(Circulation. 1996;93:2205-2211.)
© 1996 American Heart Association, Inc.
Risk-Reduction Therapy: The Challenge to Change
Presented at the 68th Scientific Sessions of the American Heart Association November 13, 1995 Anaheim, California
 |
Introduction |
|---|
 Top Introduction References |
|---|
One of my great pleasures as President of the American Heart Association is addressing this distinguished group as we begin our 68th Scientific Sessions.
This year we return to Anaheim. For decades our children have come here to marvel at the wonders of Disneyland. From Frontierland to Tomorrowland, they have been inspired to understand the past and think about the future, and with that, to ponder the changes that challenge their lives.
Today, we in medicine certainly face great challenge and change. Molecular biology has expanded our knowledge and the frontiers of cardiovascular science. At the same time, our healthcare system faces revolutionary change. Clinicians worry about providing optimal care for their patients, and researchers wonder about continued funding for their projects. During the next 4 days, as we share our scientific discoveries and renew friendships, many conversations will turn to these changes and challenges occurring in medicine.
This morning I want to talk about challenge and change: the challenge to bring results of research to the bedside, and the need to change our treatment strategies to emphasize risk-reduction therapy for patients with cardiovascular disease. I'd like to begin by reviewing the American Heart Association and the strategies that have made it successful.
The American Heart Association has a history of translating research
findings into effective clinical therapies and public education
programs. Founded in 1924, the American Heart Association sprang from
recommendations of five clinical cardiologists: Drs Lewis Conner, James
B. Herrick, Joseph Sailer, Paul Dudley White, and Hugh
McCullough.1 Seventy years ago, in May 1925, the American
Heart Association held its first Scientific Sessions in Atlantic City.
That meeting's program2 shows a remarkable similarity to
the cardiovascular issues that confront us today. The
first four papers dealt with primary prevention, secondary prevention,
economic pressures, and concern about the future of
cardiovascular medicine (Fig 1
). At that
meeting, 200 people attended to hear presentations by 10
scientists. Compare that with this week's meeting, attended by an
estimated 33 000, who will hear and discuss more than 3800
abstracts.
|
For 24 years, the American Heart Association was a professional society. But in 1948 we expanded into a public, voluntary health organization. This increased our ability to develop effective preventive and educational programs for the public and raise funds for research. We have since contributed nearly $1.4 billion toward heart disease and stroke research. Our human element is equally impressive—more than 4 million medical, scientific, and nonmedical volunteers work with 14 national scientific councils and 53 affiliates throughout the United States.
We have grown since 1924, but the original strategies and principles remain the same. Research, prevention, and education play fundamental roles in reducing society's burden from heart disease and stroke. These enterprises enabled us to make great strides in treating, and in many cases, preventing, one form of heart disease—rheumatic heart disease.
Now we are confronted with an epidemic of atherosclerotic cardiovascular disease. In the United States coronary heart disease claims the lives of an estimated 500 000 men and women each year. Stroke kills more than 140 000.3 Taken together, cardiovascular diseases kill Americans at the rate of one every 34 seconds. In the short time I will speak today, cardiovascular disease will claim 40 lives in this country. And when we adjourn this conference, it will have killed nearly 10 000 and disabled many more.
The prevalence of coronary heart disease and congestive heart
failure has increased during the last decade. During the same period,
technical advances in diagnosis, imaging, medical therapy, and
interventional procedures have vastly improved care for heart disease
and stroke patients. But we have quite literally paid a price for these
technical advances. Increasing costs have led to major changes in
healthcare delivery. Cost shifting has occurred to provide care for
growing numbers of indigent patients. The cost of treating patients
with cardiovascular disease in the United States
continues to spiral upward, from $109 billion in 1992 to an estimated
$138 billion for the year 1995.3 Most of these dollars,
$88 billion, will pay for hospital and related services (Table 1).
