untitled

1. Program Implementation

Q. How can we get a program going when the physicians at my hospital cannot seem to agree on anything?
A. Education. The medication treatments recommended as part of this program have all been proven to work in prospective randomized placebo controlled trials. Physicians are much more likely to agree when all the evidence supporting treatment is reviewed. Examples of improved treatment rates at other hospitals, which have implemented the program, may also be helpful.

Q. Are strokes of all degrees of severity included in the program?
A. Yes.

Q. Are the eight program goals initiated in all stroke patients regardless of stroke subtype?
A. The eight program goals are initiated in all ischemic stroke patients in whom the suspected underlying mechanism is large vessel atherosclerosis or intracranial branch atherosclerosis (lacunar stroke). Atherosclerosis anywhere in the cervico-cephalic arterial tree including within aortic arch, cervical internal carotid artery and intracranial arteries, qualifies the patient for PROTECT intervention. In patients with other causes of ischemic stroke such as cardioembolic sources, hypercoagulable states, dissections, or vasculitis, who have no evidence of atherosclerosis or CHD risk equivalent, all the goals might not apply.

Q. What about patients not primarily on the Stroke, Neurology or Medicine services, who have suffered strokes?
A. The program can be adopted by all services with appropriate education.

Q. Is the timing for follow-up in the program calculated from discharge from the acute service or from rehab/nursing homes?
A. It is counted from time of discharge form the acute service but can be flexible.

Q. Who does the teaching about lifestyle changes following the cerebrovascular event?
A. Physicians, nurses or other healthcare professionals.

Q. How do you handle the teaching in your patients with altered mental status states and language difficulties?
A. The family members or caregivers can be educated instead.

Q. Are there other potential physical benefits to the patients in terms of prevention of other disease conditions when included in this program?
A. Yes, heart disease and peripheral arterial disease. Please visit the UCLA CHAMP website at www.med.ucla.edu/champ

Q. Can the program only be effectively implemented at a tertiary medical center?
A. No. Our experience has led us to believe that the program can be effectively implemented at all levels of medical care including community hospitals. It is possible that due to an individual hospital's unique human and economic resource situation, certain aspects of the program may be easier to implement than others. However, in such a situation, the program can be tailored to accommodate the hospitals resources. Indeed, of paramount importance, is the availability within the hospital of a formal secondary stroke prevention program geared towards the timely initiation and regularly supervised maintenance of these life-enhancing evidence-based interventions.

Q. What are the benefits to the hospital if treatments rate improve?
A. Lower readmission rates. Improved quality of medical care.

2. Antithrombotics

Q. What is your first choice for first line antithrombotic agent, if any?
A. The American College of Chest Physicians (ACCP) recommends that after noncardioembolic (atherothrombotic, lacunar) stroke, or TIA, patients receive an antiplatelet agent regularly. Aspirin (50 to 325 mg qd), the combination of aspirin and extended-release dipyridamole (25/200 mg bid), or clopidogrel (75 mg qd) are all acceptable options for initial therapy. In patients who are intolerant of aspirin clopidogrel can be used. For cardioembolic events - the ACCP guidelines direct that patients with atrial fibrillation receive long-term oral anticoagulation therapy (goal INR 2.5; range, 2.0 to 3.0) for stroke prevention after a recent stroke or TIA; patients with minor-risk cardiac conditions should be offered antiplatelet agents.

Q. Many stroke patients are elderly and some patients have gait difficulties with significant fall risks. Are these contraindications to warfarin therapy particularly in the context of atrial fibrillation?
A. The incidence of atrial fibrillation (AF) was approximately double for every 10-year increment in age in the Framingham Heart Study cohort. The prevalence of AF is about 5.9% for individuals over the age of 65. For those over age 75, AF is the most important single cause of ischemic stroke. As such, age alone is an indication rather than a contraindication to warfarin treatment. While the risk of bleeding does go up with age, the risk of cardioembolic stroke particularly in atrial fibrillation patients goes up even more steeply with age. Therefore elderly patients generally benefit from anticoagulation in the setting of atrial fibrillation. A severe falling risk may be a contraindication to warfarin but studies have shown that risk is frequently overestimated.

