Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.


Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. Methods We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. Results During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. Conclusions In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days.

Vigorous Exercise May Significantly Lower Your Stroke Risk.


Story at-a-glance

  • A new study shows that vigorously exercising at least four times per week can reduce your risk of a stroke, especially if you’re a man; the results are unclear if you’re a woman
  • This study (and some prior studies) seem to suggest that women may respond better to less vigorous exercise, such as walking, although most studies don’t take into account that all forms of cardio are not equal
  • Vigorous exercise is important for overall health, but conventional cardio is risky due to the extreme stress on your heart, which may cause inflammation, plaque, arrhythmias, and even heart attack or stroke
  • Regardless of your gender or age, you can optimize your exercise benefits by doing high-intensity interval training, which pushes your body hard enough for a challenge while allowing adequate time for recovery and repair
  • You can further reduce your stroke risk by getting adequate sunshine for the vitamin D and nitric oxide benefits, grounding yourself to the earth, and consuming adequate fiber, especially the soluble variety.
  • Vigorous Exercise

Exercise is one of the best ways to keep yourself healthy. The benefits of exercise for lowering your heart attack risk, reducing stress, and helping to prevent obesity and diabetes are widely known.

Well, now you can add another big one to your list of benefits from breaking a sweat: reduced risk of stroke.

The American Heart Association reports 800,000 Americans suffer from stroke each year. Stroke is the leading cause of disability in the US and the fourth leading cause of death. Up to 80 percent of strokes are preventable, because for the most part, strokes are the result of unhealthy lifestyle choices.

Recent research published in the journal Stroke1 found that, if you’re inactive, you have a 20 percent higher risk for having a stroke or mini-stroke (transient ischemic attack) than people who exercise enough to break a sweat at least four times a week.

The study involved more than 27,000 Americans for an average of 5.7 years, male and female, Caucasian and African-American. It included a larger proportion of people from the “Stroke Belt” states, where stroke rates are higher (Virginia, Tennessee, the Carolinas, Mississippi, Louisiana, Georgia, Florida, Arkansas, and Alabama).

The connection between vigorous exercise and stroke risk was very clear in men, but interestingly, less clear in women. Lead researcher Dr. Michelle McDonnell speculates that women may benefit more from less vigorous exercise, such as walking, which this study did not examine.2

Stroke Rates Increasing Among Younger People

Your risk of stroke increases with age, with most occurring after age 55. However, younger people are increasingly at risk, according to the latest statistics.

The rate of strokes among younger people (under age 55) nearly doubled between 1993 and 2005.3 The primary driving forces behind this are increasing rates of obesity, diabetes and high blood pressure—which can all increase your risk for suffering a devastating stroke.

Stress is also a significant risk factor for stroke, just as it is for heart attack. According to a 2008 study in Neurology,4 the more stressed you are, the greater your stroke risk—especially a fatal one. Heart attacks and stroke have many other risk factors in common, including:

A Stroke Is a ‘Heart Attack in Your Brain’

Heart attacks and strokes are both events in which cells die from lack of oxygen. With a heart attack, your heart is the affected organ, but with a stroke, it’s your brain.

A stroke involves either a rupture of an artery that feeds your brain (hemorrhagic stroke), or an obstruction of blood flow (ischemic stroke), with the ischemic type representing 75 percent of all strokes. In both types, your brain does not get enough oxygen and glucose, in addition to pooled blood putting physical pressure on areas of your brain.

And then there are mini-strokes, or TIAs (transient ischemic attacks). Each year, as many as 500,000 Americans experience TIAs, caused by temporary blockages in cerebral blood vessels, with symptoms similar to those of a stroke but oftentimes milder and shorter in duration.

Although less imminently dangerous than a full stroke, they should NOT be ignored. According to an article by Loyola University Medical Center’s journal,Expert Review of Neurotherapeutics, 10 to 15 percent of people experiencing TIAs will experience a full-blown stroke within three months, and 40 percent of those will occur in the first 24 hours.5 Stroke victims experience a variety of sudden symptoms, the most common being those listed in the table that follows.