|
A major factor in these rising hospital costs is the increasing number of coronary bypass surgeries and coronary angioplasties. Adding to the strain is the annual treatment of nearly 1 million people with acute myocardial infarction. To understand the challenge we face we must contrast these enormous costs with the relatively small amount of money now spent on medical treatment and lifestyle changes for heart disease and stroke patients. For every dollar we spend on cardiovascular disease in this country, only 6 cents is spent on medical therapy and on reinforcing healthy lifestyles.3
The increased prevalence of cardiovascular disease has not been limited to the United States. Increased cardiovascular mortality has been reported in Eastern Europe.4 In lower socioeconomic groups, there is an increased prevalence similar to that observed in the United States. In Finland, men of low socioeconomic status have significantly more carotid arterial obstructions than their more highly educated or wealthier cohorts.5
The increased prevalence of cardiovascular disease, despite refinements in technology, points to a need for further research. Yet today, funding for biomedical research and graduate medical education has become increasingly restricted. It's as though we had forgotten that today's clinical treatments are available to us only because of past investments in biomedical research.
In 1984 Drs Brown and Goldstein received the American Heart Association's Research Achievement Award. One year later, they were awarded the Nobel Prize for their work on LDL receptors and cholesterol metabolism. They were supported by grants from the American Heart Association and the National Heart, Lung, and Blood Institute. Today, a decade after receiving the Nobel Prize, their research, and that of hundreds of other investigators, provides new insight into the pathophysiology of atherosclerosis. Such investigations also guide us toward appropriate treatment strategies for the nearly 13 million US patients with coronary heart disease. These advances in our basic understanding of the atherosclerotic process will be reviewed in greater detail in this morning's Conner Lecture by one who has been at the forefront of much of this work, Dr Daniel Steinberg.
During this period of intense basic research we have refined techniques in cardiac surgery and interventional cardiology. These advances focus primarily on relieving coronary obstruction. But the new understandings from vascular biology and molecular biology now suggest that therapy must address the entire atherosclerotic process, not just severe obstructions.
Angiographic studies on patients before myocardial infarction show that
the majority of subsequent events involve sites with <70%
obstruction6 (Fig 2). Earlier this year, an AHA
task force published a review of atherosclerotic lesions,7
emphasizing the importance of type IV and Va lesions in acute
coronary syndromes. These high-risk lesions initially
expand outward and are usually asymptomatic, with
minimal obstruction. They are less frequently associated with
collaterals and more often the cause of acute coronary
syndromes.8 Histologically they show a
thin cap and large subcapsular lipid pool. Plaque rupture usually
occurs at the margin and is related to complex factors that include
inflammation, secondary suppression of collagen synthesis, and
stimulation of collagen breakdown that is prompted to ulceration by a
series of triggering events.9 10
|
Therapy that lowers cholesterol by 20% results in a
significant decrease in cardiovascular events within 1
to 2 years. However, the changes in stenosis associated with
these impressive clinical events are quite small, in the order of 1%
to 2%.11 (Table 2). Although treated
groups show more regression and less progression of disease, this does
not explain the improved outcome. Stabilizing high-risk plaques
appears to account for the impressive reduction in
cardiovascular events,11 12 13 and treatment
of certain risk factors also tends to correct the abnormal
endothelial changes that occur early in the course of
atherosclerosis. Lowering of LDL, estrogen replacement
therapy, and smoking cessation all act to improve
endothelial function. Thus, the major effects of
lipid-lowering therapy appear related to stabilization of
high-risk plaques and improvement in abnormal
endothelial function.
|
Early trials of lipid-lowering therapy demonstrated
cardiovascular benefit but were not of sufficient power
to show a reduction in total mortality. However, the Scandinavian 4S
study,14 reported last year at this meeting, resolved this
issue. It showed a striking 30% reduction in total mortality and a
42% reduction in coronary mortality in more than 4000
coronary heart disease patients randomized to
lipid-lowering therapy or placebo for an average of 5.4 years
(Table 3). Especially important was a 37% reduction
in revascularization procedures and a 34%
reduction in hospital days. Importantly, these improvements began
early, only 1 to 2 years after starting therapy.
|
Further benefits of lipid-lowering therapy have been reported in
studies measuring carotid artery intima/media thickness by ultrasound.
