Controversies in Hypertension and Are We Winning the Battle with Heart Disease? Stephen Battista MD

Transcription

1 Controversies in Hypertension and Are We Winning the Battle with Heart Disease? Stephen Battista MD

2 No Disclosures

3 Deaths per 100,000 UNITED STATES DEATHS RATES Heart Disease Cancer 350 Tuberculosis Diarrheal Disease 300 Pneumonia

4 PERCENTAGES OF CARDIOVASCULAR DISEASE DEATHS

5 HEART DISEASE: THE BATTLE BEGINS 1948 The National Heart Institute is created with an initial appropriation of $500, The Framingham Study begins The first report identifies risk factors Hypertension Hypercholesterolemia Cigarette smoking

6 HYPERTENSION 1928 The Mayo Clinic described malignant hypertension. Very high BP with severe retinopathy, and adequate renal function which usually resulted in death within the year from strokes, heart failure or kidney failure. Benign essential hypertension was thought to be just that. the greatest danger to a man with high blood pressure lies in it s discovery, because some fool is certain to try to reduce it John Hay Professor of Medicine at Liverpool University. hypertension may be an important compensatory mechanism which should not be tampered with. Paul Dudley White textbook Charles Friedberg s Diseases of the Heart people with mild hypertension (up to 210/100) need not be treated. Chlorothiazide was the first well tolerated oral medication in 1958

7 HYPERTENSION Clinical trials have shown that treatment of hypertension reduces the risk of cardiovascular outcomes including CVA 35-40% Myocardial Infarction 15-25% Congestive Heart Failure up to 64%

8 What is the Ideal Blood Pressure? /75

9 JNC 7 (2003) Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Recommended treating type 2 diabetics to a systolic BP goal of <130 Prehypertension BP /80-89 Pts >50yo Systolic BP is more important than diastolic Thiazide type diuretics favored

10 ACCORD TRIAL-BP The Action to Control Cardiovascular Risk in Diabetics Blood Pressure ACCORD (Jan October 2005 recruitment) 10,251 total pts high vs. low intensity diabetes control 5518 pts. ACCORD Lipid Trial simva vs simva + fenofibrate 4733 pts. ACCORD BP Trial systolic <140 vs <120 High Risk Pts HbA1c > 7.5 Over 40 years of age with CVD Or over 55yo (<79) with Atherosclerosis, albuminuria, LVH, or two additional risk factors (dyslipidemia, htn, smoking, or obesity) Exclusion. BMI >45, Cr >1.5, serious illness ACCORD BP BP < 130 and >180, > 3 antihtn meds, 24 hr proteinuria > 1 gram.

11 ACCORD TRIAL-BP The Action to Control Cardiovascular Risk in Diabetics Blood Pressure Results (5 years) Sys BP vs (average 14.2) # of meds 3.4 vs. 2.1 Primary End Point -Composite of nonfatal MI s, nonfatal CVA s, or death from CV cause. 1.87% vs HR P=0.20 Only total stroke and nonfatal stroke achieved statistical significance

12 JNC 8 (2014) Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Pts >60yo Goal <150/90* If in treating pts over 60, systolic BP drops below 140 sys and pt tolerates it without adverse effects on health and quality of life, treatment does not need to be adjusted. All Pts >30 and <60yo Goal <140/90 Nonblack pts favors ACEI, ARB, Ca channel blocker, or thiazide type diuretic* Black pts favor Ca channel blockers or thiazide diuretics* * Supported by RCT

13 Sprint Trial Compare safety and effect of intensive blood pressure control. (systolic BP < 140 vs. <120) 9,361 pts 5 yr follow up Age >50 plus one risk factor for CV disease Exclusion inc DM, CVA, ACS w/i 3 mos, symptomatic CHF w/i 6 mos, EF<35%.