Weakness, numbness, or paralysis in one arm or leg Sudden speech difficulties
Loss of coordination or trouble walking Confusion, memory loss or other sudden cognitive deficit
One-sided facial paralysis or facial droop Sudden visual problems
Sudden severe headache Dizziness

If you or someone you love suffers a stroke, getting medical help quickly can mean the different between life and death, or permanent disability. This is an area where conventional medicine excels, as there are emergency medications that can dissolve a blood clot that is blocking blood flow to your brain. If done quickly enough, emergency medicine can prevent or reverse permanent neurological damage—but you typically need treatment within one hour, which means the faster you recognize the warning signs, the better the prognosis. The National Stroke Association recommends using the FAST acronym to help remember the warning signs of stroke:6

F = FACE: Ask the person to smile. Does one side of the face droop?

A = ARMS: Ask the person to raise both arms. Does one arm drift downward?

S = SPEECH: Ask the person to repeat a simple phrase. Does their speech sound slurred or strange?

T = TIME: If you observe any of these signs, call 9-1-1 immediately.

Exercise Reduces Stroke Risk—But ONLY the Right Kind of Exercise

There have been a number of scientific studies about the benefits of exercise in stroke prevention, and recovery from stroke. Differences between men and women, in terms of the type of exercise that is best, have appeared in more than one study to date. The thing to keep in mind is, not only is it important to get enough exercise, but you must be doing thecorrect kind of exercise if you want to reap the benefits, which I’ll be discussing in more detail shortly. Further research is definitely needed in order to clarify how much and what type of exercise is best for men and women, in terms of preventing stroke.

  • ·A 2013 study published in Stroke7 concluded that walking at least three hours per week reduces stroke risk in womenbetter than inactivity, but also better than high intensity cardio. This may have something to do with the inordinate amount of physical stress “conventional cardio” has on the heart, and the fact that people generally do too much of it for too long. Perhaps women are more susceptible to these risks than men.

Conventional cardio can cause arrhythmias, and in some cases, atrial fibrillation (A-fib), which is a known risk factor for stroke. It would be of value to study the effects of high-intensity interval training (HIIT) on stroke risk in both men and women, which is very different than conventional cardio. But unfortunately, when cardio has been studied, it’s usually the conventional type.

  • ·In 2009, a study in Neurology8 found that vigorous exercise reduces stroke risk in men, as well as helping them recover from a stroke better and faster. However, moderate to heavy exercise was not found to have a protective effect for women. I would expect the right type of cardio would be found to lower stroke risk in both men and women, but those studies have not yet been done.
  • ·In 2012, Canadian researchers found that stroke patients who exercised were able to improve problems with their memory, thinking, language and judgment by close to 50 percent in just six months. Notable improvements in attention, concentration, planning and organizing, as well as benefits to muscle strength and walking, were seen among stroke patients who exercised.
  • ·In 2008, a study published in Neurology9 found that people who are physically active before a stroke have less severe problems and recover better, compared to those who didn’t exercise prior to their stroke.

Several recent scientific studies indicate that conventional cardio, especially endurance exercises such as marathon and triathlon training, pose significant risks to your heart, some of which may be irreversible and life threatening. Long-distance running can lead to acute volume overload, inflammation, thickening and stiffening of the heart muscle and arteries, arterial calcification, arrhythmias, and potentially sudden cardiac arrest and stroke.

I don’t think anyone can argue against the fact that vigorous exercise is beneficial to your heart and brain, but conventional cardio is just not the way to do it. This could be why the cardio benefits to women are not being detected in these studies… but that’s just a theory.

Ideally, to get the most benefits from your exercise, you need to push your body hard enough for a challenge while allowing adequate time for recovery and repair to take place. One of the best ways to accomplish this is with HIIT, or high intensity interval training, which consists of short bursts of high-intensity exercise, as opposed to extended episodes of exertion. This is a core part of my Peak Fitness program, which Phil Campbell was instrumental in helping me develop. Briefly, a Peak Fitness routine typically includes:

  • ·Warm up for three minutes
  • ·Exercise as hard and fast as you can for 30 seconds. You should feel like you couldn’t possibly go on another few seconds
  • ·Recover for 90 seconds
  • ·Repeat the high intensity exercise and recovery cycle 7 more times

You can do HIIT by running/sprinting (if you love running), or by using gym equipment such as a treadmill or elliptical machine, or you can accomplish the same thing without running at all by doing super-slow weight training, as I demonstrate in the video above. HIIT maximizes your secretion of human growth hormone (HGH), optimizes your metabolism and helps regulate your insulin and blood sugar. And it takes far less time than training for a marathon! You can do a complete Peak Fitness workout in 20 minutes or less.