The ACAPS investigators found in patients with no clinically manifest
cardiovascular disease that lipid lowering led to a
decrease in cardiovascular events and
mortality.15 The changes in events paralleled
changes in intima/media thickness (Fig 3). This suggests a
role for lipid-lowering therapy in all patients with
peripheral and cardiac atherosclerotic vascular
disease.
|
There are other risk-reduction therapies with similar ability to
improve the outlook for our patients with
cardiovascular disease. ACE
(angiotensin-converting enzyme) inhibitor
therapy after myocardial infarction for symptomatic and
asymptomatic left ventricular failure
reduces total mortality, cardiovascular mortality,
recurrent hospitalizations, and recurrent myocardial infarctions (Table 4).16 17 These results are similar to
those seen with lipid-lowering therapy. The SOLVD trials also
emphasized the increased mortality from subsequent myocardial
infarction and unstable angina in patients with impaired left
ventricular function.18 In both the SOLVD and
SAVE trials, ACE inhibitor therapy reduced acute
ischemic events possibly secondary to vascular
remodeling.17 19 The SAVE study revealed a decreased need
for revascularization procedures for those treated
with ACE inhibitors.19
|
Unfortunately, most patients in the healthcare system do not receive comprehensive risk-reduction therapies. In spite of all we've learned from the past decade's research in vascular and molecular biology, in spite of vast sums spent on randomized clinical trials showing a decrease in cardiovascular events: in spite of all this, most patients still do not receive comprehensive risk-reduction therapies after myocardial infarction or revascularization procedures.
Recently, a study of patients with known coronary artery
disease revealed that less than one in five with elevated
cholesterol received lipid-lowering therapy; 2 years
later, nearly two of three still were not treated with
lipid-lowering agents.20 In the CCP pilot study
database evaluating therapy after myocardial infarction, only 28% had
documented counseling on smoking cessation; <50% of eligible
candidates received ß-blocker therapy, and >40% did not receive
ACE inhibitors. Only aspirin therapy at 77% approached an
almost acceptable level of implementation21 (Fig 4).
|
The reasons these risk-reduction therapies are not fully implemented include failure of physicians to agree on strategies, failure of healthcare providers to implement risk-reduction therapies, poor patient adherence to prescribed therapies, and lack of payment for risk-reduction therapies. All our hard-won knowledge, all the tools we have developed have little value unless we can resolve these issues. And we must begin.
As a first step, an AHA panel published in July 1995 a set of
comprehensive risk-reduction strategies that can extend overall
survival, improve quality of life, decrease the need for
revascularization, and reduce subsequent
cardiovascular events in patients with coronary
heart and vascular disease.22 (Fig 5). These
consensus strategies are endorsed by the American College of
Cardiology. Congruent efforts to reduce risk with
optimal medical therapies have been initiated jointly by three major
European societies.23 Thus, the
cardiovascular communities of the United States and
Europe are poised to move forward with major risk-reduction
strategies.
|
The AHA's recommendations emphasize lifestyle modification and medical
therapy in treating all patients with coronary and vascular
disease. One such strategy is smoking cessation, which could reduce
mortality by more than 40%. While attending the European Congress of
Cardiology in Amsterdam last summer, I was impressed
with the painting Skull with a Burning Cigarette by van Gogh
(Fig 6). While it is not one of his better-known works,
it certainly brings the dangers of tobacco to our attention: sort of a
19th century expressionist version of the Surgeon General's warning.