14 Sprint Trial Stopped Early (3 years and 3 months) Results Decrease in CHF 38% 1.3% vs 2.1% p=0.002 Decrease in CV mortality 43%.8% vs. 1.4% p= Decrease in All Mortality 27% 3.3% vs 4.5% p= Decrease in Myocardial Infarctions 17% 2.1 vs. 2.5 p=0.19 Decrease in CVA 11% 1.3% vs. 1.5% p=0.5

15 Sprint Trial Required 2.8 vs 1.8 drugs Adverse Effects In pts w/o CKD >30% decrease in GFR to <60ml/min 3.8% vs. 1.1% p=0.001 Hypotension 2.4% vs. 1.4% p=0.001 Syncope 2.3% vs. 1.7% p=0.05 Hyponatremia 3.8% vs. 2.1% p=0.001

16 Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients Random and fixed effects analysis of 4 RCT totaling pts >65yo randomized to at least <140 sys vs. >140 Results 29% decrease in MACE 33% decrease in CV mortality 37% decrease in CHF Nonsignificant decreases in MI and CVA Increased risk of renal failure JACC VOL. 69, NO. 5, 2017 FEBRUARY 7, 2017:486 93

17 Hypertension in 2017 What Is the Right Target? JAMA. Published online January 30, doi: /jama

18 Age-adjusted mortality rates for coronary heart disease and stroke in the United States, % 58% Theodore A. Kotchen Hypertension. 2011;58: Copyright American Heart Association, Inc. All rights reserved.

19 Minnesota Deaths per 100,000 population 2001 CANCER BECOMES NO. 1 KILLER IN MINNESOTA Heart Disease Cancer

20 The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. United States Cardiovascular Deaths ( ) see more Deaths per 100,000 population % Year Number of deaths due to cardiovascular disease, including heart disease and stroke, per 100,000 population.

21 The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. Minnesota Cardiovascular Deaths ( ) see more Deaths per 100,000 population % Year Number of deaths due to cardiovascular disease, including heart disease and stroke, per 100,000 population. State Rank Value

22 The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. Minnesota Cardiovascular Deaths ( ) see more Deaths per 100,000 population % Year Number of deaths due to cardiovascular disease, including heart disease and stroke, per 100,000 population. State Rank Value

23 MN CO 196 Hawaii 203 Average 250 Mississippi 341

24 Life Expectancy

25 MINNESOTA LEADING THE WAY Because of a dramatic drop in heart disease deaths, cancer has become the leading killer in Minnesota for the first time. The shift puts Minnesota at the leading edge of what could be a historical national trend Minneapolis Star & Tribune Source: Minneapolis Star & Tribune Article 09/28/2003 (Maura Lerner - Cancer Becomes No. 1 Killer in State)

26 The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. Minnesota Cardiovascular Deaths ( ) see more Deaths per 100,000 population % Year Number of deaths due to cardiovascular disease, including heart disease and stroke, per 100,000 population. State Rank Value

27 MN MN 184.7

28 Obesity 66% of Americans are over weight 31.4% are obese 21% of teenagers are obese 15% of 5 year olds are obese

29 Diabetes

30 The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. Minnesota Obesity ( ) see more Percentage of adult population % Year Percentage of the population estimated to be obese, with a body mass index (BMI) of 30.0 or higher.

31 Percentage of adults who responded yes to the question "Have you ever been told by a doctor that you have diabetes?" (Excludes pre-diabetes and gestational diabetes). The measures tracked by America's Health Rankings are those actions that can affect the future health of the population. For a state to improve the health of its population, efforts must focus on these measures, these determinants of health. Minnesota Diabetes ( ) see more Percentage of adult population % Year 8.1 Percentage of adults who responded yes to the question "Have you ever been told by a doctor that you have diabetes?" Does not include pre-diabetes or diabetes during pregnancy.

