Limited data exist regarding the management of patients with acute coronary syndrome (ACS) in high-income countries compared with low/middle-income countries. We aimed to compare in-hospital trends of revascularization and prescription of medications at discharge in patients with ACS from high-income (Canada and United States) and low/middle-income (India, Iran, Pakistan, and Tunisia) countries. Data from a double-blind, placebo-controlled, randomized trial investigating the effect of bupropion on smoking cessation in patients after an enzyme-positive ACS was used for our study. A total of 392 patients, 265 and 127 from high-income and from low/middle-income countries, respectively, were enrolled. Patients from high-income countries were older, and were more likely to have diagnosed hypertension and dyslipidemia. During the index hospitalization, patients from high-income countries were more likely to be treated by percutaneous coronary intervention (odds ratio [OR] 19.7, 95% confidence interval [CI] 10.5 to 37.0). Patients with ST elevation myocardial infarction from high-income countries were more often treated by primary percutaneous coronary intervention (OR 16.3, 95% CI 6.3 to 42.3) in contrast with thrombolytic therapy (OR 0.24, 95% CI 0.14 to 0.41). Patients from high-income countries were also more likely to receive evidence-based medications at discharge (OR 2.32, 95% CI 1.19 to 4.52, a composite of aspirin, clopidogrel, and statin). In conclusion, patients with ACS in low/middle-income countries were less likely to be revascularized and to receive evidence-based medications at discharge. Further studies are needed to understand the underutilization of procedures and evidence-based medications in low/middle-income countries.
The Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome (ZESCA) Trial is a multicenter, double-blind, placebo-controlled, randomized trial that examined the effect of bupropion on smoking cessation rates at 1 year after an enzyme-positive acute coronary syndrome (ACS). The trial was carried out in 6 countries across 3 continents, representing different regions and ethnic groups in high- and low/middle-income countries. To assess the current trends in the in-hospital management of patients with ACS, and more specifically to describe the differences between high-income and low/middle-income countries, patient-level data from the ZESCA trial were used for our present study.
Methods
Patients were enrolled in 38 centers from 6 countries in Asia (India, Iran, and Pakistan), North Africa (Tunisia), and North America (Canada and United States). These countries were further classified as low-, middle-, or high-income countries based on the World Bank Classification, and low- and middle-income countries were further grouped for the analyses. India and Pakistan were classified as low-income, Iran and Tunisia as higher middle-income, and Canada and United States as high-income countries. Centers with established research infrastructures were selected for participation in the study. Patients admitted to an intensive cardiac care unit or equivalent cardiac ward were screened. Eligible patients included current smokers (smoked ≥10 cigarettes/day over the past year) who had enzyme-positive ACS, validated by troponin or creatine kinase-MB, characteristic symptoms of ACS, and electrocardiographic changes indicative of a new myocardial infarction (MI). Subjects were ineligible if they had a medical condition with a life expectancy of ≤1 year; renal impairment with creatinine levels ≥2 times the upper limit of normal; diagnosis of severe hepatic disease or hepatic impairment with hepatic enzymes ≥2 times the upper limit of normal; history of seizure disorder; current seizure disorder; current diagnosis of major depression; history of suicidal events or family history of suicide; history of excessive alcohol consumption; history of illegal drug use in the past year; current use of any medical therapy for smoking cessation; and pregnant or lactating women. All eligible patients provided written informed consent before randomization. Patients were enrolled from December 27, 2005 to May 29, 2009. The research ethics boards at all participating centers approved the protocol. The study complied with the Good Clinical Practice standards and the Declaration of Helsinki. An independent data safety monitoring board and the steering committee supervised the trial.
Data were collected by chart review and structured questionnaires. Baseline demographic characteristics, history of cardiovascular disease, established cardiovascular risk factors, and relevant clinical data were collected for subjects included in the study. In-hospital data were prospectively collected. Patients received bupropion or placebo in-hospital for 9 weeks and motivational support at baseline and follow-up visits. The attending physician determined the course of treatment for the patient’s cardiac event.