The danger of tobacco use has long been a concern of the American Heart
Association. But we believe smoking-cessation programs must be
accompanied by efforts in primary prevention. In the time we spend this
week discussing these issues, 12 000 children will start smoking in
this country. In patients under 50 years of age, myocardial infarction
occurs five times more frequently in smokers. Cigarettes are
responsible for 80% of the cardiovascular mortality in
patients younger than 50. Only 5% of the world's population of
women live in the United States, but 50% of the tobacco-related
deaths in women occur in our country.3 24 25 26 Smoking
cessation is difficult. Many agree effective programs must target
youth. Later this morning, Dr David Kessler, Commissioner of the Food
and Drug Administration, will share with us the critical need for
better control of tobacco use.
|
We have discussed the importance of risk-reduction therapy to
improve lipid abnormalities, the benefits of ACE inhibitors
after myocardial infarction, and smoking cessation. Other strategies
exist as well. Antiplatelet agents and anticoagulants reduce
mortality in patients with established cardiovascular
disease.27 28 Aspirin and other antiplatelet
agents are of primary importance in treating and preventing acute
ischemic syndromes. A recent report in Circulation
demonstrated a 72% reduction in the odds ratio for myocardial
infarction in patients taking aspirin.29 ß-Blocker
therapy can reduce mortality by at least 20%, yet results from the
recent cooperative cardiovascular program indicate that
<50% of eligible patients receive ß-blocker therapy at time of
discharge.21 30 Control of hypertension remains a
significant problem in the US. It affects 60 million Americans, yet
79% of hypertensive patients do not receive adequate treatment,
leaving many to suffer needlessly from stroke and heart
disease.3 Physical activity and weight management are
important, cost-effective lifestyle changes that can reduce
cardiovascular risk.
Developing consensus on these strategies (Fig 5
) was only the first
step. As a second step, the AHA is distributing this consensus
statement22 to more than 200 000 cardiologists, primary
care physicians, nurses, and healthcare providers. In our annual
mailings, we are sending letters to more than 42 million, educating
them on risk-reduction strategies for
cardiovascular disease, creating a broad awareness.
I noted earlier that the lack of patient adherence to medication and lifestyle changes is a barrier to effective risk-reduction therapy. Nearly 50% of those receiving risk-reduction therapy stop within 1 year.31 32 33 34 An AHA task force is evaluating and recommending programs to improve patient adherence and compliance with medical therapy and lifestyle modification.
Although the cardiovascular physician must play a
leadership role in risk-reduction efforts, I believe success will
depend upon a team approach involving nurses and other healthcare
providers. Recent work from the Stanford Cardiac Rehabilitation
MULTIFIT program revealed significant improvement in risk-reduction
therapies with a nurse-managed program35 (Table 5). Most agree our healthcare delivery system must
change to include greater involvement by nurses and other healthcare
providers if we expect risk-reduction efforts to be successful.
|
Finally, financial support by third-party payers for these therapies is essential. In July members from major managed-care groups from across the country met in Dallas to explore joint activities with the American Heart Association to expand the use of risk-reduction therapies. This group will meet during the next year to further define efforts ensuring implementation. To complement these efforts, a working group is reviewing the economic impact of multiple-risk treatments. To date, these strategies have been evaluated as single therapies with favorable results.36 At these sessions, a number of presentations review actual cost data for risk-reduction therapies.37 38 39 In a plenary session this afternoon, Dr Lee Goldman will further address the economic impact of risk-reduction therapies.
It is clear we have our work cut out for us. But it's fair to remind ourselves we have come a long way, as well. When the American Heart Association was founded there were hospitals throughout the country that specialized in caring for the many patients with rheumatic heart disease. Today these hospitals no longer exist, largely because of research results and applied preventive efforts. We can achieve similar results with atherosclerotic vascular disease. But success will require support from the entire cardiovascular community. Interventional cardiologists and cardiac surgeons can help by emphasizing the importance of these therapies to their patients. The widespread use of risk-reduction therapies can improve patient care and outcomes.
