Korean Circulation Journal 대한심장학회지 순환기 Kim HL, et al. Korean Circ J. 2022 Feb;52(2):93-109. https://doi.org/10.4070/kcj.2021.0328

Anti-platelet agents are commonly used in vasospastic angina (VA) patients with comorbidity like coronary artery disease. However, long-term clinical outcomes in the use of aspirin, clopidogrel or the two agents together have rarely been investigated in VA patients. In a prospective study, we enrolled 2960 patients who received coronary angiography and ergonovine provocation test at 11 university hospitals in Korea. Among them, 1838 patients were diagnosed either with definite (n = 680) or intermediate (n = 1212) VA, using the criteria of chest pain, ECG changes and ergonovine provocation test results. They were analyzed according to their use of aspirin, clopidogrel or both, or no anti-platelet agent at all. The primary outcome was time to composite events of death from any cause, acute coronary syndrome (ACS) and symptomatic arrhythmia during a 3-year follow-up. A primary composite outcome was significantly more common in the aspirin plus clopidogrel group, at 10.8% (14/130), as compared with the non-antiplatelet group, at 4.4% (44/1011), (hazard ratio [HR] 2.41, 95% confidence interval [CI], 1.32–4.40, p = 0.004). With regard to the person-time event rate, similar results were shown, with the highest rate in the aspirin plus clopidogrel user at 4.72/1000 person months (95% CI, 2.79–7.96, log-rank test for primary outcome p = 0.016). The person-time event of the ACS rate was also highest in that group, at 2.81 (95% CI, 1.46–5.40, log-rank test for ACS p = 0.116). Kaplan-Meier survival analysis demonstrated poor prognosis in primary outcomes and ACS in aspirin plus clopidogrel users (log-rank test, p = 0.005 and p = 0.0392, respectively). Cox-proportional hazard regression analysis, adjusting for age, sex, history of coronary heart disease, hypertension, diabetes, presence or not of definite spasm, use of calcium channel blocker, demonstrated that the use of aspirin plus clopidogrel is an independent risk for the primary outcome (HR 2.01, CI: 1.07–3.81, p = 0.031). The aspirin-alone group had a similar primary and individual event rate compared to the no-antiplatelet agent group (HR 0.96, CI, 0.59–1.55, p = 0.872). Smokers using aspirin plus clopidogrel had poorer outcomes than non-smokers, with HR 6.36 (CI 2.31–17.54, p = 0.045 for interaction). In conclusion, among VA patients, aspirin plus clopidogrel use is associated with a poor clinical outcome at 3 years, especially in ACS. Aspirin alone appears to be safe for use in those patients.

Lee JY, et al. Korean Circ J. 2016 Sep;48:e122. https://doi.org/10.4070/kcj.2018.0115

Obesity is associated with a high risk of morbidity and mortality in the general population and is a major independent risk factor for cardiovascular disease. We sought to evaluate the effect of overweight/obesity on clinical outcomes of patients with vasospastic angina (VA) at 1-year follow-up. The VA-KOREA (Vasospastic Angina in Korea) registry was a cohort of 11 centers from 2010 to 2015. The primary endpoint was a composite of cardiac death (CD), new-onset arrhythmia, and acute coronary syndrome (ACS). Using the body mass index (BMI) cut-off for Asians, 517 patients with definite VA were divided into either an overweight/obese (BMI ≥ 23 kg/m²) group (n = 378) or a normal weight (BMI 18.5–22.9 kg/m²) group (n = 139). The overweight/obese group showed a significantly lower rate of the primary endpoint composite (2.4% vs 7.9%, p = 0.004) and ACS (0.8% vs 4.3%, p = 0.007) than the normal weight group in the crude population. Similarly, in propensity-score matched analysis, the overweight/obese group showed a significantly lower rate of the primary endpoint composite (2.3% vs 8.4%, p = 0.006) and ACS (1.1% vs 4.6%, p = 0.035) than the normal weight group. However, there were no significant differences in CD and new-onset arrhythmia between the two groups in both the crude and propensity-score matched population. Independent predictors of the primary endpoint were overweight/obesity and dyslipidemia. In patients with VA, the overweight/obese group was associated with a favorable 1-year primary endpoint and the difference was mainly driven by the lower rate of ACS compared with the normal weight group.

Vasospastic angina (VA) is a functional disease caused by the alteration of vasomotor tone. We investigated the association of hyperthyroidism with the development and prognosis of VA. Study data were obtained from a prospective multicenter registry that included patients who had symptoms suggestive of VA. Coronary angiography and an ergonovine provocation test were performed, and patients were classified into a VA and a non-VA group. Among 1239 patients with suspected VA, 831 patients were classified in the VA group. Hyperthyroidism was more common in the VA group than in the non-VA group (10.0% vs. 3.7%, p < 0.001). After adjusting for confounding factors, hyperthyroidism was independently associated with a 3.27-fold increased risk of VA. Especially in women, hyperthyroidism was associated with a 4.38-fold higher risk of VA. All-cause death rates did not differ according to the presence or absence of hyperthyroidism. Hyperthyroidism is independently associated with the occurrence of VA especially in women but did not affect the total death in VA patients. Clinicians need to be aware of the role of thyroid function in patients with suspected VA.

Vasospastic angina (VA) is a functional disease of the coronary artery and occurs in an angiographically normal coronary artery. However, it may also occur with coronary artery stenosis. We investigated the effect of coronary artery stenosis on clinical outcomes in VA patients. Study data were obtained from a prospective multicenter registry that included patients who had symptoms of VA. Patients were classified into two groups according to presence of significant coronary artery stenosis. Among 1920 patients with VA, 189 patients were classified in the “significant stenosis” group. The one-year composite clinical events rate was significantly higher in the significant stenosis group than in the “no significant stenosis” group (5.8% vs. 1.4%, respectively; p < 0.001). Additionally, the prevalence of ACS was significantly greater in the “significant stenosis” group (4.8% vs. 0.9%, respectively; p < 0.001). After propensity score matching, the adverse effects of significant stenosis remained. In addition, significant stenosis was independently associated with a 6.67-fold increased risk of ACS in VA patients. In conclusion, significant coronary artery stenosis can increase the adverse clinical outcomes in VA patients at long-term follow-up. Clinicians should manage traditional risk factors associated with atherosclerosis and control vasospasm as well as reduce the burden of atherosclerosis.