Type 3 Phosphodiesterase Inhibitors May Be Protective Against Cerebrovascular Events in Patients with Claudication

William M. Stone, Bart M Demaerschalk, Richard J. Fowl, Samuel R. Money

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: The risk of cerebrovascular events in patients with mild to moderate peripheral vascular disease is significant. Cilostazol is a phosphodiesterase type 3 (PDE3) inhibitor that is effective in the treatment of symptoms of peripheral arterial occlusive disease. The method of action includes antithrombotic, vasodilatory, and antiproliferative effects. Methods: The Cilostazol: A Study in Long-Term Effects (CASTLE) trial was a prospective randomized double-blinded trial to establish the safety of this PDE3 inhibitor use in 1435 patients with mild to moderate peripheral arterial occlusive disease. A post hoc analysis of the CASTLE trial was undertaken to evaluate cilostazol use on cerebrovascular events. Blinded adjudication of all cerebrovascular events (stroke, transient ischemic attack, and carotid revascularization) in this trial was performed. Kaplan-Meier analysis was used for statistical evaluation. Results: The overall rate of cerebrovascular events was 4.6% (67 of 1435 patients) with a mean follow-up of 515 days. Ischemic vascular events were more common (2.5%) than hemorrhagic events (0.3%; P < .05). The placebo group demonstrated a greater risk for events (6.1%; 43 of 718 patients) versus the cilostazol treated group (3.2%; 24 of 717 patients; P < .05). Cerebrovascular risk factors were similar in both groups. Conclusion: The risk of cerebrovascular events in patients with mild to moderate peripheral arterial occlusive disease is 4.6% with a mean follow-up of 515 days. Treatment with PDE3 inhibitors may reduce this risk. Further evaluation of the use of PDE3 inhibitors for prevention of cerebrovascular events should be considered.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalJournal of Stroke and Cerebrovascular Diseases
Volume17
Issue number3
DOIs
StatePublished - May 2008

Fingerprint

Phosphodiesterase 3 Inhibitors
Arterial Occlusive Diseases
Peripheral Arterial Disease
Peripheral Vascular Diseases
Transient Ischemic Attack
Kaplan-Meier Estimate
Blood Vessels
Stroke
Placebos
cilostazol
Safety
Therapeutics

Keywords

  • cerebrovascular accident
  • claudication
  • peripheral vascular disease
  • Prevention

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Health Professions(all)

Cite this

Type 3 Phosphodiesterase Inhibitors May Be Protective Against Cerebrovascular Events in Patients with Claudication. / Stone, William M.; Demaerschalk, Bart M; Fowl, Richard J.; Money, Samuel R.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 17, No. 3, 05.2008, p. 129-133.

Research output: Contribution to journalArticle

@article{b4352f1990a24c8792c01f98887b26f5,
title = "Type 3 Phosphodiesterase Inhibitors May Be Protective Against Cerebrovascular Events in Patients with Claudication",
abstract = "Objective: The risk of cerebrovascular events in patients with mild to moderate peripheral vascular disease is significant. Cilostazol is a phosphodiesterase type 3 (PDE3) inhibitor that is effective in the treatment of symptoms of peripheral arterial occlusive disease. The method of action includes antithrombotic, vasodilatory, and antiproliferative effects. Methods: The Cilostazol: A Study in Long-Term Effects (CASTLE) trial was a prospective randomized double-blinded trial to establish the safety of this PDE3 inhibitor use in 1435 patients with mild to moderate peripheral arterial occlusive disease. A post hoc analysis of the CASTLE trial was undertaken to evaluate cilostazol use on cerebrovascular events. Blinded adjudication of all cerebrovascular events (stroke, transient ischemic attack, and carotid revascularization) in this trial was performed. Kaplan-Meier analysis was used for statistical evaluation. Results: The overall rate of cerebrovascular events was 4.6{\%} (67 of 1435 patients) with a mean follow-up of 515 days. Ischemic vascular events were more common (2.5{\%}) than hemorrhagic events (0.3{\%}; P < .05). The placebo group demonstrated a greater risk for events (6.1{\%}; 43 of 718 patients) versus the cilostazol treated group (3.2{\%}; 24 of 717 patients; P < .05). Cerebrovascular risk factors were similar in both groups. Conclusion: The risk of cerebrovascular events in patients with mild to moderate peripheral arterial occlusive disease is 4.6{\%} with a mean follow-up of 515 days. Treatment with PDE3 inhibitors may reduce this risk. Further evaluation of the use of PDE3 inhibitors for prevention of cerebrovascular events should be considered.",
keywords = "cerebrovascular accident, claudication, peripheral vascular disease, Prevention",
author = "Stone, {William M.} and Demaerschalk, {Bart M} and Fowl, {Richard J.} and Money, {Samuel R.}",
year = "2008",
month = "5",
doi = "10.1016/j.jstrokecerebrovasdis.2007.12.005",
language = "English (US)",
volume = "17",
pages = "129--133",
journal = "Journal of Stroke and Cerebrovascular Diseases",
issn = "1052-3057",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Type 3 Phosphodiesterase Inhibitors May Be Protective Against Cerebrovascular Events in Patients with Claudication

AU - Stone, William M.

