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HYPERTENSON TREATMENT A SUCCESS STORY

HYPERTENSON TREATMENT A SUCCESS STORY. On Feb. 14, 2007 a 2-hour program on P.B.S. - Documentary: Heart Disease in America Excellent review of risk factor concepts Emphasis on sudden death - Gloom & Doom Little attention was paid to dramatic decreases in

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HYPERTENSON TREATMENT A SUCCESS STORY

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  1. HYPERTENSON TREATMENT A SUCCESS STORY

  2. On Feb. 14, 2007 a 2-hour program on P.B.S. - • Documentary: Heart Disease in America • Excellent review of risk factor concepts • Emphasis on sudden death - Gloom & Doom • Little attention was paid to dramatic decreases in • morbidity/mortality as a result of modification of • risk factors

  3. Many papers or lectures on Hypertension have been introduced as follows: “Hypertension treatment and control rates at goal BPS are unacceptably low. New methods for specific diagnoses and new novel treatments for hypertension must be found to improve outcome.”

  4. The literature tells us that—1-Prevalence of hypertension is increasing.2-Goal BP is being reached in fewer and fewer diabetics3-ESRD is increasing ----a discouraging picture???Are these just attempts to change approaches to management?

  5. JUST THE FACTS PLEASE

  6. Coronary Heart Disease Deaths: 1980-2000* 341,745 fewer deaths from CHD in 2000 (from 543/100,000 to 267/100,000) About 47% of benefit attributable to Rx post MI, revascularization for angina, etc 44% are probably result of changes in risk factors 24% cholesterol 20% BP 12% smoking 5% exercise These are partially offset by BMI & diabetes *N Eng J Med 2007;356:23

  7. Approximately 149,600 decrease in CHD deaths from 1980 to 2000 were attributable to changes in risk factors Decrease in SBP by only 5.1 mm Hg - 69,800 Decrease in Chol: 13 mg/dL - 82,800 Decrease in smoking prevalence by 11% - 39,900 N Eng J Med 2007;356:23

  8. AN HISTORIC JOURNEY WE SOMETIMES FORGET WHERE WE HAVE BEEN

  9. Comments about Hypertension-1931 “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” Hay, Brit Med J, 1931

  10. “Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it.” Paul Dudley White, 1931

  11. “It is well to emphasize that many cases of essential hypertension not only do not need any treatment but are much better off without it. Tice, Practice of Medicine, 1946

  12. 1946 Textbook - Diseases of the Heart, Friedberg “People with mild benign hypertension with levels up to 210/110 need not be treated” “There is a psychopathologic personality associated with hypertension”

  13. “Benign” Hypertension No. = 300; Av. age at time of diagnosis = 40 yrs; Av. follow up = 14 yrs Complications: Percent CHF 27% Cardiac enlargement 68% CVA 10% Proteinuria 14% “One is forced to conclude that..hypertension lasts longer than generally supposed - causing death most frequently in the fifties….” Perera.In Bell ET. Hypertension, Minnesota Press, 1957

  14. Treatment of Hypertension …Remedies suggested - “watermelon and cucumber seeds, mistletoe and garlic” - “red meat and sex were forbidden.” Page, late 1940s

  15. 1940s - 1950s Treatment of Hypertension: • Injection of typhoid bacilli • Kempner Rice Diet • Sympathectomy -Adrenalectomy • Ganglion and peripheral blocking agents

  16. Goodman and Gilman The Pharmacologic Basis of Therapeutics, 1941 10 mentions of hypertension in 1386 pages Therapy of Hypertension Barbiturates Thiocyanates Bismuth Bromides

  17. 1949 Dr. page, after trying pyrogen injections with some success in patients with malignant hypertension, stated that: “I need hardly say this is an unpleasant treatment but considering the danger of the disease to the life of the patient it is a small price to pay for the benefits.”