Many years ago, while performing lipoprotein research for my Yale thesis with Dr Robert Levy at the NIH, I decided to pursue a career in cardiovascular medicine. Fueled by youthful enthusiasm, I was convinced that some day therapy would be available to alter the course of atherosclerotic cardiovascular disease. At that time I encountered the fascinating first report of xanthelasma by Addison and Gull, published in 1851.40 Interestingly, the patient was a woman. Her image reminds us that we live in an era in which cardiovascular disease claims the lives of more women than men in our country each year.
We do have a long way to go and much work to do. We are delving into the genetic mysteries of human diseases. At least 56 sites have been identified on the human genome that relate to cardiovascular disease. Understanding the genetic aspects of cardiovascular disease will further advance our therapies, just as Brown and Goldstein's research did nearly a decade ago. And exciting opportunities lie ahead in clinical research. Dr Myron Weisfeldt is leading an AHA effort to understand the role of automatic external defibrillators in reducing sudden cardiac death.
Unfortunately, government funding for biomedical research is jeopardized. Throughout this meeting we invite you to visit the American Heart Association booth and learn how you can help with the efforts to increase federal research funding. We must continue to show our policy makers that basic research leads to clinical advances and cost-effective treatments. If we expect Congress to fund further biomedical research we must rigorously apply the results of our recent research efforts to patient treatment. Our strongest testimony to the value of continued research support is applying basic scientific advances to daily medical practice.
Like the now-empty hospitals for rheumatic heart disease, the prognosis for patients with atherosclerotic disease can be dramatically improved. How might this happen? It will involve change. It will mean using risk-reduction therapies broadly in the treatment of patients with cardiovascular disease. It will require expanded healthcare provider teams, new cooperative efforts with managed care and the biopharmaceutical industry, and, possibly, international collaborative efforts. But it can only happen if we resolve to make it happen.
The founders of the American Heart Association were clinicians concerned about patient care. They emphasized the need for research, prevention, and education. These principles are as important to our success today as when the AHA was founded. In 1972, nearly 50 years after the founding of the American Heart Association, Dr Paul Dudley White, a founder and past president, reemphasized the need for this organization to vigorously support preventive efforts.41
Today, more than two decades later, our calling is the same. I'd ask you to share my hope that when we gather two decades from now in the year 2015, we will be able to say we have advanced the cause of risk-reduction therapy. Rarely has cardiovascular medicine faced greater challenges. Rarely have our patients expected more of us. But never have we had such tools to make people well. Never have we had such potential to do the work for which this organization was created. The strongest testimony to the value of our research is its benefit to patient care. We have seen great strides in acute care and intervention for cardiovascular disease patients. Now, risk-reduction therapy for these patients is strongly supported by sound research. It holds tremendous promise. It is now time to make good on that promise.
|
Footnotes |
|---|
Requests for reprints should be sent to the American Heart Association, Office of Science and Medicine, 7272 Greenville Ave, Dallas, TX 75231-4596.
|
References |
|---|
|
TopIntroductionReferences |
|---|
-
Moore WW. Fighting for Life: The
Story of the American Heart Association, 1911-1975. Dallas, Tex:
American Heart Association; 1983.
-
The American Heart Association Bulletin.
November 1925;1(2).
-
Heart and Stroke Facts: 1995 Statistical
Supplement. Dallas, Tex: American Heart Association; 1995.
-
Pyorala K. Changing coronary heart
disease trends in Europe: implications for prevention: Geoffrey Rose
Memorial Lecture. Presented at the European Society of
Cardiology Meeting; August 1995; Amsterdam,
Netherlands.
-
Lynch J, Kaplan GA, Salonen R, Cohen RD, Salonen
JT. Socioeconomic status and carotid
atherosclerosis.
Circulation. 1995;92:1786-1792.
