hpic.gif (2871 bytes)
Volume 4, Number 2: February 2001

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

Anti-restenosis Trials

Different vascular risk factor profiles in ischemic stroke subtypes: a study from the "Sagrat Cor Hospital of Barcelona Stroke Registry"


Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia

Reference: J Cardiovasc Pharmacol Ther 2000;5(3):183-91.

BACKGROUND: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. 

PATIENTS AND METHODS: Thirteen patients with chronic atrial fibrillation associated with bradycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. 

RESULTS: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 +/- 0.8 weeks (mean +/- SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was significantly improved and the plasma atrial natriuretic polypeptide level was significantly decreased after the initiation of cilostazol treatment. 

CONCLUSION: Cilostazol improves the slow HR episodes associated with chronic atrial fibrillation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.


Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

Reference: Am Heart J 2001;141(1):124-130.

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. 

METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. 

RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58 +/- 0.52 mm vs 1.09 +/- 0.65 mm, P <.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs 33%, P =.044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). 

CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.


Anti-restenosis Trials.

Reference: Current Interventional Cardiology Reports 2000;2(4):326-331.

The high frequency of restenosis after percutaneous coronary angioplasty is still a major clinical problem. It occurs in 30% to 60% of patients and limits the long-term success of angioplasty. Many clinical trials have been conducted to resolve this problem, using a wide range of pharmacologic agents such as antiplatelet agents, anticoagulation drugs, lipid-lowering drugs, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, and antiproliferative drugs. Thus far, no effective drug has been reported, with the exception of probucol, which unfortunately is not approved by the US Food and Drug Administration because it prolongs the QT time, and possibly trapidil and cilostazol, two agents that are currently being tested in larger trials. Stent implantation has significantly reduced the frequency of restenosis in patients with 1) short lesions in large coronary arteries, (> 3.0 mm), 2) native coronary restenosis lesions, 3) venous bypass graft obstructions, 4) chronic total occlusions, and 5) acute myocardial infarction in patients referred for primary percutaneous intervention. A significant problem is the occurrence of in-stent restenosis because it is associated with a high recurrence of restenosis, after repeat coronary intervention irrespective of the technique or device used. Brachytherapy may limit this problem. The high restenosis rate occurring in long lesions and in small vessels still remains an unresolved issue.


Different vascular risk factor profiles in ischemic stroke subtypes: a study from the "Sagrat Cor Hospital of Barcelona Stroke Registry"

Reference: Acta Neurol Scand 2000;102(4):264-70.

OBJECTIVES: To characterize the vascular risk factor profiles in different subtypes of ischemic stroke. 

MATERIAL AND METHODS: The study population consisted of 1473 consecutive ischemic stroke patients collected in a prospective stroke registry. The prevalence of vascular risk factors in each stroke subtype was analyzed independently and in comparison with other subtypes of stroke pooled together by means of univariate analysis and logistic regression models. 

RESULTS: Hypertension was present in 52% of patients followed by atrial fibrillation in 27% and diabetes in 20%. The pattern of risk factors associated with atherothrombotic stroke included chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 2.63), hypertension (OR = 2.55), diabetes (OR = 2.26), transient ischemic attack (OR = 1.61), and age (OR = 1.03). Previous cerebral hemorrhage (OR = 4.72), hypertension (OR = 4.29), obesity (OR = 2.45), and diabetes (OR = 1.73) were strong predictors of lacunar stroke. In the case of cardioembolic stroke, atrial fibrillation (OR = 22.24), valvular heart disease (OR = 10.97), and female gender (OR = 1.66) occurred more frequently among patients with this stroke subtype than among the other stroke subtypes combined. 

CONCLUSION: Different potentially modifiable vascular risk factor profiles were identified for each subtype of ischemic stroke, particularly COPD in the case of atherothrombotic stroke and previous cerebral hemorrhage and hypertension in the case of lacunar infarction.