  18. HYPERTENSION TREATMENTS YearTreatment Non Drug Treatment 1922 Strict low-sodium diet 1929 Lumbar sympathectomy 1930s - 1950 Sedatives 1944 Kempner rice diet YearTreatment Early Antihypertensive Drugs 1930s Veratrum alkaloids 1940s Thiocyanates 1948 Antimalarials 1949 Reserpine Phenoxybenzamine 1950 Ganglion blockers 1951 Vasodilators Monamine oxidase inhibitors 1953 Central Alpha agonists

  19. The role of height, weight and use of alcohol or tobacco in hypertension In the opinion of the committee there is sufficient evidence to justify the con- clusion that none of these are concerned in the genesis of primary diastolic hypertension. Report of the AHA Committee on Hypertension, 1957

  20. HYPERTENSION TREATMENTS YearTreatment The Modern Era of Drug Therapy 1957 Chlorothiazide 1959 Peripheral sympathetic nerve blockers 1959 Aldosterone antagonists 1962 B-blockers YearTreatment 1964 Loop diuretics 1970 Alpha-beta blockers Calcium channel blockers 1974 Nitroprusside 1980 Angiotensin converting enzyme inhibitors 1990s Angiotensin II receptor blockers

  21. Early 1950s Preferred Therapy for Hypertension 1) A combination of rauwolfia and ansolysen 2) A combination of hydralazine and hexamethonium or 3) A combination of hydralazine, rauwolfia and ansolysen Moser M, Mattingly TW, Postgrad Med 1955

  22. FDR—A Classic Case of Untreated Hypertension Blood pressure(mm Hg) Complications Treatment Year PhenobarbitolLow-salt and low-fat dietMassagesDigitalis LVH CHF Renal failure CVAs April 12, 1945, cerebral hemorrhage. Death at 63. Bruen–HG. Ann Intern Med. 1970;72:579-591.

  23. Reversal of “Malignant Hypertension” With Antihypertensive Combinations* 280 Parenteral ganglion-blocking agents 29-year-old woman with malignant hypertension 260 240 220 200 BP(mm Hg) 180 160 140 120 100 80 60 LVHPapilledemaBUN, 26 mg/dL Fundi, grade 1BUN, 18 mg/dL Fundi, grade 1BUN, 15 mg/dLECG Normal BUN, 18 mg/dL Moved;lost to follow-up + * Therapy Hydrochlorothiazide 50 mg/day ^ Rauwolfia 50 mg/day Year 1954 55 56 57 58 59 60 61 62 63 64 65 66 78 * Hydralazine 200 mg/day; + Guanethidine 20-30 mg/day; ^ Mecamylamine 40-60 mg/day Moser M. The Treatment of Hypertension. Le Jacq, 2002.

  24. Response to Rauwolfia, Hydralazine, and Ganglion- Blocking Agents—With Addition of Thiazide* 42-year-old male with Stage 4 hypertension and LVH 270 BUN, 13.6 mg/dL BUN, 12.8 mg/dL BUN, 14.4 mg/dL 250 V5 ECG normal 200 Thiazide 150 mm Hg 100 V6 LVH * 1 50 2 3 4 5 6 Year ’53 ’55 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1 - Chlorothiazide 1 gm/d; 2 - 2 - Mecamylamine 75 mg/d; 3 - Hydrochlorothiazide 50 mg/d 4 - Hydralazine 600 mg/d; 5 - Guanethidine 10 mg/d; 6 - Rauwolfia 50 mg/d died suddenly at the age of 67 while chopping wood. Moser M. The Treatment of Hypertension. Le Jacq, 2002.

  25. Relationship Between GFR and Mortality in Renally Impaired HypertensivesTreated vs Untreated, 2-5 Year Follow-Up >100 19 10 14 3660-99 31 16 21 4340-59 5 20 10 100<40 7 43 9 100 Total 62 18 54 61 Treated Untreated Initial GFR(mL/min) No. Dead (%) No. Dead (%) Medications included hydralazine, rauwolfia drugs, and ganglion-blocking agents. Moyer JH et al. Am J Med. 1958:24:177-192.

  26. Treatment of Hypertension1960 Initialtreatment Subsequenttreatment Next step Next step Classification Moser M. The Treatment of Hypertension. Le Jacq, 2002.

  27. History of Hypertension Milestones • VA trial begins • VA trial demonstrates the • benefit of treating hypertension • National High Blood Pressure • Education program begins • 1977 JNC I

  28. When to Start Antihypertensive Drug Therapy1977 Diastolic BP (mm Hg) Antihypertensivetreatment Age 40-59 (y) Age >60 (y)* Age <40 (y) *At age >70, treatment not advisable except in severe cases.Simpson FO, 1977.

  29. JNC III JNC 7 JNC II JNC VI 1973 1976 1980 1984 1988 1993 1997 2003 >30 drugs Diuretics >50 drugs ACEI, CAs added >80 drugs 7 options NHBPEP STARTS >40 drugs diuretics, b-blockersAdded >25 drugs DBP 105Diuretics >60 drugs Diuretics/ b-blockers • 100 drugs • Diuretics Hypertension Guidelines: the JNCs and Drug Therapy JNC V JNC I Guidelines JNC IV Low-dose .

