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 Becomes First and Only ACE-Inhibitor Shown to Increase
 Survival in Symptomatic Heart Failure Patients
 WEST POINT, Pa., April 10 /PRNewswire/ -- Merck's (NYSE: MRK) ACE inhibitor Vasotec (enalapril maleate) has become the first and only drug in its class shown to increase survival in symptomatic heart failure patients.
 Vasotec received a broadened heart failure indication based on data from a major National Institutes of Health (NIH) study demonstrating that the drug significantly reduced deaths in all stages of symptomatic heart failure when compared with conventional therapy.
 Vasotec is indicated for the treatment of all stages of symptomatic heart failure usually in combination with conventional therapy, digitalis and diuretics. According to the revised prescribing information, "in these patients Vasotec improves symptoms, increases survival and decreases the frequency of hospitalization."
 In 1988, Vasotec was indicated as adjunctive therapy for patients who are not responding adequately to diuretics and digitalis. The drug had been demonstrated to improve survival for patients with severe heart failure.
 "The broadened heart failure indication for Vasotec is important news for physicians and patients," said Louis M. Sherwood, M.D., senior vice president, Medical and Scientific Affairs, U.S. Human Health. "The significance of the results of this and earlier mortality studies with Vasotec should redefine the treatment of heart failure, a tragic and debilitating disease for patients."
 Vasotec is a registered trademark of Merck & Co., Inc.
 Heart failure affects 2 to 3 million Americans, with about 400,000 new cases diagnosed each year. Fifty percent of patients diagnosed with heart failure die within five years. An estimated 2 million patients diagnosed with heart failure are hospitalized each year in the U.S. Heart failure is the most common cause of hospitalization in patients over 65.
 Results of NIH's SOLVD study Treatment Trial (Studies of Left Ventricular Dysfunction), which supported the broadened indication, demonstrated:
 Reduction in deaths:
 -- an 11 percent reduction in deaths from all causes, including heart failure, in the patients treated with Vasotec.
 -- a 17 percent reduction in deaths due to heart failure progression in patients taking Vasotec in addition to conventional therapy, including diuretics and digitalis, compared with patients taking placebo and conventional therapy.
 Reduction in hospitalizations:
 -- a 30 percent reduction in hospital admissions due to heart failure. The average cost for a heart failure hospitalization was about $6,375 in 1989, according to available Medicare data.
 The SOLVD Treatment Trial, a placebo-controlled trial reported in the August 1, 1991, issue of The New England Journal of Medicine, followed 2,569 patients with all degrees of symptomatic heart failure for up to 55 months.
 A second major mortality study supporting the broadened indication was the CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) trial involving 253 patients with severe heart failure.
 CONSENSUS patients treated with Vasotec in addition to diuretics and/or digitalis had 40 percent fewer deaths at six months -- and 31 percent fewer deaths at 12 months -- than patients taking diuretics and digitalis alone.
 Heart failure is a condition in which the heart does not pump enough blood to meet the body's needs. The resulting decrease in blood flow leads to a buildup of fluid in the lungs and body tissues. Symptoms include difficulty in breathing, fluid retention, fatigue, irregular heartbeats, and nausea. The beneficial effects of Vasotec in symptomatic heart failure appear to result primarily from the drug's ability to suppress production of the powerful vasoconstrictor angiotensin II. As plasma levels of angiotensin II fall, the resistance in blood vessels decreases, making it easier for the heart to pump blood into the arteries. A decrease in angiotensin II also results in a reduction in the body's production of aldosterone, a hormone that causes salt and water retention.
 Vasotec has been found to be generally well tolerated; for the most part, adverse experiences were mild and transient. Adverse experiences occurring in greater than two percent of heart failure patients treated with Vasotec include dizziness, hypotension, orthostatic effects, syncope, cough, diarrhea and chest pain. However, when used during the second and third trimesters of pregnancy, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
 The recommended starting dose of Vasotec for heart failure is 2.5 mg once or twice daily. The usual therapeutic dosing range is 5 to 20 mg daily given as a single dose or two divided doses; the majority of patient experience in clinical studies has been with twice daily dosing.