The Importance of Recovery

Remember, adequate recovery is crucial between workouts. This includes not only resting your body, but also giving it the nutrients it needs for complete recovery. Your post-workout meal can support or impair your recovery. For instance, consuming a fast-assimilating protein such as high-quality whey protein within 30 minutes of your workout will essentially “rescue” your muscles out of their catabolic state and supply them with the nutrients they need to make their repairs. Any sort of intense exercise should also be balanced with strength training, proper stretching, core strengthening, stress reduction, good sleep and an optimal nutrition plan. You’ll find much more information about HIIT and other types of exercise in the fitness section of my website.

Three Bonus Tips for Stroke Prevention

Here are three simple tips for further lowering your stroke risk—but by no means is this a comprehensive list. For more information about lifestyle changes specific to preventing stroke, please refer to this recent stroke prevention article.

  1. SunshineSunlight causes your skin to produce nitric oxide, a critical compound for optimizing your blood pressure, which reduces your risk for both heart attack and stroke. Nitric oxide enhances blood flow, promotes blood vessel elasticity, and functions as a signaling molecule in your brain and immune system.

And of course, exposing your skin to the sun also helps optimize your vitamin D level, which should be between 50 and 70ng/ml, or higher if you have a serious illness.

  1. Grounding. Walking barefoot on the Earth, aka “earthing” or “grounding,” has a potent antioxidant effect that helps alleviate inflammation throughout your body. It also makes your blood less prone to “hypercoagulation”—so, less apt to clot—and that reduces your stroke risk.

There is a constant flow of energy between our bodies and the earth. When you put your feet on the ground, you absorb large amounts of negative electrons through the soles of your feet, which reduces the tendency of your blood cells to “clump together.” Technically, grounding increases the zeta potential of your red blood cells causing them to repel each other and become less sticky, very similar to a natural anticoagulant.

Research has demonstrated that it takes about 80 minutes for the free electrons from the earth to reach your blood stream and transform your blood, so make it a point to regularly walk barefoot on grass or on wet sand for about 90 minutes to two hours, if possible.

  1. Fiber. If you eat more fiber, you will probably reduce your chances of a stroke, according to a report in the journalStroke.10 For every seven grams more fiber you consume daily, your stroke risk is decreased by seven percent, according to this study.

Fiber is the non-digestible part of plants, which can be either soluble or non-soluble; soluble fiber was found to lower stroke risk the most. Soluble fiber can also help nurture beneficial gut bacteria, which are critical for good health. The American Heart Association and UK health authorities recommend adults consume 25 grams of dietary fiber each day, but I think you should get upwards of 32 grams per day and most Americans don’t get anywhere near this amount.

Great sources of fiber include seeds (especially chia, psyllium, sunflower, and organic flax), berries, vegetables such as broccoli and cauliflower, root vegetables and tubers (including onions and sweet potatoes), almonds, and beans (legumes).

Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack.


Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.

METHODS

In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.

RESULTS

Stroke occurred in 8.2% of patients in the clopidogrel–aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel–aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.

CONCLUSIONS

Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage.

Source: NEJM

Dual Antiplatelet Therapy in Acute Transient Ischemic Attack and Minor Stroke.


Some patients with stroke and transient ischemic attack (TIA) of the brain are at high risk for early recurrent stroke, usually due to arterial thromboembolism.1,2 Aspirin reduces the risk of early recurrent stroke by only 12% (95% confidence interval [CI], 3 to 20).3 Adding clopidogrel to aspirin in patients with acute coronary syndromes reduces the risk of recurrent vascular events by 20% (95% CI, 10 to 28) but increases the risk of major bleeding by 38% (95% CI, 13 to 67).4 For patients with acute ischemic stroke, who are prone to early spontaneous hemorrhagic transformation of infarcted brain, adding clopidogrel to aspirin may cause more major bleeding than may otherwise occur in acute coronary syndromes. Among 731 patients with acute ischemic stroke or TIA (onset within the previous 3 days) enrolled in five small trials, the addition of clopidogrel to aspirin was associated with nonsignificant trends toward a reduction in recurrent stroke (4.5% with clopidogrel and aspirin, as compared with 6.6% with aspirin alone) and an increase in major bleeding (1.1% and 0%, respectively).5