An analysis of five randomized trials comparing warfarin with control in AF patients with a mean age of 69 years found an annual stroke risk of 1.4% for patients treated with warfarin and a stroke rate of 4.5% for the control group. The annual rate of hemorrhage (requiring hospitalization, two units of blood, or occurring intracranially) was 1.3 % in the warfarin group and 1.0% in the control group. Risk of intracranial hemorrhage in the warfarin group was only 0.3% per year.

The only clinical trial (SPAF II) that involved AF patients and reported a substantially higher rate of intracerebral bleeding associated with warfarin (1.8%/y) included participants with a mean age of 80 years and an upper limit of anticoagulation intensity equivalent to an INR of 4.5. This trial also monitored prothrombin time ratios rather than the more accurate INRs. In an analysis of pooled data from three randomized trials, aspirin, which is less efficacious than warfarin, was associated with an annual major hemorrhage rate of 1.0%.

Contraindications to anticoagulation can include patients with marked uncontrollable hypertension (sbp>180mmhg or dbp >100), those with severe dementia, previous intracranial hemorrhage and other bleeding abnormalities.

Overall, in the majority of patients, quality of life estimates for taking warfarin are quite high, whereas 45% of patients in a survey of those at-risk, described a major stroke as a fate equal to, or worse than, death.

Q. How do you deal with antiplatelet failures within the program?
A. A full work up should be instituted and stroke mechanism discovered and addressed. For instance, if the patient has atrial fibrillation then a switch to anticoagulation should be considered. Surgery should be explored for those with significant carotid stenosis and hemodynamic support through volume expansion or discontinuation of antihypertensive medications implemented when indicated. If after a thorough evaluation, antiplatelet therapy is still felt to be the most appropriate therapy, then a change to a different agent (e.g. if stroke occurs on aspirin alone, switch to clopidogrel or ER dipyridamole + aspirin) in conjunction with optimal risk factor control, would be reasonable.

3. Statins and Lipid levels

Q. Are the lipid panels obtained during the first 24 hours of an acute stroke accurate?
A. It appears that serum lipid levels remain stable following acute ischemic stroke, consistent with the absence of an acute phase response. A study by the Northern Manhattan Stroke Group of nineteen subjects who presented with acute moderately severe and severe ischemic strokes showed that there were no significant changes in mean serum lipid levels over a 4-week study period. In addition, there were no significant changes in established acute phase or nutritional markers like C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin.

Q. If all ischemic stroke and transient ischemic attack patients are to be placed on statin therapy within this program regardless of LDL levels, then why bother to check a baseline lipid level?
A. Drawing an admission lipid panel has certain advantages. Patients with complex lipid disorders can be identified early so appropriate follow-up can be arranged. Also, the baseline lipid level can also help to guide the dose of statin needed to reduce the LDL to < 100 mg/dl.

Finally, many patients often like to know what their baseline lipid levels are before being started on treatment. A recent program, "Project ImPACT (Improve Persistence and Compliance with Therapy): Hyperlipidemia," directed by the American Pharmaceutical Association Foundation showed that regular monitoring of lipid levels contributed to increased rates of compliance to 90.1%, up from the average 40% reported in the literature for similar studies.

Q. What happens to a patient, not already on a statin, whose admission LDL level is less than 100 mg/dl?
A. As long as the patients total cholesterol level is above 135mg/dl, such a patient is placed on a fixed, low to intermediate statin dose, regardless of LDL level, in order to reap the other additional stroke protective benefits of statin therapy.

Q. How safe is the chronic use of the statin medications?
A. Statin therapy is rarely associated with side effects. For patients at high risk of heart disease or stroke, the benefits of statins far outweigh their risks. Common side effects include headache, myalgia, fatigue, GI intolerance (indigestion, constipation and abdominal pain) and flu-like symptoms. Increase in liver enzymes occurs in 0.5-2.5% patients in a dose dependent manner. If liver enzymes rise to more than three times their normal levels while a person is taking statins, stopping the drug usually causes the level to fall back to normal. Serious liver problems are quite rare. Myopathy occurs in 0.2-0.4% of patients. This is a reason to stop the medication immediately and check muscle enzymes. Rare cases of rhabdomyolysis do occur. One case of polyneuropathy occurs for every 2,200 patients treated with statins each year. These agents should be cautiously used in those with impared renal function. Overall the best approach to the use of statins is to start with the lowest effective dose, ensure regular clinic followup and obtain intermittent blood tests. The blood tests are done at 6 weeks and 12 weeks and then, if there is no increase in liver enzymes, every 6 to 12 months thereafter.