 Vasotec, introduced in January 1986 as a treatment for high blood pressure, is supplied in barrel-shaped tablets containing 2.5, 5, 10 or 20 milligrams of medication.
 Merck is a worldwide, research-intensive pharmaceutical company that discovers, develops, produces and markets human and animal health products and specialty chemicals. Merck has 37,000 employees, 17 research centers worldwide and manufacturing facilities in 17 countries. In 1992, the company plans to spend in excess of $1.1 billion on research and development.
 Complete prescribing information follows.
 Contact: Gary M. Bruell, 215-661-7485.
 Congestive heart failure in U.S.
 Scope of disease:
 -- Affects 2 to 3 million Americans, today (1)
 -- Approximately 400,000 newly diagnosed cases a year in U.S. (2)
 -- Affects about 1 percent of people in their 50s; rises progressively with age to affect about 10 percent of people in their 80s (Framingham Heart Study) (3)
 -- Women lag slightly behind men in incidence at all ages; male predominance attributed to higher rate of coronary heart disease (Framingham Heart Study data) (4)
 -- Resulted in over 35,000 deaths in 1988 (latest figures) (5)
 -- Six-year mortality rate in Framingham Heart Study: 82 percent for men; 67 percent for women (6)
 -- Two million heart failure patients hospitalized annually (7)
 -- Most common hospital discharge diagnosis in over-65 patients (8)
 What is heart failure? (9)
 Complex condition
 Clinical signs vary widely from mild to severe
 Causes are many and varied
 All forms of heart failure:
 -- Involve problem in heart's pumping action
 -- Are marked by inadequate movement of blood through the heart and the body's circulatory system
 How normal heart works (10)
 Beats between 70-80 times a minute (more than 100,000 times a day)
 Pumps about 2,000 gallons of blood a day
 Consists of two upper (entry) chambers -- the atria -- and two lower (output) chambers -- the ventricles; blood is pumped through chambers, aided by valves that direct blood flow when heart beats
 Normal blood flow through heart
 -- Right side of heart: Oxygen-poor blood from body enters right atrium ... passes into right ventricle ... is pumped out to lungs to pick up oxygen
 -- Left side of heart: Oxygen-rich blood from lungs enters left atrium ... passes into left ventricle (main pumping chamber of heart) ... is pumped out to body
 Underlying causes of heart failure (11)
 Structural abnormalities (congenital or acquired) that affect heart muscle, valves or peripheral and coronary vessels, placing increased burden on heart and leading over time to dysfunction of one or both ventricles
 May exist for years without symptoms until precipitating event occurs
 May include:
 -- Ischemia: loss of adequate of blood supply to heart muscle
 -- Caused by obstruction within coronary arteries
 -- Results in insufficient oxygen being supplied for heart muscle function (demand)
 -- High blood pressure (longstanding and uncontrolled): forces heart to pump against increased pressure in arteries
 -- Risk of heart failure increases progressively with severity of high blood pressure; (12)
 -- Risk of heart failure increased in individuals with isolated systolic high blood pressure (13)
 -- Valve damage (narrowed or leaky valves): forces heart to work harder than normal to move blood through chambers
 -- Diabetes: accelerates coronary artery disease and high blood pressure (14)
 Events that precipitate acute heart failure (15)
 Specific events that trigger acute heart failure with symptoms
 -- Heart attack
 -- Infection, particularly respiratory infections, and fever
 -- Arrhythmias: heartbeat irregularities
 -- Patient noncompliance: patients who are symptom-free while carefully adhering to treatment may incorrectly assume problem has been cured and reduce or discontinue therapy
 -- Anemia: forces heart to circulate oxygen-poor blood at more than normal rate to nourish organs and tissues
 -- Blood clots in lungs
 -- Environmental stress: Physical exertion, emotional crises, or extreme heat and humidity
 -- Use of drugs that depress heart function (e.g., alcohol, certain beta or calcium channel blockers) or increase salt/water retention (e.g., steroids, some nonsteroidal anti-inflammatory drugs)
 Compensating mechanisms (16)
 Body uses different adaptive mechanisms to compensate for deterioration of heart function and increase output of blood.