Wang and colleagues now report in the Journal the impressive results of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial.6 Among 5170 Chinese patients with acute minor ischemic stroke or TIA (onset within the previous 24 hours) at high risk for recurrence, the addition of clopidogrel to aspirin reduced the relative risk of recurrent stroke at 90 days by 32% (8.2% vs. 11.7%; hazard ratio, 0.68; 95% CI, 0.57 to 0.81; absolute risk reduction, 3.5 percentage points). The effect was consistent among 11 predefined subgroups. There was no difference between the group that received both clopidogrel and aspirin and the group that received aspirin alone in the incidence of moderate or severe hemorrhage (0.3% in each group; P=0.73) or hemorrhagic stroke (0.3% in each group; P=0.98).

The CHANCE investigators completed a large, scientifically rigorous trial that proves the concept that dual antiplatelet therapy can be more effective than single antiplatelet therapy in preventing early recurrent stroke in patients with acute symptomatic atherothrombosis (predominantly intracranial) of the brain. Moreover, the absolute benefits of dual antiplatelet therapy can be substantial in patients at high risk for recurrent stroke1; treating 29 patients for 90 days with clopidogrel plus aspirin for the first 21 days, followed by clopidogrel alone from day 22 to day 90, prevented one stroke, as compared with aspirin alone. Indeed, most of the absolute benefit of clopidogrel plus aspirin is realized within the first few days after TIA and ischemic stroke, when the underlying atherosclerotic plaque is most unstable and the risk of recurrence is highest.

The safety results show that dual antiplatelet therapy can be given without excess harm in patients with acute focal brain ischemia, provided that patients have a low risk of hemorrhagic transformation — no fresh brain infarction (i.e., TIA) or a very small volume of fresh brain infarction (i.e., minor ischemic stroke). The CHANCE investigators had to screen 41,561 patients with stroke or TIA to find 5170 appropriate patients (12.4%). Hence, the results cannot be generalized to most patients; the study excluded patients with major ischemic stroke, who are at risk for hemorrhagic transformation, and patients with TIA due to isolated sensory, visual, or vertiginous syndromes, who are at low risk for recurrence.1 The results may also not apply to non-Chinese patients with different forms of underlying arterial disease (e.g., a higher prevalence of extracranial large-artery atherosclerosis) and different prevalences of genetic polymorphisms of liver cytochrome P-450 (CYP) isozymes, which metabolize clopidogrel to its active metabolites. The absolute benefits of clopidogrel plus aspirin observed in this trial may also not be realized in persons and populations at lower absolute risk for recurrent stroke, such as those with a low prevalence of risk factors for recurrent stroke and those with access to effective secondary stroke prevention. Finally, the results of this trial cannot be generalized beyond 90 days after ischemic stroke, when the cumulative risks of bleeding with clopidogrel plus aspirin, as compared with aspirin or clopidogrel alone, offset the benefits.7-9

The implication of this trial is that Chinese patients with acute TIA or minor ischemic stroke (onset within the previous 24 hours) who are at high risk for recurrence should be regarded as a medical emergency. They should be treated immediately with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone, for a total of 90 days, before continuing long-term treatment with clopidogrel, aspirin, or the combination of aspirin and extended-release dipyridamole. A bolus loading dose of at least 162 mg of aspirin and 300 mg of clopidogrel is required on day 1 to rapidly inhibit platelet aggregation, given that starting with daily doses of 75 mg of aspirin and clopidogrel takes several days to produce maximal inhibition of platelet aggregation. The benefits of dual antiplatelet therapy are greatest in the first days after TIA and ischemic stroke.

I think that clinicians should continue to enroll non-Chinese patients with acute TIA and minor ischemic stroke into ongoing large clinical trials of the safety and efficacy of dual and triple antiplatelet therapy.10,11 Moreover, I hope that researchers will evaluate new antiplatelet agents (e.g., ticagrelor and prasugrel) and new anticoagulant agents (e.g., rivaroxaban) that are effective in atherothrombotic acute coronary syndrome in patients with acute TIA and minor ischemic stroke due to arterial thromboembolism.

Source: NEJM

 

Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack.


