Comparison of calcium-channel blockers for long-term clinical outcomes in patients with vasospastic angina

Abstract

Background/Aims: Calcium channel blockers (CCBs) are the most widely prescribed medication for patients with vasospastic angina (VA). However, few studies have compared the prognosis of VA patients who are prescribed different CCBs. Methods: We enrolled 2,960 patients who received provocation test prospectively in 11 university hospitals in Korea. We divided 1,586 patients received four major CCBs into two groups: a first generation CCB (diltiazem and nifedipine) group and a second generation CCB (amlodipine and benidipine) group. Primary outcome was time to events of composite of death from any cause, acute coronary syndrome (ACS) and symptomatic arrhythmia during 3-year follow-up. We also compared the effect of each CCB on the control of angina symptoms. Results: There was no difference of the primary outcome among the two groups with a cumulative incidence rate of 5.4%, 2.9%, and a person-month incidence rate of 2.33 and 1.26, respectively (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.25 to 1.17; p = 0.120, as reference with the 1st generation CCBs). The incidence of ACS was significantly lower in 2nd generation CCBs group with a person-month incidence rate of 1.66 vs. 0.35 (HR, 0.22; 95% CI, 0.05 to 0.89; p = 0.034). Use of benidipine showed a significant better control of angina symptom compared with diltiazem for 3-years (odds ratio, 0.17; 95% CI, 0.09 to 0.32; p < 0.0001 at 3rd year). Conclusions: The first and second generation CCB groups did not differ in terms of composite outcome occurrence. However, the ACS incidence rate was significantly lower in the users of the 2nd generation CCBs.

Current Evidence on Long-Term Prognostic Factors in Vasospastic Angina

“…Another study found that CCB did not affect the prognosis of patients with VSA with multi-vessel CAD but was a significant prognostic factor in patients without multi-vessel CAD [ 13 ]. A recent Korean study showed that the type of CCB (first generation (diltiazem and nifedipine) vs. second generation (amlodipine and benidipine) CCBs) did not affect the long-term prognosis of VSA patients [ 62 ]. In addition, adherence to medication is an important prognostic factor in VSA.…”

Contemporary pharmacological treatment strategies for patients with angina and unobstructed coronary arteries (ANOCA) due to coronary microvascular dysfunction

“…Benidipine was initially licensed for use in Japan and selected Southeast Asian countries and later in Turkey. A meta-analysis that compared the prognostic effects of four CCBs (amlodipine, nifedipine, diltiazem, and benidipine) showed a significant superiority of benidipine regarding the occurrence of major adverse cardiovascular events in Japanese patients with a history of vasospastic angina attacks [38] . In addition, use of benidipine showed significantly better control of angina symptoms compared with diltiazem [39] .…”

A new perspective on calcium channel blockers in vasospastic angina

“…In particular, there are insufficient data on whether the new generation CCBs are as effective as the first generation CCBs [8]. Thus, the research results presented by Kim et al [6] deserve clinical attention. The authors of this study investigated 1,586 patients with significant or intermediate vasospasm using an ergonovine provocation test, and demonstrated that the occurrence of composite events including death, acute coronary syndrome (ACS), and symptomatic arrhythmia during a 3-year clinical follow-up did not differ between patients treated with first (nifedipine and diltiazem) and second (amlodipine and benidipine) generation CCBs.…”

“…Newer CCBs such as amlodipine and benidipine were developed in the 1990s [3]. Because diltiazem has been available longer, there are more data on its use, and diltiazem is the most commonly prescribed CCB for VA patients in Korea [6] and Japan [7]. Although the efficacy of newer CCBs such as amlodipine and benidipine for the prevention of VA has been proven in several studies [3,8,9], their use in VA patients remains less than that of diltiazem.…”

“…It may even be necessary to use amlodipine or benidipine as the primary treatment option for some VA patients. However, it is important to recognize a limitation of the Kim et al's [6] study; a relatively small number of patients taking second generation CCBs was enrolled. Further study of a larger number of patients taking second generation CCBs is warranted to clarify the role of second generation CCBs in the treatment of VA patients.…”