a complete interregional portrait of contemporary STEMI care Peter Bogaty, MD and to investigate timeliness of reperfusion and outcomes. Design, Setting, and Patients Systematic evaluation of STEMI care for 6 months OTH PRIMARY PERCUTANEOUS during 2006-2007 in 80 hospitals that treated more than 95% of patients with acute coronaryintervention(PPCI)and myocardial infarction in the province of Quebec, Canada (population, 7.8 million). fibrinolysis are well-recognized treatmentsforST-segmenteleva- Main Outcome Measures Death at 30 days and at 1 year and the combined end point of death or hospital readmission for acute myocardial infarction or congestive Btion myocardial infarction (STEMI) in in- heart failure at 1 year by linkage to Quebec’s medicoadministrative databases. ternational guidelines, and benefits are 1,2 Results Of 1832 patients treated with reperfusion, 392 (21.4%) received fibrinoly- maximizedwhentreatmentoccursearly. Ͼ Although meta-analyses of randomized sis and 1440 (78.6%) received PPCI. Fibrinolysis was untimely ( 30 minutes) in 54% and PPCI was untimely (Ͼ90 minutes) in 68%. Death or readmission for acute myo- clinical trials support the superiority of cardial infarction or heart failure at 1 year occurred in 13.5% of fibrinolysis patients 3 PPCI over fibrinolysis, the generalizabil- and 13.6% of PPCI patients. When the 2 treatment groups were combined, patients ityoftheseresultstoeverydayclinicalprac- treated outside of recommended delays had an adjusted higher risk of death at 30 tice may be compromised by the highly days (6.6% vs 3.3%; odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21-3.93) selective recruitment of both patients and and a statistically nonsignificant increase in risk of death at 1 year (9.3% vs 5.2%; centers in these trials and the inability to OR, 1.61; 95% CI, 1.00-2.66) compared with patients who received timely treat- assess the effect of timeliness of treatment ment. Patients treated outside of recommended delays also had an adjusted higher onoutcomesbecauseofthegenerallyrapid risk for the combined outcome of death or hospital readmission for congestive heart failure or acute myocardial infarction at 1 year (15.0% vs 9.2%; OR, 1.57; 95% CI, performance of PPCI.3,4 In STEMI regis- 1.08-2.30). At the regional level, after adjustment, each 10% increase in patients treated tries, the observed delays for PPCI often within the recommended time was associated with a decrease in the region-level odds largely exceed those realized in clinical of overall 30-day mortality (OR, 0.80; 95% CI, 0.65-0.98). trials,5-7 and a substantial proportion of Conclusion Among patients in Quebec with STEMI, reperfusion delivered outside patients do not receive either PPCI or fi- guideline-recommend delays was associated with significantly increased 30-day mor- brinolysis within maximum delays rec- tality, a statistically nonsignificant increase in 1-year mortality, and significantly in- ommendedininternationalguidelines(90 creased risk of the composite of mortality or readmission for acute myocardial infarc- minutes for PPCI and 30 minutes for tion or heart failure at 1 year. 1,2 fibrinolysis). In these registries, shorter JAMA. 2010;303(21):2148-2155 www.jama.com treatment delays are associated with bet- 5,8-10 teroutcomes andresultsofthe2treat- low-up, frequent exclusion of patients ments of important covariates).7,8,10,13,14 11,12 ments tend to be similar. transferred for PPCI, and residual con- An assessment of bias within a large pa- However, registry data also have limi- founding (lack of detailed measure- tient registry found that a substantial pro- tations, including selection bias, infor- mation bias (noninclusion of patients re- Author Affiliations: Agence d’e´ valuation des technolo- Que´ bec City, Canada (Drs Rodes-Cabau and Bogaty). ferred for PPCI but not receiving it), gies et des modes d’interventions en sante´ (Drs Lam- Corresponding Author: Laurie Lambert, PhD, Cardi- bert and Bogaty and Mr Brown), Jewish General Hos- ology Evaluation Unit, Agence d’e´ valuation des tech- incomplete and inappropriately short fol- pital, McGill University/Urgences-sante´ (Dr Segal), and nologies et des modes d’interventions en sante´ (Que- McGill University Health Center, McGill University (Dr bec Healthcare Assessment Agency), 2021 Union Ave, Brophy), Montreal, Que´ bec, Canada; and Institut uni- Montreal, QC H3A 2S9, Canada (laurie.lambert See also pp 2156 and 2188. versitaire de cardiologie et pneumologie de Que´ bec, @aetmis.gouv.qc.ca). 