Transient ischemic attack (TIA) and acute minor ischemic stroke are common and often lead to disabling events. In China, there are approximately 3 million new strokes every year, and approximately 30% of them are minor ischemic strokes.1,2 The incidence of TIA in China has not been determined, but on the basis of the incidence in other countries, there are probably more than 2 million TIAs annually in China.3-5 The risk of another stroke occurring after a TIA or minor stroke is high, with approximately 10 to 20% of patients having a stroke within 3 months after the index event; most of these strokes occur within the first 2 days.5-8

The role of antiplatelet therapy for secondary stroke prevention has been well established. However, aspirin is the only antiplatelet agent that has been studied in the acute phase of stroke, during which its benefit is modest.9,10 Aspirin and clopidogrel synergistically inhibit platelet aggregation,11,12 and such dual therapy reduces the risk of recurrent ischemic events in patients with the acute coronary syndrome.13,14 Large-scale trials of secondary prevention of ischemic events after stroke have not shown a benefit of the combination of clopidogrel and aspirin.15-17 However, these trials did not study the early, high-risk period after stroke, they included some patients with strokes of moderate severity, and they included few if any patients with TIA. Three small pilot trials have shown trends toward a benefit of the combination therapy and minimal safety concerns in patients with minor stroke or TIA.18-20

We conducted the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial to test the hypothesis that 3 months of treatment with a combination of clopidogrel and aspirin would reduce the risk of recurrent stroke, as compared with aspirin alone, among patients with acute high-risk TIA or minor ischemic stroke.

DISCUSSION

In this large-scale trial involving patients with high-risk TIA or minor ischemic stroke, we found that the addition of clopidogrel to aspirin within 24 hours after symptom onset reduced the risk of subsequent stroke by 32.0%, as compared with aspirin alone. Event rates during this early period were very high, and clopidogrel was associated with an absolute risk reduction of 3.5 percentage points, equivalent to a number needed to treat of 29 patients to prevent one stroke over a period of 90 days. Combination therapy with clopidogrel and aspirin, as compared with aspirin alone, was not associated with an increased incidence of hemorrhage, although there was a worrisome trend in overall bleeding toward more events with the combination therapy.

The results of our trial differ from those of other trials of combination therapy with clopidogrel and aspirin after cerebral ischemic events.7,8,17 One possible explanation is that, unlike previous trials, our trial targeted a population at particularly high risk for recurrent ischemia and at low risk for hemorrhage. Previous trials included patients with more severe strokes than our trial did, and they did not enroll patients in the first hours after an index minor stroke or TIA, during which the risk of recurrent ischemia is particularly high. This may explain why other trials did not show a reduction in the risk of ischemic events but did show an increased risk of hemorrhage.

In our study, the curves for survival free of stroke were particularly steep in the first few days, during which the curves representing the treatment groups diverged dramatically. Subsequently, the rates of stroke were similar. This suggests that the requirement for randomization within 24 hours after the onset of symptoms, with nearly half the patients enrolled within 12 hours (and treated shortly thereafter), was important. Although we did not see a relative difference in the efficacy outcome between patients randomly assigned to a study group within 12 hours and those assigned after a longer interval, absolute event rates were higher among those who were enrolled within 12 hours. In clinical practice, treatment with clopidogrel and aspirin as soon as possible after symptom onset is likely to produce the greatest absolute benefit, since ischemic event rates are highest in the initial hours after symptoms appear.

Our trial was conducted entirely in China, a country with approximately 150 to 250 deaths from stroke per 100,000 persons per year, which is five times as high as the rate in the United States.23Although diagnostic tools and therapies commonly used in the United States and Europe are available in most hospitals in China, some patients cannot afford this level of care.24,25 Secondary prevention practices are also less rigorous in China, where rates of treatment of hypertension, diabetes, and hyperlipidemia are low, as shown in our study population (Table S3 in theSupplementary Appendix). Furthermore, the distribution of stroke subtypes in China differs from that in more developed countries; China has a higher incidence of large-artery intracranial atherosclerosis25 and a higher prevalence of genetic polymorphisms that affect the metabolism of clopidogrel.26 The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial (ClinicalTrials.gov number, NCT00991029), sponsored by the National Institutes of Health, which is similar to our trial, is now enrolling patients at sites primarily in the United States.27 The POINT trial is assessing a higher loading dose of clopidogrel (600 mg) and a narrower time window (treatment within 12 hours after symptom onset) than were used in our study.