AU - Demaerschalk, Bart M

AU - Fowl, Richard J.

AU - Money, Samuel R.

PY - 2008/5

Y1 - 2008/5

N2 - Objective: The risk of cerebrovascular events in patients with mild to moderate peripheral vascular disease is significant. Cilostazol is a phosphodiesterase type 3 (PDE3) inhibitor that is effective in the treatment of symptoms of peripheral arterial occlusive disease. The method of action includes antithrombotic, vasodilatory, and antiproliferative effects. Methods: The Cilostazol: A Study in Long-Term Effects (CASTLE) trial was a prospective randomized double-blinded trial to establish the safety of this PDE3 inhibitor use in 1435 patients with mild to moderate peripheral arterial occlusive disease. A post hoc analysis of the CASTLE trial was undertaken to evaluate cilostazol use on cerebrovascular events. Blinded adjudication of all cerebrovascular events (stroke, transient ischemic attack, and carotid revascularization) in this trial was performed. Kaplan-Meier analysis was used for statistical evaluation. Results: The overall rate of cerebrovascular events was 4.6% (67 of 1435 patients) with a mean follow-up of 515 days. Ischemic vascular events were more common (2.5%) than hemorrhagic events (0.3%; P < .05). The placebo group demonstrated a greater risk for events (6.1%; 43 of 718 patients) versus the cilostazol treated group (3.2%; 24 of 717 patients; P < .05). Cerebrovascular risk factors were similar in both groups. Conclusion: The risk of cerebrovascular events in patients with mild to moderate peripheral arterial occlusive disease is 4.6% with a mean follow-up of 515 days. Treatment with PDE3 inhibitors may reduce this risk. Further evaluation of the use of PDE3 inhibitors for prevention of cerebrovascular events should be considered.

AB - Objective: The risk of cerebrovascular events in patients with mild to moderate peripheral vascular disease is significant. Cilostazol is a phosphodiesterase type 3 (PDE3) inhibitor that is effective in the treatment of symptoms of peripheral arterial occlusive disease. The method of action includes antithrombotic, vasodilatory, and antiproliferative effects. Methods: The Cilostazol: A Study in Long-Term Effects (CASTLE) trial was a prospective randomized double-blinded trial to establish the safety of this PDE3 inhibitor use in 1435 patients with mild to moderate peripheral arterial occlusive disease. A post hoc analysis of the CASTLE trial was undertaken to evaluate cilostazol use on cerebrovascular events. Blinded adjudication of all cerebrovascular events (stroke, transient ischemic attack, and carotid revascularization) in this trial was performed. Kaplan-Meier analysis was used for statistical evaluation. Results: The overall rate of cerebrovascular events was 4.6% (67 of 1435 patients) with a mean follow-up of 515 days. Ischemic vascular events were more common (2.5%) than hemorrhagic events (0.3%; P < .05). The placebo group demonstrated a greater risk for events (6.1%; 43 of 718 patients) versus the cilostazol treated group (3.2%; 24 of 717 patients; P < .05). Cerebrovascular risk factors were similar in both groups. Conclusion: The risk of cerebrovascular events in patients with mild to moderate peripheral arterial occlusive disease is 4.6% with a mean follow-up of 515 days. Treatment with PDE3 inhibitors may reduce this risk. Further evaluation of the use of PDE3 inhibitors for prevention of cerebrovascular events should be considered.

KW - cerebrovascular accident

KW - claudication

KW - peripheral vascular disease

KW - Prevention

UR - http://www.scopus.com/inward/record.url?scp=43049183212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43049183212&partnerID=8YFLogxK

U2 - 10.1016/j.jstrokecerebrovasdis.2007.12.005

DO - 10.1016/j.jstrokecerebrovasdis.2007.12.005

M3 - Article

C2 - 18436153

AN - SCOPUS:43049183212

VL - 17

SP - 129

EP - 133

JO - Journal of Stroke and Cerebrovascular Diseases

JF - Journal of Stroke and Cerebrovascular Diseases

SN - 1052-3057

IS - 3

ER -