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33 Take Home Gift 80% of all Mortality (including cardiac, stroke and cancer) can be predicted by 4 lifestyle choices Not smoking Healthy Diet Regular exercise Ideal body weight

34 Cardiovascular Excellence one patient at a time

35 Controversies in Hypertension and Are we Winning the Battle with Heart Disease

36 ACCORD Primary and Secondary TRIAL-BP Outcomes The Action to Control Cardiovascular Risk in Diabetics Blood Pressure The ACCORD Study Group. N Engl J Med 2010;362:

37 Sprint Trial Results CHF 1.3% vs 2.1% p=0.002 CV mortality.8% vs. 1.4% p= Mortality 3.3% vs 4.5% p= In pts w/o CKD >30% decrease in GFR to <60ml/min 3.8% vs. 1.1% p=0.001 Hypotension 2.4% vs. 1.4% p=0.001 Syncope 2.3% vs. 1.7% p=0.05 Hyponatremia 3.8% vs. 2.1% p=0.001

38 Sprint Trial Results Decrease in CHF 38% Decrease in CV mortality 43% Decrease in Overall Mortality 27% Decrease in Myocardial Infarctions 17% Decrease in CVA 11%

39 United States Deaths per 100,000 population DEATHS FROM HEART DISEASE DECLINE UNITED STATES Heart Disease Cancer

40 From: Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, JAMA. 2017;317(2): doi: /jama

41 PREVALENCE/MORTALITY Nearly 801,000 people in the U.S. died from heart disease, stroke and other cardiovascular diseases in That s about one of every three deaths in America. CVD is the No. 1 cause of death for women as well as men 10 times as many women will die of heart disease as breast cancer

42 Deaths per 100,000 population Decline in Deaths from Cardiovascular Disease in Relation to Scientific Advances Coronary arteriograp hy Developed (Sones) 1954 First Openheart procedure (Gibbon) 1962 First betablocker developed (Black) 1961 Risk factors defined 1961 Coronary care unit develope d (Julian) 1969 First description of CABG (Favaloro) 1976 First HMG CoA Reductase inhibitor (Endo) 1972 NHBP EP 1979 Coronary angioplasty developed (Grüntzig) 1980 First implantable cardioverterdefibrillator developed (Mirowski) 1983 CASS 1985 NCEP 1985 TIMI Superiority of primary PCI vs. fibrinolysis in acute MI noted GIS SI and ISIS SAVE 2007 Benefit of cardiac resynchronization therapy in heart failure demonstrated 2002 Efficacy of drug-eluting vs. baremetal stents determined 2002 ALLHAT 2009 Left-ventricular assist device as destination therapy in advanced heart failure shown to be effective 2009 Genome wide association in early-onset MI described 2009 Deep gene sequencing for responsiveness to cardiovascular drugs performed Nabel EG and Braunwald E. 2012;366:54-63

43 Corlanor (ivabradine) Indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with LVEF 35%, who are in sinus rhythm with resting heart rate 70 bpm and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. Side effects. bradycardia (10% vs. 2.2%) hypertension (8.9% vs. 7.8%) atrial fibrillation (8.3% vs. 6.6%) luminous phenomena (phosphenes) or visual brightness (2.8% vs. 0.5%).

44 Block Buster Drugs The PCSK9 INHIBITORS are a new class of drugs that have been shown to dramatically lower LDL cholesterol levels. PCSK9 inhibitors are monoclonal antibodies (MABs), a type of biologic drug. They inactivate a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9). PCSK9 itself inactivates the needed receptors on the liver cell surface that transport LDL into the liver for metabolism (break down). Without these receptors, more LDL ("bad" cholesterol) remains in the blood. So, by inactivating PCSK9 via inhibition, more receptors are available to capture LDL for metabolism and removal from the blood. They can lower LDL by 60% on top of statins. Alirocumab (Praluent) by Sanofi and Regeneron Evolocumab (Repatha) by Amgen