Categorical variables are expressed as proportions. Continuous variables are summarized as means ± SD or medians with their respective interquartile ranges. Between-group comparisons for continuous variables were analyzed as mean differences with corresponding 95% confidence intervals (CIs). Comparisons between groups for proportions were expressed as odds ratios with corresponding 95% CIs. Variables associated with revascularization at index admission and adherence to evidence-based medications at discharge were assessed by multivariate regression analyses. Variables were selected based on clinical judgment and the decision to keep them in the model was determined by Bayesian information criterion and Bayesian model averaging. Data were analyzed using SPSS (version 16.0; SPSS Inc., Chicago, Illinois).
Results
Of the 392 patients enrolled, 127 and 265 were from high-income and low/middle-income countries, respectively ( Table 1 ). Of these patients, 64% and 36% were diagnosed with ST elevation myocardial infarction (STEMI) and non-STEMI, respectively. Patients were primarily men (83.5%) and the mean age was 53.9 ± 10.3 years. The mean age was similar among men and women (53.8 ± 10.3 vs 54.6 ± 10.7 years; mean difference −0.78 years, 95% CI −2.0 to 3.6). Patients from low/middle-income countries were younger, had lower body mass indexes, and were less likely to have been diagnosed with dyslipidemia and hypertension. No clinically important differences were observed with respect to diabetes mellitus, history of MI, or stroke. The number of cigarettes smoked per day at index admission was higher in patients from low/middle-income countries. However, these patients were less likely to report living with other smokers at home.
| Variable | High-Income Countries (n = 265) | Low/Middle-Income Countries (n = 127) | Mean Difference | Odds Ratio | 95% CI |
|---|---|---|---|---|---|
| Age (yrs) | 55.3 ± 9.9 | 50.9 ± 10.6 | 4.5 | — | 2.3–6.6 |
| Men | 76.0 | 99.2 | — | 0.0 | 0.0–0.2 |
| STEMI at admission | 57.1 | 81.0 | — | 0.3 | 0.2–0.5 |
| Diabetes mellitus | 16.9 | 17.5 | — | 1.0 | 0.6–1.7 |
| Dyslipidemia ∗ | 54.8 | 38.1 | — | 2.0 | 1.3–3.0 |
| Hypertension † | 49.0 | 19.0 | — | 4.1 | 2.5–6.8 |
| Body mass index (kg/m 2 ) | 28.5 ± 5.3 | 25.5 ± 3.9 | 3.0 | — | 1.9–4.0 |
| Previous MI | 19.9 | 23.0 | — | 0.8 | 0.5–1.4 |
| Previous PCI | 13.0 | 4.8 | — | 3.0 | 1.2–7.3 |
| Previous coronary artery bypass graft surgery | 4.2 | 0.0 | — | — | — |
| Previous stroke | 1.9 | 1.6 | — | 1.2 | 0.2–6.3 |
| No. of cigarettes/day | 22.5 ± 10.3 | 24.7 ± 11.1 | 2.2 | — | −0.6 to 4.5 |
| No. of years smoking | 35.2 ± 12.3 | 27.8 ± 11.2 | 7.5 | — | 4.9–10.0 |
| Other smokers at home | 46.2 | 15.1 | — | 4.8 | 2.8–8.3 |
∗ Dyslipidemia: a lipoprotein metabolism disorder characterized by elevated levels of plasma cholesterol, low-density lipoproteins and/or triglycerides, or decreased levels of high-density lipoproteins.
† Hypertension: persistently high systemic arterial blood pressure. Based on several readings defined as systolic pressure >140 mm Hg or when diastolic pressure is ≥90 mm Hg.