4. ACE-Is, ARBs, Diuretics, Beta-blockers and blood pressure levels

Q. At what point in the stroke hospitalization process is it permissible to restart antihypertensive agents?
A. Within 48-72 hours as long as the neurologic symptoms have not progressed. Extra caution should be used in patients with moderate to severe intra- or extracranial stenoses.

Q. What level of low blood pressure serves as a contraindication to ACE-Inhibitor/ARB and diuretic therapy in the program?
A. A blood pressure of 105/60 mmhg or mean arterial pressure of 75, precludes ACEI/ARB/Diuretic therapy within the program. If the patient’s pressures are above these values, and the patient is asymptomatic, these medications can be started at low doses as tolerated. Please see the medication algorithm on the PROTECT tools page for further details.

Q. It is generally recommended that MI patients be placed on ACEIs and beta-blockers, but you are recommending that stroke patients go on ACEIs and thiazide diuretics--why the difference?
A. Kindly see the PROGRESS and LIFE trials in the Program Evidence section of this site. Beta-blockers have not been shown to reduce secondary stroke incidence.

Q. If a patient is already on another type of diuretic, do we make a switch to a thiazide diuretic post stroke?
A. If the patient is on spironolactone as a treatment for heart failure or LVH or renal disease then this should not be switched as aldosterone antagonists have been shown to lower mortality in HF by 27% whereas thiazides have not. They also regress LVH and prevent progressive proteinuria, whereas thiazides do not. Loop diuretics have not been shown to reduce stroke. If a loop diuretic is being used for volume control in patients with heart failure, they should not be switched as the thiazide diuretic switch would likely lead to decompensated heart failure. If the patient has none of the aforementioned situations then a switch to a thiazide diuretic can be made after due consultation with the patients primary care physician.

Q. If the patient's blood pressure does not tolerate the use of both ACE-Inhibitor/ARB and diuretic therapy, is there a preference as to which of the aforementioned can be solely prescribed?
A. In such a situation, we would generally use an ACE-I/ARB because of their more attractive side effect profile.

Q. If a patient is admitted to the hospital on an angiotensin receptor blocker should the patient when appropriate be started on an ACE-inhibitor instead?
A. No, either one should suffice.

Q. What about the use of combination pills, e.g., ACE inhibitors/ diuretics or ARB's / diuretics?
A. They are definitely acceptable.

Q. What about the concurrent use of beta-blockers?
A. Beta blockers should be continued if indicated from a cardiac standpoint.

5. Miscellaneous

Q. Why do you check homocysteine levels?
A. Emerging evidence suggests that elevated homocysteine levels are associated with stroke and heart disease and can be treated with proper vitamin therapy.

Q. What is the rationale behind obtaining HbA1c levels during the stroke hospitalization?
A. Various studies including the Framingham study, have shown that diabetes is associated with an increased stroke risk in both men and women independent of age and hypertension. It has also been revealed that mortality from cerebrovascular disease is greatly increased among individuals with elevated blood glucose levels. In spite of all the clear evidence regarding the increased stroke risk associated with diabetes, glycemic control is inadequate for between 30 and 50% of the diabetic population. Obtaining HgbA1c levels during the stroke hospitalization enables us to identify undiagnosed/ poorly maintained diabetics, with the aim of optimizing glycemic control, in order to reduce the risk of microvascular complications including stroke.

Q. How is the Stroke PROTECT program different from the American Heart Association (AHA) "Get with the Guidelines" program?
A. Although both are secondary stroke prevention initiatives, the Stroke PROTECT program strategy differs in a number of ways. First of all, the Stroke PROTECT program's focus is on the implementation of its goals during the initial hospitalization to ensure that patients are definitively started on these life-enhancing therapies. Secondly, within the program there is regular monitoring and feedback, with regard to the patient's compliance with, and awareness of, the 8 program goals, further reinforced by the active inclusion of the patient's family and primary care physician in the program's post-hospital discharge follow up process. Thirdly, the individual aspects of stroke prevention within the PROTECT program are more aggressive based on recent clinical trial evidence (HPS and PROGRESS trials), that is not reflected in the AHA guidelines, as noted by our statin, ace-inhibitor/angiotensin receptor blocker and diuretic goals.

For other questions please email:
Bruce Ovbiagele, M.D.