[Abstract/Free Full Text]
-
Falk E, Shah PK, Fuster V.
Coronary plaque disruption.
Circulation. 1995;92:657-671.
[Free Full Text]
-
Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov
S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler
RW. A definition of advanced types of atherosclerotic lesions
and a histological classification of
atherosclerosis: a report from the Committee on
Vascular Lesions of the Council on
Arteriosclerosis, American Heart
Association. Circulation. 1995;92:1355-1374.
[Abstract/Free Full Text]
-
Fuster V, Lewis A. Connor Memorial Lecture:
mechanisms leading to myocardial infarction: insights from studies of
vascular biology. Circulation. 1994;90:2126-2146.
[Abstract/Free Full Text]
-
Libby P. Molecular bases of the acute
coronary syndromes. Circulation. 1995;91:2844-2850.
[Free Full Text]
-
Muller JE, Abela GS, Nesto RW, Tofler GH.
Triggers, acute risk factors and vulnerable plaques: the lexicon of a
new frontier. J Am Coll Cardiol.. 1994;23:809-813. [Abstract]
-
Levine GN, Keaney JF Jr, Vita JA.
Cholesterol reduction in cardiovascular
disease: clinical benefits and possible mechanisms.
N Engl J Med.. 1995;332:512-521.
[Free Full Text]
-
Philbin EF, Pearson TA. How does
lipid-lowering therapy rapidly reduce ischemic
events? J Myocard Ischemia.. 1994;6:13-18.
-
Pitt B, Mancini GBJ, Ellis SG, Rosman HS, Park J-S,
McGovern ME, for the PLAC I investigators. Pravastatin
limitation of atherosclerosis in the coronary
arteries (PLAC I): reduction in atherosclerosis
progression and clinical events. J Am Coll
Cardiol.. 1995;26:1133-1139. [Abstract]
-
Randomised trial of cholesterol lowering in
4444 patients with coronary heart disease: the Scandinavian
Simvastatin Survival Study (4S). Lancet.. 1994;344:1383-1389. [Medline]
[Order article via Infotrieve]
-
Furberg CD, Adams HP Jr, Applegate WB, Byington RP,
Espeland MA, Hartwell T, Hunninghake DB, Lefkowitz DS, Probstfield
J, Riley WA, Young B. Effect of lovastatin on early
carotid atherosclerosis and
cardiovascular events: Asymptomatic Carotid
Artery Progression Study (ACAPS) Research Group.
Circulation. 1994;90:1679-1687.
[Abstract/Free Full Text]
-
Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr,
Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, Klein M, Lamas
GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH,
Hawkins CM, on behalf of the SAVE Investigators. Effect of captopril on
mortality and morbidity in patients with left ventricular
dysfunction after myocardial infarction: results of the survival and
ventricular enlargement trial. N Engl
J Med.. 1992;327:669-677. [Abstract]
-
Lonn EM, Yusuf S, Jha P, Montague TJ, Teo KK, Benedict
CR, Pitt B. Emerging role of
angiotensin-converting enzyme inhibitors in
cardiac and vascular protection.
Circulation. 1994;90:2056-2069.
[Free Full Text]
-
Yusuf S, Pepine CJ, Garces C, Pouleur H, Salem D,
Kostis J, Benedict C, Rousseau M, Bourassa M, Pitt B. Effect of
enalapril on myocardial infarction and unstable angina in patients with
low ejection fractions. Lancet.. 1992;340:1173-1178. [Medline]
[Order article via Infotrieve]
-
Rutherford JD, Pfeffer MA, Moye LA, Davis BR, Flaker
GC, Kowey PR, Lamas GA, Miller HS, Packer M, Rouleau JL, Braunwald
E. Effects of captopril on ischemic events after
myocardial infarction: results of the Survival and
Ventricular Enlargement trial.
Circulation. 1994;90:1731-1738.