45 Block Buster Drugs The PCSK9 INHIBITORS are a new class of drugs that have been shown to dramatically lower LDL cholesterol levels. PCSK9 inhibitors are monoclonal antibodies (MABs), a type of biologic drug. They inactivate a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9). PCSK9 itself inactivates the needed receptors on the liver cell surface that transport LDL into the liver for metabolism (break down). Without these receptors, more LDL ("bad" cholesterol) remains in the blood. So, by inactivating PCSK9 via inhibition, more receptors are available to capture LDL for metabolism and removal from the blood. They can lower LDL by 60% on top of statins. Alirocumab (Praluent) by Sanofi and Regeneron Evolocumab (Repatha) by Amgen

46 PARADIGM-HF Side effects Hypotension 18% vs. 12% Hyperkalemia 12% vs.14% Rise in Cr 5% vs. 5% Angioedema.5% vs.2% Cough 9% vs. 13%? Dementia Contraindicated in pregnancy and ACE I Lithium toxicity.

47 PARADIGM-HF CV Death and CHF hospitalization (21.8% vs 26.5%) Cardiovascular Death (13.3% vs 16.5%) First hospitalization for CHF (12.8% vs 15.6%) All cause mortality (17.0% vs 19.8%)

48 PARADIGM-HF 8442 pts with LVEF<40% NYHA CHF Class 2 (72%) and 3 (23%) Randomized to Entresto vs Enalapril Stopped early, 27 months

49 Block Buster Drugs Entresto contains a combination of sacubitril and valsartan. (ARNi Angiotensin Receptor- Nephrilysin inhibitor) Sacubitril is a nephrilysin inhibitor. Nephrilysin is an endopeptidase that degrades vasoactive peptidases such as BNP, bradykinin and adrenomedulin. It works by vasodilating blood vessels and increases sodium excretion. Valsartan is an angiotensin II receptor blocker (ARB). Valsartan vasodilates blood vessels which lowers blood pressure, improving blood flow and decrease the cardiac workload. Novartis Entresto reduced the risk of death from cardiovascular causes and heart failure hospitalization by 20% and 21%, respectively, and reduced the risk of all-cause mortality by 16%.

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51 Increases risk of heart disease 2-3x Down from 42% to 18% 8 million lives saved but still 17.7 million deaths 443,000 deaths annually 4000 teenagers start every day

52 Smoking Bans A meta analysis of 45 studies 15% decrease in MI hospitalizations. 16% drop in strokes 24% drop in respiratory hospitalizations

53 ASPIRIN 1988 International Study of Infarct Survival 2 (ISIS-2) patients with suspected MI s ASA and/or Streptokinase Results ASA decreased mortality by 21% Streptokinase decreased mortality by 23% ASA + Strepto decreased mortality by 39% Lancet 1988;8:350-60

54 cvriskcalculator.com

55 cvriskcalculator.com

56 BETA BLOCKERS ISIS-1 First International Study of Infarct Survival was a study of 16,027 patients demonstrating that IV beta blockers given acutely in an AMI decreased 7 day mortality from 4.6% to 3.9%. A meta analysis of 28 trials demonstrated 16% decrease in mortality 18% decrease in reinfarction 15% decrease in Ventricular fibrillation

57 ACE INHIBITORS 1991 Survival and Ventricular Enlargement (SAVE) 2231 patients post MI with EF <40% Randomized to captopril vs. placebo Results 21% decrease in cardiac mortality 36% decrease in death and CHF 25% decrease in reinfarction Recommendation: All MI s with EF<40% without hypotension. Consider use in all MI s

58 This is an incredibly exciting time. I believe History will look back on this time as the Golden Age of Cardiology, the time when the battle with cardiovascular disease was fought and eventually won.

59 MINNESOTA LEADING THE WAY Since the 1990 s the death rate from heart disease has dropped faster in Minnesota than any other state- a whopping 45%... One of the greatest success stories of modern medicine StarTribune Jan