 May include:
 -- Action by central nervous system to strengthen force of heart's contractions
 -- Thickening of muscle wall of left ventricle to strengthen force of contraction
 -- Dilation of left ventricle to admit more blood from atrium
 Over time, compensating mechanisms may result in further deterioration of heart function
 Forms of heart failure (17)
 -- Most common
 -- Ventricle (generally, left ventricle) loses ability to contract properly; becomes unable to pump (eject) blood with sufficient force
 -- Heart becomes enlarged
 Diastolic (stiff heart syndrome)
 -- May involve either or both ventricles
 -- Ventricle loses elasticity, becomes unable to fill properly
 Progression of heart failure (18)
 Over time, dysfunction of either ventricle leads to:
 -- Buildup of pressure in atrial chamber and veins leading into ventricle; fluid is forced out of veins into surrounding tissue, resulting in edema of lungs and/or legs and ankles
 -- Reduced blood supply to vital organs, affecting function of vital organs: kidneys, liver and brain
 Stages of heart failure (19)
 Degrees of severity described by widely recognized New York Heart Association classification system
 Classification based on relation between certain symptoms (undue fatigue, shortness of breath, heart palpitation, and angina -- chest pain precipitated by insufficient supply of oxygen to heart muscle) and amount of physical activity that triggers them
 Class I: No limitation -- Patients can undertake ordinary physical activity without symptoms
 -- Class II: Slight limitation of physical activity -- Patients are comfortable at rest, but experience symptoms with ordinary physical activity
 -- Class III: Marked limitation of physical activity -- Patients are comfortable at rest, but experience symptoms with even mild activity
 -- Class IV: Inability to carry on any physical activity without discomfort -- Patients experience symptoms even at rest; may be awakened from sleep by shortness of breath (feeling of extreme suffocation, gasping for breath)
 Signs and symptoms of heart failure (20)
 Swollen legs or ankles
 Weight gain from fluid retention
 Shortness of breath
 Cool, pale hands and feet from reduced blood circulation
 Increased urination at night due to increased blood flow to kidneys when lying down
 Fatigue and weakness from insufficient supply of blood to skeletal muscles
 Confusion, memory impairment, anxiety, headache, insomnia caused by inadequate blood supply to brain
 Diagnosis (21)
 Based on:
 Patient history
 -- Shortness of breath
 -- Swelling of legs or ankles
 -- Crackling noises (rales) while breathing (heard by stethoscope)
 Chest x-ray to check for enlarged heart, indicating weakening of muscle
 Electrocardiogram (ECG) to detect previous heart attack
 Echocardiogram using sound waves to produce an image of heart and valves
 Measurement of ejection fraction (amount of blood expelled from the heart with each contraction)
 Three general goals (22)
 -- Address underlying cause (i.e., reduction of ischemia-caused damage to the ventricles, treatment of high blood pressure, correction of valve defects)
 -- Remove precipitating cause (i.e., control of arrhythmias, treatment of infections)
 -- Control heart failure state
 -- Improvement of heart's pumping performance
 -- Reduction of heart's workload
 -- Control of salt/water retention (principal cause of symptoms)
 Lifestyle changes: (23)
 -- Reduction of salt intake
 -- Reduction of weight in obese patients
 -- Reduction of strenuous physical activity; plus regular rest
 Medication: (24)
 -- Digitalis and diuretics traditional primary therapy. Digitalis used for heart failure for over 200 years.