  30. Results of PLACEBO CONTROLLED TRIALS Effect of Antihypertensive Drug Treatment on CardiovascularEvents % Reduction in Events ** CHF Strokes LVH CVD CHD events Fatal/Non-fatal Deaths Fatal/Non-fatal *Combined results from 17 randomized placebo controlled treatment trials (48.000 subjects) Diuretic or Beta-blocker based **All differences are statistically significant Moser,J Am Coll Cardiol. 1996;27:1214-1218; Arch Intern Med 1993;S76-S71

  31. “It is generally forgotten that hyper- tensive vascular disease kills more people than cancer and AIDS com- bined. But hypertension is a dull disease to most of us, and its cure does not excite as that of cancer does.” Page, Modern Medicine 1988

  32. Example of Some Attitudes Regarding Treatment of Hypertension 1996 “The strategic targets for our attention in primary care should be patients with severe hypertension (diastolic pressures over 110 mm Hg), elderly patients, those with diabetes, patients who are at high risk for stroke, and those with known heart disease. Am Fam Phys 1996;53:2427

  33. SOME NEW DATA CONFIRM THAT WE MUST BE DOING SOMETHING RIGHT

  34. Hypertension in the Very Elderly – HYVET Study 3845 people >80 years of age Baseline BPs 160-189 or ISH >140 (mm Hg) 90-109 < 90 Low-dose diuretic (indapamide 1.5 mg SR) ACE-I (perindopril 2-4 mg/d) added, if necessary placebo-controlled Trial stopped early Strokes Mortality

  35. Status of Treatment & Control in Hypertensive Adults 1976 – 2007 Harris Poll BRFSS NHANES 1976-80 1988-91 1991-94 1999-2000 2003-2004 2007 2007 Percent Self Reported Specific Treatment31 55 54 59 65 73>90 Control* 10 29 27 34 37 ---- >60 *SBP <140 mm Hg and DBP <90 mm Hg

  36. A SUCCESS STORY INDEED

  37. Advice About the Early Treatment of Hypertension A little fire is quickly trodden out; which, being suffered, rivers cannot quench. Henry VIShakespeare

  38. “A few diseases may eventually predispose to early hypertension- syphilis, chronic lead poisoning, gout, and rheumatic fever. No evidence that foci of infections in teeth or tonsils responsible for hypertension.” Levine, Clinical Heart Disease, 1945

  39. Hypertension Treatment, 1946 “In a patient with mild benign hypertension, i.e., blood pressure <200/<100 mm Hg, there is no indication for use of hypotensive drugs. Continued observation is desirable and conservative treatment consisting of reassurance, mild sedatives, and weight reduction is indicated.” Friedberg. Diseases of Heart, 1946

  40. Antihypertensive Therapy 1970s - 1990s 1970s Alpha adrenergic inhibitors Alpha-Beta blockers Converting enzyme inhibitors 1980s Calcium channel blockers 1990s Angiotensin-II (AT1) receptor blockers

  41. “A significant proportion of men who exhibited a transient pressor response during examination for military service later developed sustained arterial hypertension.” (3.6 x greater than group without it) Levy, et al. JAMA 1947;135:77

  42. Physician Non Adherence or Inertia? Specific treatment and control rates in hypertensive patients have increased. BUT Approximately 30% of treated patients do not have their therapy changed, even when BPs remain elevated.

  43. Long-Term Blood Pressure Response to Chlorothiazide Therapy Average BP before addition of chlorothiazide Average BP after addition of chlorothiazide No. of cases Average BP change Chlorothiazide 15 174/108 159/100 –15/–8 Rauwolfia(+chlorothiazide) 39 184/112 166/98 –18/–14 Hydralazine Reserpine(+chlorothiazide) 17 170/102 156/94 –14/–8 Mecamylamine Hydralazine Reserpine (+chlorothiazide) 35 174/101 154/85 –20/–16 Total 106 Moser M et al. AMA Arch Intern Med. 1962;89:708-723.

  44. Hypertension Management Benefits and various modalities of treatment continue to be questioned. Are treatment trial data being overanalyzed? Are the debates truly based on science or on attempts to promote new devices or medical treatments?

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