Dual Antiplatelet Therapy in Progressive Lacunar Strokes

In This Article

Abstract and Introduction

Abstract

Background and Purpose: In 20% to 30% of patients with lacunar strokes, early neurological deterioration (END) occurs within the first days after stroke onset. However, effective treatment strategies are still missing for these patients. The purpose of this study was to analyze efficacy of dual antiplatelet therapy (DAPT) in patients presenting with END.

Methods: Four hundred fifty-eight patients with lacunar strokes and corresponding neuroimaging evidence of lacunar ischemia were retrospectively screened for END, which was defined by deterioration of ≥3 total National Institutes of Health Stroke Scale points, ≥2 National Institutes of Health Stroke Scale points for limb paresis, or documented clinical deterioration within 5 days after admission. Patients with END were treated with DAPT according to in-house standards. Primary efficacy end point was fulfilled if National Institutes of Health Stroke Scale score at discharge improved at least to the score at admission. Secondary end points were Rankin Scale score, further clinical fluctuation, and symptomatic bleeding complications.

Results: END occurred in 130 (28%) of 458 patients with lacunar strokes. Ninety-seven (75%) of these patients were treated with DAPT after END, mostly for 5 days. DAPT was associated with improved functional outcome. The primary end point was met in 68% (66) of patients with DAPT compared with 36% (12) of patients with standard treatment (P=0.0019). Further clinical fluctuations were absent in 79% (77) of patients with DAPT versus 33% (11) of patients without DAPT (P<0.001). Symptomatic bleeding complications were not observed in any patient.

Conclusions: The results demonstrated potential positive effects of DAPT in patients with progressive lacunar strokes.

Introduction

Lacunar strokes represent about 25% of ischemic strokes and are mostly associated with favorable outcomes.^[1,2] However, in 20% to 30% of patients with lacunar strokes, early neurological deterioration (END) occurs within the first days after stroke onset,^[2] and effective treatments are still missing for these patients.

The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial) investigated the efficacy of combination of aspirin and clopidogrel for 90 days regarding reduction of stroke recurrence in patients with minor stroke and high-risk transient ischemic attack, defined by National Institutes of Health Stroke Scale (NIHSS) score of ≤3 or ABCD^[2] score (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) of ≥4, and demonstrated a reduced risk for major ischemic events but an increased risk for major hemorrhage with combined treatment.^[3] However, this trial did not distinguish between stroke recurrence and stroke progression as cause for END nor did clarify the inclusion of patients with lacunar strokes.^[4]

Our institutional guidelines allow the initiation of dual antiplatelet therapy (DAPT) in lacunar stroke patients presenting with END as off-label therapy. The aim of this retrospective cohort study was to evaluate the efficacy of DAPT in patients with progressive lacunar strokes.

Table 1. Clinical Characteristics of Patients With and Without END Subdivided in Patients With and Without Thrombolysis at Admission
Clinical Characteristics	Patients Without END (n=238)		Patients With END (n=130)
Clinical Characteristics	With Thrombolysis (n=34)	Without Thrombolysis (n=294)	With Thrombolysis (n=32)	Without Thrombolysis (n=98)
Age, median; (range)	74 (38–90)	69.7 (37–89)	69.3 (42–91)	70 (42–89)
Female gender, n	13	108	4	29
Hypertension, n	32	275	24	90
Diabetes mellitus, n	16	84	6	26
HbA1c, median (IQR)	6.1 (1.6)	5.7 (1.3)	5.7 (0.5)	5.8 (1)
Hypercholesterolemia, n	22	188	19	73
LDL-cholesterol, median (IQR)	112 (63)	120 (49)	124.5 (39)	127 (49)
Smoker, n	9	103	13	30
Prior TIA, n	…	7	…	…
Lacunar syndrome, n
Motor paresis without sensory symptoms	9	70	12	33
Ataxic paresis	3	64	2	23
Senso-motor paresis	14	58	17	38
Sensory symptoms without paresis	2	35	…	2

Hypertension, diabetes mellitus, or hypercholesterolemia was defined as diagnosis made before admission or systolic blood pressure ≥140 mm Hg, HbA1c ≥6.5, or LDL-cholesterol ≥120 mg/dL. For lacunar syndromes, only symptoms regarding paresis and sensory symptoms were revised. Most patients had additional facial paresis or dysarthria. END indicates early neurological deterioration; HbA1c, hemoglobin A1c; IQR, interquartile range; LDL, low-density lipoprotein; and TIA, transient ischemic attack.

Table 2. Efficacy of DAPT in All Patients With Progressive Lacunar Strokes and Subdivided in Patients With and Without Thrombolysis
End Points	All Patients (n=130)			Patients With Thrombolysis (n=32)			Patients Without Thrombolysis (n=98)
End Points	DAPT (n=97)	No DAPT (n=33)	P Value	DAPT (n=17)	No DAPT (n=15)	P Value	DAPT (n=80)	No DAPT (n=18)	P Value
Fulfilled primary end point	66 (68%)	12 (36%)	0.0019	14 (82%)	8 (53%)	0.13	52 (65%)	4 (22%)	0.0013
Fulfilled secondary end points
Rankin Scale score	78 (80%)	24 (73%)	0.46	16 (94%)	9 (60%)	0.03	62 (78%)	15 (83%)	0.76
No further fluctuation	77 (79%)	11 (33%)	<0.001	15 (88%)	9 (60%)	0.1	62 (78%)	2 (11%)	<0.001
No bleeding complications	97	33	…	17	15	…	80	18	…

For efficacy end points, NIHSS and Rankin Scale scores were compared between discharge and admission. P values of DAPT efficacy were calculated with Fisher exact test. DAPT indicates dual anti-platelet therapy; and NIHSS, National Institutes of Health Stroke Scale.