The median length of hospital stay was 5.7 ± 6.1 days and did not differ between the 2 groups ( Table 2 ). Diagnostic coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery were done in 66.6%, 50.1%, and 6.5% of all patients, respectively. Patients from low/middle-income countries were less likely to have diagnostic coronary angiography and were less likely to be treated by PCI at index admission. No patients from low/middle-income countries were treated by coronary artery bypass graft surgery compared with 9.6% of patients from high-income countries. Of the 251 patients with STEMI, 81.7% were treated with reperfusion therapy (either fibrinolysis or primary PCI) with no differences between the 2 groups. However, relative to those in high-income countries, patients from low/middle-income countries were less often treated by primary PCI (4.9% vs 45.6%, odds ratio [OR] 0.06, 95% CI 0.02 to 0.16) than with thrombolytic therapy (72.5% vs 38.9%, OR 4.2, 95% CI 2.4 to 7.1).
| Variable | High-Income Countries | Low/Middle-Income Countries | Mean Difference | OR | 95% CI |
|---|---|---|---|---|---|
| All patients | (n = 265) | (n = 127) | |||
| Length of stay (days) | 6.0 ± 6.8 | 5.1 ± 4.5 | 0.93 | — | −0.4 to 2.3 |
| Diagnostic angiography | 92.0 | 16.7 | — | 57.1 | 29.9–109.1 |
| Any PCI | 69.3 | 10.3 | — | 19.7 | 10.5–37.0 |
| Coronary artery bypass graft surgery | 9.6 | 0.0 | — | — | — |
| Patients with STEMI | (n = 149) | (n = 102) | |||
| Length of stay (days) | 5.1 ± 5.1 | 5.3 ± 4.8 | 0.22 | — | −1.1 to 1.5 |
| Diagnostic angiography | 91.3 | 15.7 | — | 56.2 | 25.8–122.7 |
| Reperfusion therapy | 84.6 | 77.5 | — | 1.6 | 0.8–3.0 |
| Thrombolysis | 38.9 | 72.55 | — | 0.24 | 0.1–0.4 |
| Primary PCI | 45.6 | 4.9 | — | 16.3 | 6.3–42.3 |
| CABG | 5.4 | 0.0 | — | — | — |
Patients from low/middle-income countries were less likely to receive evidence-based medications such as clopidogrel and statins ( Table 3 ). The low rate of clopidogrel prescription at discharge in low/middle-income countries is consistent with the rates of PCI. In contrast, angiotensin-converting enzyme inhibitors were more often prescribed to patients from low/middle-income countries. No clinically important differences were found for prescription of aspirin or β-blockers at discharge. In patients treated by either PCI or medical therapy, living in a high-income country and in-hospital PCI were found to be independent predictors of adherence to a composite of evidence-based medications (aspirin, statins, clopidogrel, and β-blockers) at discharge ( Table 4 ).
| Variable | High-Income Countries (n = 265) | Low/Middle-Income Countries (n = 127) | Odds Ratio | 95% CI |
|---|---|---|---|---|
| Aspirin | 96.5 | 97.6 | 0.7 | 0.2–2.5 |
| Angiotensin-converting enzyme inhibitors | 64.2 | 87.2 | 0.3 | 0.2–0.5 |
| Angiotensin receptor blockers | 5.8 | 4.0 | 1.5 | 0.5–4.2 |
| β-Blockers | 88.7 | 82.4 | 1.7 | 0.9–3.1 |
| Clopidogrel | 82.1 | 33.6 | 9.1 | 5.6–14.8 |
| Statins | 90.3 | 76.8 | 2.8 | 1.6–5.0 |
| Variable | Odds Ratio (95% CI) |
|---|---|
| Composite of aspirin, clopidogrel, and statins (n = 357) ∗ | |
| Any PCI/conservative ∗ | 17.1 (8.6–33.9) |
| High-income/low/middle-income country | 2.4 (1.2–4.4) |
| Composite of aspirin, clopidogrel, statins, and β-blockers (n = 358) ∗ | |
| Any PCI/conservative ∗ | 7.2 (4.0–13.0) |
| High-income/low/middle-income country | 3.1 (1.7–5.7) |
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