[Abstract/Free Full Text]
-
Cohen MV, Byrne MJ, Levine B, Gutowski T, Adelson
R. Low rate of treatment of
hypercholesterolemia by cardiologists in
patients with suspected and proven coronary artery
disease. Circulation. 1991;83:1294-1304.
[Abstract/Free Full Text]
-
Ellerbeck EF, Jencks SF, Radford MJ, Kresowik TF, Craig
AS, Gold JA, Krumholz HM, Vogel RA. Quality of care for Medicare
patients with acute myocardial infarction: a four-state pilot study
from the Cooperative Cardiovascular
Project. JAMA.. 1995;273:1509-1514. [Abstract]
-
Smith SC Jr, Blair SN, Criqui MH, Fletcher GF, Fuster
V, Gersh BJ, Gotto AM, Gould KL, Greenland P, Grundy SM, Hill MN,
Hlatky MA, Houston-Miller N, Krauss RM, LaRosa J, Ockene IS, Oparil S,
Pearson TA, Rapaport E, Starke RD. Preventing heart attack and
death in patients with coronary disease.
Circulation. 1995;92:2-4.
-
Pyorala K, De Backer G, Graham I, Poole-Wilson P, Wood
D. Prevention of coronary heart disease in clinical
practice: recommendations of the Task Force of the European Society of
Cardiology, European Atherosclerosis
Society and European Society of Hypertension. Eur Heart
J.. 1994;15:1300-1331.
[Free Full Text]
-
Parish S, Collins R, Peto R, Youngman L, Barton J,
Jayne K, Clarke R, Appleby P, Lyon V, Cederholm-Williams S, Marshall J,
Sleight P, for the ISIS Collaborators. Cigarette smoking, tar yields,
and non-fatal myocardial infarction: 14,000 cases and 32,000
controls in the United Kingdom. BMJ.. 1995;311:471-477.
[Abstract/Free Full Text]
-
Mortality from Smoking in Developed Countries,
1950-2000: Indirect Estimates from National Vital Statistics. New
York, NY: Oxford University Press; 1994:A-74.
-
Bartecchi CE, MacKenzie TD, Schrier RW. The
human costs of tobacco use. N Engl J
Med.. 1994;330:907-912,975-980.
[Free Full Text]
-
Secondary prevention of vascular disease by prolonged
antiplatelet treatment: Antiplatelet Trialists'
Collaboration. Br Med J (Clin Res Ed).. 1988;296:320-331.
-
Smith P, Arnesen H, Holme I. The effect of
warfarin on mortality and reinfarction after myocardial
infarction. N Engl J Med.. 1990;323:147-152. [Abstract]
-
Garcia-Dorado D, Theroux P, Tornos P, Sambola A,
Oliveras J, Santos M, Soler JS. Previous aspirin use may
attenuate the severity of the manifestation of acute ischemic
syndromes. Circulation. 1995;92:1743-1748.
[Abstract/Free Full Text]
-
Yusuf S, Peto R, Lewis J, Collins R, Sleight P.
Beta blockade during and after myocardial infarction: an overview of
the randomized trials. Prog Cardiovasc Dis.. 1985;27:335-371. [Medline]
[Order article via Infotrieve]
-
Andrade SE, Walker AM, Gottlieb LK, Hollenberg NK,
Testa MA, Saperia GM, Platt R. Discontinuation of
antihyperlipidemic drugs: do rates reported in
clinical trials reflect rates in primary care settings?
N Engl J Med.. 1995;332:1125-1131.
[Abstract/Free Full Text]
-
Patient Compliance: Lipid Lowering Agents TOP Study.
Merck & Co, Inc; 1992.
-
Gillum RF, Neutra RR, Stason WB, Solomon HS.
