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Stroke. 2007;38:1427-1429
Published online before print March 29, 2007, doi: 10.1161/STROKEAHA.106.480459
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(Stroke. 2007;38:1427.)
© 2007 American Heart Association, Inc.


Editorials

So, What’s New?

Lewis H. Kuller, MD, DrPH

From the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pa.

Correspondence to Lewis H. Kuller, MD, DrPH, Department of Epidemiology, University of Pittsburgh, 130 North Bellefield Ave, Rm 550, Pittsburgh, PA 15213. E-mail kullerl{at}edc.pitt.edu


Key Words: adherence • lipids • secondary prevention

See related article, pages 1557-1564.

Does reduced medication access after a stroke increase the risk of recurrent stroke and subsequent disability? How many recurrent strokes in the population are attributable to poor control of risk factors, such as lack of treatment of elevated blood pressure (BP), high cholesterol, diabetes or the use of antiplatelet agents, etc? The article by Levine et al1 notes that {approx}9% or an estimated 76 000 stroke survivors in the US were unable to afford their necessary medications. The characteristics of such individuals are, as would be expected from previous studies, lower income, lack of insurance, multiple diseases requiring high cost of treatments, lack of usual source of care and lack of disposable income to pay for the drugs.

The critical question is if we could enhance adherence, would it have any effect on outcomes? The current report by Levine et al did not measure whether the lack of funds to pay for the drug therapy had any impact on the control of risk factors or whether it had any effect on the clinical outcomes of poststroke patients. However, other studies have clearly documented that adherence to drug therapies is an important component of reducing risk of disease. Most likely, levels of risk factors and adherence to therapies are the 2 critical variables that determine risk of both incident stroke and recurrent stroke.2–7

In 2001, Qureshi reported in 1252 survivors of myocardial infarction and stroke from the National Health And Nutrition Examination Survey (NHANES) III that only 53% of hypertensives were controlled. Blood glucose in diabetics was controlled in only about 50% and cholesterol was poorly controlled in 46%. About 18% of individuals were also still smoking cigarettes.8

In January 2002, Dr Claude Lenfant, then Director of the National Heart, Lung, and Blood Institute, reported on the sad state of control of elevated BP. He noted that support for national high-BP control was being dissipated at a time when compelling new research had contributed to the benefits of such therapy to prevent disease.9

So what’s new? Not very much. In 1965, John Howard reported that differences in drug therapy for hypertension probably accounted, in part, for the large racial differences in hypertensive mortality in the US. Wilber and Barrow in 1969 in a community-based study in rural Georgia noted that only 15% of hypertensives were under good BP controls. Doctors in the community had lost track of 56% of their hypertensive patients and their treatment within 3 months. The use of a well-organized program, including both nurses and health educators for detailed follow-up, increased the control of BP to over 80% in the community.10

In 1972, the Hypertension Study Group of the Intersociety Commission on Heart Disease Resources noted that community BP programs to treat and control hypertension were urgently needed.11

The Hypertension Detection Follow-up Program (HDFP) was a community-based clinical trial in the 1970s which compared usual referred care with special care. The special-care group received their BP medication, primarily diuretics and reserpine-free, and had excellent follow-up using health counselors and nurses, resulting in very good control of BP and substantial reduction in both stroke and total mortality in the special-care versus referred-care group. However, once the program had stopped at the end of the trial, adherence to the therapy was reduced.12

In the late 1970s, the Mayo Clinic group developed effective BP control programs in 3 defined rural communities in Minnesota.13

In contrast to the very high levels of adherence and control of BP in the HDFP, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) provided specific antihypertensive drugs to participants through their physicians’ offices and clinics but not as an aggressive follow-up program as in HDFP. The control of BP 140/90 mm Hg had improved from 27.4% at randomization to {approx}66% at 5 years of follow-up, excluding individuals who had dropped out of the study. Practically all of the individuals were on antihypertensive therapy at entry to the study. BP control was worse for those with comorbid conditions. The ALLHAT suggested that availability of drugs without extensive health counselor and adherence follow-up does not necessarily eliminate the problem of nonadherence, even in a very selected population in this clinical trial.14