2148 JAMA, June 2, 2010—Vol 303, No. 21 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 TIMELINESS OF THERAPY FOR ST-ELEVATION MI portion of eligible patients were not en- and followed a standardized data collec- cluded more than once during the ob- rolled and that these patients received tion process to abstract all information servation period, only the first event was poorer-quality care and had 3-fold higher directly from medical charts and enter retained in the analysis. in-hospital mortality than enrolled pa- data onto a secure, centralized Web site tients.13,14 Finally, registries based on with automatic encryption. At the Variables and Outcomes voluntary participation of institutions completion of data entry, date-time val- Clinical factors included age, sex, earli- usually provide information from well- ues were independently validated by se- est in-hospital measure of systolic blood performing, motivated academic and nior medical librarians in a representa- pressure, heart rate at first in-hospital research-oriented centers but tend to tive 10% sample and concordance was ECG, and symptom duration. A TIMI in- miss an important proportion of pa- very high (median difference for door to dex was calculated for each patient: tients in the larger real-world setting. reperfusion therapy=0 min [interquar- (heart rateϫ[age/10]2)/systolic blood To address these issues, the Agence tile range {IQR}, 0-0]).15 pressure.16 The TIMI index was used in d’e´valuation des techniques et modes Study eligibility was assessed via an al- statistical analyses rather than the 3 fac- d’interventions en sante´, a government- gorithm in all patients with appropriate tors individually because it has been vali- supported but independent health care presenting symptoms, a final diagnosis dated as a powerful predictor of mortal- evaluation agency in Quebec, Canada, re- ofAMI(InternationalClassificationofDis- ity in STEMI patients and improved the cently undertook a systematic province- eases,NinthRevisioncode410),andahos- statistical power of the multivariate wide evaluation of STEMI care in Que- pital discharge date between October 1, model.16 Anterior STEMI and left bundle bec (population, 7.8 million). The 2006,andMarch31,2007.Patientswhose branch block were centrally identified objectives were to obtain a contempo- AMIoccurredaftertheirinitialemergency based on the admission ECG. rary portrait of reperfusion treatments department presentation were excluded. Treatment time was calculated from and their delays across Quebec and to de- ForeachpotentialSTEMIpatient,thefirst patient arrival at the first hospital (door) termine whether STEMI reperfusion electrocardiogram (ECG) taken after ar- to either start of fibrinolysis (needle) or treatment outside of the guideline- rival at the emergency department was first dilation (balloon). To ascertain pa- recommended delays is associated with sent to the coordinating center, where it tient comorbidities, the recorded princi- poorer outcomes than treatment within was interpreted by 2 cardiologists and an pal diagnosis as well as the 15 secondary recommended delays. emergency physician. Patients included diagnosesofallhospitaladmissionsinthe in the evaluation had to have 1 of the fol- 5 years preceding the date of admission METHODS lowing features: (1) received fibrinoly- for the index STEMI were identified in The evaluation covered a 6-month period sis in the 4 hours following triage at the Quebec’s administrative hospital dis- (October 1, 2006, to March 31, 2007) and firstemergencydepartment;(2)weresent charge database. We included diagnoses included all acute care Quebec hospitals to a catheterization laboratory in the 4 in the index STEMI admission only for (n=80) that treated at least 30 acute myo- hours following triage at the first emer- comorbidities considered to be chronic cardial infarctions (AMIs) in the preced- gency department and had mention of to avoid confusing an index admission ing year. These 80 hospitals treat more STEMI in the medical chart or, if not, evi- complication with a comorbidity. than 95% of all AMIs occurring in Que- denceofSTEMIonthefirstECGvalidated The primary end points were death at bec and are distributed across 15 of Que- at the coordinating
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