Several common clinical conditions mimic TIA, including seizures, migraine, peripheral vertigo, syncope, and anxiety.28 To minimize the risk of enrolling patients with TIA mimics, we excluded all patients with isolated sensory symptoms, isolated visual changes, or isolated dizziness or vertigo without evidence of acute infarction on baseline CT or MRI of the head. In addition, enrollment of patients with TIA was limited to those with a high ABCD2 score (≥4) to increase the likelihood that spells were due to true TIAs and to ensure that we were enrolling patients who were at high risk for subsequent ischemic events.29 The risk of subsequent stroke in the trial was high for this patient population, suggesting that our strategy was successful. Our findings may not apply to other populations of patients with ischemic events.

In conclusion, our study shows that among patients with high-risk TIA or minor ischemic stroke who are initially seen within 24 hours after symptom onset, treatment with clopidogrel plus aspirin for 21 days, followed by clopidogrel alone for a total of 90 days, is superior to aspirin alone in reducing the risk of subsequent stroke events. The combination of clopidogrel with aspirin did not cause more hemorrhagic events in this patient population than aspirin alone.

Source: NEJM

Stroke patients with cerebral microbleeds on MRI scans have arteriolosclerosis as well as systemic atherosclerosis.


Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio–ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age=70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, P<0.001). In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12–2.00; P=0.006), advanced WMH (OR, 4.78; 95% CI, 1.55–14.74; P=0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16–9.81; P=0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

Source: Hypertension Research/nature.

Even Minor Strokes Can Cause Long-Term Disability.


In a prospective study, 15% of patients had not recovered full functioning 3 months after transient ischemic attack or minor ischemic stroke.

Most randomized trials of thrombolytic therapy for acute ischemic stroke have excluded patients with minor neurological deficits. A substantial proportion of these patients leave the hospital with some form of disability, but whether that disability persists in the long term remains uncertain. To address this uncertainty, researchers conducted a prospective observational study to ascertain 3-month functional outcomes in patients with transient ischemic attack (TIA) or minor stroke.

The CATCH study enrolled 510 patients with high-risk TIA (focal weakness or speech dysfunction lasting 5 minutes) or minor ischemic stroke (NIH Stroke Scale [NIHSS] score 3). Patients who received thrombolysis or had preexisting disability were excluded. All patients underwent baseline computed tomographic (CT) angiography.

Among 499 patients with complete follow-up, 15% had disability (modified Rankin Scale [mRS] score 2) at 3 months. Twenty-six percent of these patients had a recurrent ischemic event; in the remaining 74%, long-term disability presumably resulted from the original event. Disability rates ranged from 7% among patients with a baseline NIHSS score of zero, to 22% among those with a score of 3. In patients without recurrent events, disability was predicted by ongoing symptoms at the time of evaluation (odds ratio, 2.4) and large-vessel occlusion or acute infarction on CT angiography (OR, 2.4). These predictive associations were also significant when patients with recurrent events were included.

Comment: The authors justifiably call for more research into why patients without recurrent events end up with disability, particularly when there are no apparent deficits at baseline. In the meantime, this study should motivate us to ensure adequate follow-up and rehabilitation for patients with seemingly minor ischemic events. Additionally, these results support the use of thrombolytic therapy for minor ischemic stroke, and they help make a case for acute-treatment trials in this population.

Source:Journal Watch Neurology

 

Even Small Strokes Can Cause Disability.


Some patients with transient ischemic attack and minor stroke become disabled within 3 months, even without having a recurrent vascular event, a study in Stroke shows.

Of about 500 prospectively identified patients with TIA or minor stroke (modified Rankin Scale score less than 2), 15% were disabled (mRS 2 or above) at 3 months. Those with recurrent events were significantly more likely to become disabled than those without them (53% vs. 12%). However, three quarters of those who became disabled had no recurrent event to explain the disability, but instead deteriorated after the initial event.

Predictors of disability were baseline abnormalities on computed tomography or CT angiography, ongoing symptoms at presentation, female sex, and diabetes.

The authors conclude that “treatment options such as thrombolysis should be considered” in patients with acute stroke, symptomatic intracranial or extracranial occlusion, or at least 50% stenosis, as well as ongoing symptoms, because they are at highest risk for disability.

Source: Stroke