Wang et al evaluated treated hypertensives over age 65 in the Pennsylvania PACE drug treatment program that provided medications at a very low copayment of $6 for low income individuals. Among hypertensives in 1999 (n=5517) who were being treated, the use of antihypertensive therapy in 2000, one year later, varied according to comorbid conditions from 83% of those with no comorbid conditions to only 76.4% for hypertensives with a history of depression. There was no association of a history of stroke and the use of antihypertensive medication in 2000 among the hypertensives who were on therapy in 1999.15,16

The problem of nonadherence to drug therapy and poor control of risk factors is not unique to the US but has also been noted in Europe. The control of BP in Europe appears to be even worse than in the US in spite of different healthcare delivery systems and availability of free or very low-cost drug therapies.17,18

The costs of drug therapy and the availability of insurance may be important but not the only barriers to maximizing adherence. A systems approach, including community education and outreach as was done in the HDFP, the studies in Georgia in the 1960s and the Mayo Clinic in the 1970s, may be necessary to maximize adherence and reduce risk of recurrent stroke.

The Robert Wood Johnson Foundation and, more recently, other organizations including Medicare have supported improved chronic disease management. These programs were modeled after a chronic disease management approach that was developed at the Group Health Cooperative of Puget Sound by Dr Edward Wagner et al. The emphasis in these models is very similar to the HDFP approach with an emphasis on team management of chronic diseases and community participation. Most of the emphasis in these programs focused on managing disability and complex therapies for individuals with existing disease and not with maintaining long-term adherence to behavioral or drug therapies that modify risk factors to prevent both the incidence and recurrent stroke.19,20

The failure to control risk factors before and after a stroke likely has a major impact on the individual’s risk of disease, probably increasing not only risk of recurrent stroke and disability but also of dementia. The lifetime risk of stroke in a middle-aged individual, for example, is about 1 in 6, as is the risk for dementia. In the Framingham Heart Study, individuals with normal BP had half the lifetime risk of stroke as the rest of the population. High BP remains an important risk factor for recurrent stroke.20–22 At least 20% to 25% of stroke patients developed vascular-type dementia after the stroke, and with each recurrent stroke and further damage to the brain, the risk of dementia and cognitive decline continues to increase. It is very likely that vascular disease in the brain attributable to uncontrolled risk factors is an important contributor not only to the vascular dementia but also to the development of Alzheimer disease.23,24

Unfortunately, it is unlikely that the sorry state of preventive health care and control of risk factors before or after a stroke will change with more publications and reports. At present, most of the evidence suggests that community-based outreach with health counselors, nurses and other health professionals working with physicians in models like HDFP probably provide the most successful long-term approaches to maximize adherence and reduction of risk factors and likely decreases in morbidity and mortality. Free or low-cost medications alone as well as reducing the costs of health services are valuable but probably are not the only solutions. There, unfortunately, appears to be little incentive to support the personnel needed for these programs.

We are very unlikely to find the gene for adherence nor the specific genes that would make it possible to individualize those who do or do not need risk-factor modification. We certainly do not need more reports on nonadherence or process evaluation to describe lack of adherence or more committee meetings and recommendations. We lack a real commitment to improving the quality of long-term preventive care for both primary and secondary prevention of stroke. Fifty years of articles describing the problem and many demonstration projects are clearly enough, and it is time to require actions that will result in practically all patients with stroke or similar chronic disease to have good to excellent control of their risk factors. We could hypothesize that both prevention and treatment of the risk factors and adherence to risk-factor modification will have the biggest single impact on reduction of morbidity and disability attributable to initial and recurrent stroke and vascular-related dementia at the present time.

Acknowledgments

Disclosures

None.

Footnotes

The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.