 -- Digitalis: Increases force of heart's contraction; controls rate of heartbeat (25)
 -- Diuretics (thiazide, potassium-sparing and more potent loop diuretics): Eliminate excess salt and water to relieve edema; reduce volume of circulating blood to lower filling pressure in ventricles (26)
 -- Vasodilators (ACE inhibitors, hydralazine/nitrates): Dilate blood vessels, allowing blood to flow more easily and easing heart's workload; shown to reduce heart failure death rate (27)
 Surgery (heart transplant): (28)
 -- Approximately 2,000 performed annually in U.S.
 -- Five-year survival rate (as of 1990): from 73 to 84 percent, depending on use of immunosuppressive drugs
 -- Use limited by donor heart availability, financial constraints, growing incidence of heart failure in elderly patients
 1. 1991 Heart and Stroke Facts, American Heart Association, pp. 35-36.
 2. American Heart Association, 35
 3. William B. Kannel and Albert J. Belanger, Epidemiology of Heart Failure, American Heart Journal, March 1991, pp. 951.
 4. Kannel and Belanger, 951
 5. American Heart Association, 35
 6. Kannel and Belanger, 951
 7. Kannel and Belanger, 951
 8. Hal S. Hockfield and David J. Eskin, Congestive Heart Failure: An overview for the Internists, IM, Vol. 12, No. 3, March 1991, pp. 63.
 9. Eugene Braunwald, Heart Disease: A textbook of cardiovascular medicine, W. B. Saunders Company, 1988, pp. 471.
 10. American Heart Association, 6 & 7
 11. Braunwald, 474
 12. Kannel and Belanger, 954
 13. Kannel and Belanger, 954
 14. Kannel and Belanger, 955
 15. Braunwald, 474 & 475
 16. Eric R. Leibovitch, Congestive heart failure: A current overview, Geriatrics, Vol. 46, No.1, January 1991, p. 46
 17. Braunwald, 473 & 474
 18. Heart Failure, Harvard Heart Letter, December 1990, Vol. 1, No. 4.
 19. Braunwald, 479
 20. Braunwald, 475 & 478
 21. Harvard Heart Letter, 5
 22. Braunwald, 485 & 486
 23. Braunwald, 486, 488 & 489
 24. Braunwald, 489
 25. Braunwald, 490
 26. Braunwald, 516 & 508
 27. Braunwald, 66 & 522
 28. Firth, B.G., and Yancy, C.W., Survival in Congestive Heart Failure: Have We Made A Difference?, The American Journal of Medicine, January, 1990, Vol. 88, p 1-6N
 1. 1991 Heart and Stroke Facts, American Heart Association, pp. 35-36.
 2. Kannel, William B. and Albert J. Belanger, Epidemiology of heart failure, American Heart Journal, March 1991, pp. 951-957.
 3. Yusuf, Salim, Thom, Thomas, and Abbott, Robert D., Changes in hypertension treatment and in congestive heart failure mortality in the U.S., Hypertension, Supplement I, Vol 13, No 5, May 1989, pp. 74-79.
 4. Firth, B.G., and Yancy, C.W., Congestive Heart Failure, Dis. Mon., 1988, 34, pp. 467-536.
 5. Hockfield, Hal S. and David J. Eskin, Congestive Heart Failure: An overview for the Internists, IM, Vol 12, No. 3, March 1991, pp. 63-68.
 6. Heart Failure, Harvard Heart Letter, Lee and Goldman Editors, December 1990, Vol 1, No 4.
 7. Braunwald, Eugene, Clinical manifestations of heart failure, Heart Disease: A textbook of cardiovascular medicine, Braunwald, Ed., 1988, pp. 471-543.
 8. Leibovitch, Eric R., Congestive heart failure: A current overview, Geriatrics, Vol 46, No 1, January 1991, pp. 43-52.
 -0- 4/10/92
 /CONTACT: Gary M. Bruell (public affairs), 215-661-6681, or Gary L. Sender (investor relations), 908-594-6883, both of Merck/
 (MRK) CO: Merck & Co., Inc.; National Institutes of Health ST: Pennsylvania IN: MTC SU:

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