Clinical outcomes of low-dose aspirin administration in patients with variant angina pectoris

Abstract

Variant angina pectoris (VAP) is different to classical atherosclerotic AP in terms of etiology, treatment, and prognosis [1,2]. However, the role of acetylsalicylic acid (aspirin), indispensable for management of AP and acute coronary syndrome associated with atherosclerotic plaque, is unclear in patients with VAP and large dose (325 mg daily) of aspirin can aggravate coronary artery vasospasm in patients with VAP [2,3]. However, there is no current available data regarding clinical outcomes in patients with VAP prescribed with low dose aspirin. We investigated one-year clinical outcomes of low dose aspirin usage in patients with VAP diagnosed by ergonovine provocation test. Between June 2000 and May 2009, a total of 424 patients visited Chonnam National University Hospital was analyzed and all patients had positive results on intracoronary ergonovine provocation test. Patients were divided into two groups by prescription of aspirin as a discharge medication: aspirin group (n=202, 54.1± 11.1 years, 71.8% male) and non-aspirin group (n=222, 51.6± 10.6 years, 62.2% male). Student's t-test, chi-square test, and Kaplan–Meier method were performed using SPSS for Window 17.0. Protocol for ergonovine provocation test was similar to other Korean studies regarding VAP [4,5]. Primary study outcomes were composite one-year readmission rate associated with recurrent angina, cardiac death, and percutaneous coronary intervention (PCI) during one-year follow-up period. Aspirin group was more older (54.1±11.1 vs. 51.6±10.6 years, p=0.018) and had more male patients (71.8% vs. 62.2%, p=0.039). There were more patients presented with ST-elevation myocardial infarction at initial hospital visit in aspirin group (9.4 vs. 2.8%, p= 0.005) and unstable AP or VAP in non-aspirin group (71.2 vs. 80.1%, p=0.037). Other baseline characteristics and laboratory findings were similar between two groups. On baseline coronary angiogram, insignificant coronary artery stenosis (defined as less than 70% of stenosis in one or more epicardial coronary arteries) was more frequently observed in aspirin group (48.0 vs. 27.0%, pb0.001). However, diffuse coronary artery spasm provoked by intracoronary ergonovine test was more frequently observed in non-aspirin group (29.2 vs. 43.7%, p=0.002). At discharge, all patients received at least one or more calcium-channel blocker at maximally tolerable dose with or without nitrate. A total of 387 patients (91.3%) completed one-year follow-up. Occurrence of composite events was similar between two groups (21.9 vs. 21.0%, p=0.901) including readmission rate due to recurrent angina (19.3 vs. 19.0%, p=1.000), cardiac death (1.1 vs. 1.0%, p=1.000), and PCI 0(1.6 vs. 1.0%, p= 0.676) (Table 1). In subgroup analysis by presence of insignificant coronary artery stenosis, one-year clinical outcomes were not different. Fig. 1A showed one-year readmission-free survival associated with recurrent angina between two groups and there was no difference (log-rank p=0.959). Similar results were observed in patients with or without insignificant coronary artery stenosis in survival analysis (Fig. 1B and C). Initial point of our present study was that aspirin has efficacy in improvement of clinical outcomes in concomitant VAP and insignificant coronary artery stenosis. Although prior studies have shown that significant coronary artery stenosis is associated with a worse prognosis in patients with VAP, there is a report that variant angina with mild fixed coronary stenosis has a good prognosis during long-term follow-up [6,7]. On the basis of study results, low-dose aspirin combinationwith calcium-channel blocker should be considered in patients with concomitant VAP and significant coronary artery stenosis. In our current study, low-dose aspirin was prescribed in nearly 50% of study patients by decision of cardiologists. Because there is no definitive evidence of high prescription rate, we evaluated independent predictors of aspirin administration in all patients. Only an insignificant coronary artery stenosis on baseline coronary angiogram was a predictor of aspirin prescription at discharge (odd ratio 2.50, 95% confidence interval 1.59 to 3.75, pb0.001). Although ST-segment elevationmyocardial infarction at initial presentation was potentially associated with aspirin usage (odd ratio 2.54, 95% confidence interval 0.95 to 6.78, p=0.063), itwasmaybe sequential prescription from initial hospital visit. Diffuse coronary