References

1. Levine DA, Kiefe CI, Howard G, Howard VJ, Williams OD, Allison JJ. Reduced medication access: a marker for vulnerability in US stroke survivors. Stroke. 2007; 38: 1557–1564.[Abstract/Free Full Text]

2. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke. 2006; 37: 577–617.[Abstract/Free Full Text]

3. Mohr JP, Thompson JLP, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, Jackson CM, Pullicino P; for the Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.[Abstract/Free Full Text]

4. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet. 2006; 367: 1665–1673.[CrossRef][Medline] [Order article via Infotrieve]

5. Di Mascio R, Marchioli R, Tognoni G. Cholesterol reduction and stroke occurrence; an overview of randomized clinical trials. Cerebrovasc Dis. 2000; 10: 85–92.[CrossRef][Medline] [Order article via Infotrieve]

6. Collins R, Armitage J, Parish S, Sleight P, Peto R. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004; 363: 757–767.[CrossRef][Medline] [Order article via Infotrieve]

7. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006; 355: 549–559.[Abstract/Free Full Text]

8. Qureshi AI, Suri MFK, Guterman LR, Hopkins LN. Ineffective secondary prevention in survivors of cardiovascular events in the US population: report from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2001; 161: 1621–1628.[Abstract/Free Full Text]

9. Lenfant C. Reflections on hypertension control rates: a message from the Director of the National Heart, Lung, and Blood Institute. Arch Intern Med. 2002; 162: 131–132.[Free Full Text]

10. Wilber JA, Barrow JG. Reducing elevated blood pressure: experience found in a community. Minn Med. 1969; 52: 97–99.

11. Hypertension Study Group. Guidelines for the detection, diagnosis and management of hypertensive populations. Circulation. 1971; 44: A263–A272.[Medline] [Order article via Infotrieve]

12. Hypertension Detection and Follow-up Program Cooperative Group. Persistence of reduction in blood pressure mortality of participants in the Hypertension Detection and Follow-up Program. JAMA. 1988; 259: 2113–2122.[Abstract/Free Full Text]

13. Krishnan I, Brennan LA Jr, Nobrega FT, Smoldt RK, Smutka LK, Labarthe DR, McEnaney JA, Hunt JC. The Mayo Three-Community Hypertension Control Program. II. Outcome of intervention in entire communities. Mayo Clin Proc. 1979; 54: 299–306.[Medline] [Order article via Infotrieve]

14. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwochuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM; for the ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North Am settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens. 2002; 4: 393–404.[CrossRef]

15. Staessen JA, Thijs L, Birkenhager WH Noncardiovascular illness as barrier to antihypertensive treatment. Hypertension. 2006; 255–256.

16. Wang PS, Avorn J, Brookhart MA, Mogun H, Schneeweiss S, Fischer MA, Glynn RJ. Effects of noncardiovascular comorbidities on antihypertensive use in elderly hypertensives. Hypertension. 2005; 46: 273–279.[Abstract/Free Full Text]

17. Weinehall L, Ohgren B, Persson M, Stegmayr B, Boman K, Hallmans G, Lindholm LH. High remaining risk in poorly treated hypertension: the ‘rule of halves’ still exists. J Hypertens. 2002; 20: 2081–2088.[CrossRef][Medline] [Order article via Infotrieve]

18. Burnier M. Blood pressure control and the implementation of guidelines in clinical practice: can we fill the gap? J Hypertens. 2002; 20: 1251–1253.[CrossRef][Medline] [Order article via Infotrieve]

19. Wielawaski IM. Improving chronic illness care. In: Isaacs SL, Knickman JR, eds. To Improve Health and Health Care. Vol X. San Francisco, Calif: Jossey-Bass; 1997: 49–80.

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21. Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, Wolf PA. The lifetime risk of stroke: estimates from the Framingham Study. Stroke. 2006; 37: 345–350.[Abstract/Free Full Text]

22. Kurth T, Logroscino G. Can we escape stroke and Alzheimer disease? Stroke. 2006; 37: 279–280.[Free Full Text]

23. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria JN, Vinters HV, Holtzman DM, Rosenberg GA, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006; 37: 2220–2241.[Abstract/Free Full Text]

24. Kuller LH, Lopez OL. Commentary: "Treatment of hypertension and prevention of dementia" by Olivier Hanon and Francoise Forette. Alzheimer Demen. 2005; 1: 38–40.


Related Article:

Reduced Medication Access: A Marker for Vulnerability in US Stroke Survivors
Deborah A. Levine, Catarina I. Kiefe, George Howard, Virginia J. Howard, O. Dale Williams, and Jeroan J. Allison
Stroke 2007 38: 1557-1564. [Abstract] [Full Text] [PDF]




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