Determinants of dropout rate among hypertensive patients in an urban
clinic. J Community Health.. 1979;5:94-100. [Medline]
[Order article via Infotrieve]
-
Wirebaugh SR, Whitney EJ. Long-term
compliance with lipid-lowering therapy. Pharmacol
Ther.. 1993;18:559-71.
-
DeBusk RF, Miller NH, Superko HR, Dennis CA, Thomas
RJ, Lew HT, Berger WE III, Heller RS, Rompf J, Gee D, Kraemer HC,
Bandura A, Ghandour G, Clark M, Shah RV, Fisher L, Taylor CB. A
case-management system for coronary risk factor
modification after acute myocardial infarction. Ann
Intern Med.. 1994;120:721-729.
[Abstract/Free Full Text]
-
Tsevat J, Duke D, Goldman L, Pfeffer MA, Lamas GA,
Soukup JR, Kuntz KM, Lee TH. Cost effectiveness of captopril
therapy after myocardial infarction. J Am Coll
Cardiol.. 1995;26:914-919. [Abstract]
-
Gaspoz JM, Goldman P, Williams L, Weinstein M, Goldman
L. Cost-effectiveness of aspirin in secondary prevention of
coronary heart disease.
Circulation. 1995;92(suppl I):I-47. Abstract.
-
Glick H, Cook J, Pitt B, Kinosian B, Bourassa M,
Pouleur H, Gerth W. The cost and benefits of enalapril therapy
in post-MI patients with asymptomatic left
ventricular dysfunction.
Circulation. 1995;92(suppl I):I-510. Abstract.
-
Schwartz JS, Kjekshus J, Pedersen TR. Impact of
cholesterol lowering on resource use and cost among
patients with coronary heart disease (CHD): results from
4S. Circulation. 1995;92(suppl I):I-510.
Abstract.
-
Addison T, Gull W. On a certain affection of the
skin Vitiligoidea –
. Plana, ß. Tuberosa.
Guy's Hospital Gazette.. 1851;7:265-276.
-
White PD. The tardy growth of preventive
cardiology. Am J Cardiol.. 1972;29:886-888.[Medline]
[Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  K M J Douglas, A V Pace, G J Treharne, A Saratzis, P Nightingale, N Erb, M J Banks, and G D Kitas Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome Ann Rheum Dis, March 1, 2006; 65(3): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Smith Jr Evidence-Based Medicine: Making the Grade: Miles to Go Before We Sleep Circulation, January 17, 2006; 113(2): 178 - 179. [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Strauss, M. Dunphy, and N. Tokita Imaging the Vulnerable Plaque: A Scintillating Light at the End of the Tunnel? J. Nucl. Med., July 1, 2004; 45(7): 1106 - 1107. [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Kensey Rheology: An Overlooked Component of Vascular Disease Clinical and Applied Thrombosis/Hemostasis, April 1, 2003; 9(2): 93 - 99. [PDF]
|
|
|
|
 |
|
 E. J. Benjamin, S. C. Smith Jr, R. S. Cooper, M. N. Hill, and R. V. Luepker Task Force #1--magnitude of the prevention problem: opportunities and challenges J. Am. Coll. Cardiol., August 21, 2002; 40(4): 588 - 603. [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Lacy, D.-C. Suh, J. A. Barone, M. Bueno, D. Moylan, C. Swartz, R. V. Kudipudi, and J. B. Kostis Impact of a Targeted Intervention on Lipid-Lowering Therapy in Patients With Coronary Artery Disease in the Hospital Setting Arch Intern Med, February 25, 2002; 162(4): 468 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. O. Akosah, R. M. Cerniglia, P. Havlik, and A. Schaper Myocardial Infarction in Young Adults With Low-Density Lipoprotein Cholesterol Levels <= 100 mg/dL : Clinical Profile and 1-Year Outcomes Chest, December 1, 2001; 120(6): 1953 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Corsini Reviews: Fluvastatin: Effects Beyond Cholesterol Lowering Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(3): 161 - 175. [Abstract] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||