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2017Hypertension Update J. Paul Martin, MD

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1 2017Hypertension Update J. Paul Martin, MD

2 Linville viaduct

3 Cold Mountain – Civil war novel by Charles Frazier author
2003 Movie Nicole Kidman, Rene Zellweger, Jude Law -

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7 NC State Ctr for Hlth Stats
WNC Higher Than the National Ave. Hypertension Diabetes Elevated Cholesterol Obesity NC State Center for Health Statistics 74% overweight or obese in WNC; “Diabesity”

8 Hypertension WNC Higher Than the National Ave. 1 in 3 Adults in US have HTN Our local HRA’s found >50% HTN in several employee groups 55 YO with normal BP has 90% chance of developing HTN during lifetime <50% of those treated reach goal NC State Center for Health Statistics 74% overweight or obese in WNC; “Diabesity”

9 Joint National Committee
On Prevention, Detection, Evaluation And Treatment of High Blood Pressure (JNCOPDEATOHBP8) US Dept. of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute JNC 1 – normal diastolic <90 JNC 3 – 1984 normal systolic < 140 isolated systolic htn >160 JNC 7 – 2003 normal < 120/80 JNC 8 – December 2013 normal <120/80 The Department of Health and Human Services (HHS) is the United States government’s principal agency for protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves. NIH is the nation’s medical research agency—supporting scientific studies that turn discovery into health. Other NHLBI guidelines: Cholesterol Guideline Update – ATP IV • Hypertension Guideline Update – JNC 8 • Obesity Guideline Update – Obesity 2 • Integrated Cardiovascular Risk Reduction Guideline

10 BP Classification (JNC-8)
Normal < 120/80 Pre-hypertensive – /80-89 Hypertension >140/90 Stage 1: /90-99 Stage 2: > 160/100 The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

11 Other Advisory Groups American Diabetes Association
American Society of Hypertension /International Society of Hypertension European Society of Hypertension/ European Society of Cardiology The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

12 Proper BP Measurement Each 6 inch difference in height between the center of the cuff and heart will change the BP by 10 mm Hg.

13 Proper BP Measurement Locate brachial artery on inner upper arm
Place the middle of the cuff over the brachial artery. The lower edge of the cuff should be 1” above the antecubital space. Tell the patient not to talk Determine the maximum inflation point by palpating the radial artery and rapidly inflating cuff (palpated systolic). To that add 30 mm Hg The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

14 Proper BP Measurement Deflate cuff rapidly and wait 15 – 30 seconds before re-inflating. Apply the stethoscope bell lightly over the palpated brachial artery Inflate cuff rapidly to palpable systolic pressure + 30 mm Hg Release the air so pressure drops 3 mm Hg/sec The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

15 Proper BP Measurement Listen for at least two consecutive beats (Korotkoff sounds Phase 1) i.e. the systolic BP Listen for a muffling of the sounds in children or the absence of the sounds in adults (Korotkoff sounds Phase 4 or 5). This is the diastolic BP Continue listening for an additional deflation of 10 – 20 mm Hg to confirm findings. Don’t repeat for 1-2 minutes to allow trapped blood to be released from veins. The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

16 Proper BP Measurement Total Time: 5 minutes sitting 30 seconds to apply & palpate systolic BP 30 seconds wait 45 seconds to re -inflate & slowly deflate Total Time approx. 7 minutes The Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8 is imminent (2012) US HHS. JNC For those over 50 yrs of age Systolic BP >140 has more adverse effect on CVD than diastolic. 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits.

17 Treatment of high blood pressure
WHY? Decrease risk of stroke 35-40% Decrease risk of heart attack 20 – 25% Decrease risk of CHF > 50% Blindness, kidney failure, Unlike modifying homocysteine, BP control does improve CVD outcome.

18 Treatment of high blood pressure
In stage 1 HTN and additional CVD risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

19 Treatment of high blood pressure
> 60 yrs of age systolic BP is major predictor of coronary artery disease 50-59 systolic and diastolic BP are equal predictors of coronary artery disease < 50 Y/O diastolic BP is major predictor of coronary artery disease

20 Treatment of high blood pressure
What is the target? Blindness, kidney failure,

21 BP Treatment Recommendations
Joint National Committee Normal < 120/80 Pre-hypertensive – /80-89 NOT a disease category It IS a risk category Prehypertension is not a disease category. Rather, it is a designation chosen to identify individuals at high risk of developing hypertension, so that both patients and clinicians are alerted to this risk and encouraged to intervene and prevent or delay the disease from developing.

22 Treatment of high blood pressure
What is the target? Blindness, kidney failure,

23 Treatment of high blood pressure
What is the target? < 140/90 Blindness, kidney failure,

24 Treatment of high blood pressure
What is the target? < 140/90 …..with some caveats JNC-8 Blindness, kidney failure,

25 PVD – Peripheral Vascular Disease
Definitions CVD – Cardiovascular Disease PVD – Peripheral Vascular Disease CBVD – Cerebrovascular Disease CAD – Coronary Artery Disease RVD – Renal Vascular Disease Blindness, kidney failure,

26 Definitions Uncontrolled BP (>140/90 mmHg) despite: the use of 3 antihypertensives including a diuretic = Resistant Hypertension the use of 5 antihypertensives including long-acting thiazide and mineralocorticoid receptor antagonist = Refractory Hypertension Long acting diuretics: chlorthalidone, indapamide Mineralocorticoid recepetor antagonists – spironolactone (Aldactone), eplerenone ( Inspra)

27 Joint National Committee
JNC 1 – Thiazides for DBP >105 JNC 3 – 1984 ß-Blockers added as initial therapy option JNC 4 – 1988 ACEI and CBB added as initial therapy options (despite no RCT’s) JNC 5 – 1993 Evidence-based: Thiazides and ß-Blockers preferred initial agents JNC 6 – 1997 Any of the seven classes could be appropriate initial option JNC1- Therapy could be considered for those with DBP >90<105 JNC 3 – SBP > 160 considered isolated systolic htn. No tx for isolated SBP

28 JNC 7 - 2003 Thiazides as initial therapy for “most”
ACEI, ARBs, CCBs, ß-Bs appropriate first line in those with compelling indication Stage 2 hypertensives (> 160/100) should be started on two medications (one a thiazide) BP target for high-risk CVD <130/80 Antihypertensive Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) demonstrated that chlorthalidone is superior at preventing CVD events compared to each of the treatment drugs studied: calcium channel blocker (amlodipine), ACE inhibitor (lisinopril), and alpha-adrenergic blocker (doxazosin). Compelling indications included Heart failure, post MI, DM, s/p CVA, BP<130/80 to be consistent with ADA and NKF guidelines

29 JNC 7 - 2003 Thiazides as initial therapy for “most”
ACEI, ARBs, CCBs, ß-Bs appropriate first line in those with compelling indication Stage 2 hypertensives (> 160/100) should be started on two medications (one a thiazide) BP target for high-risk CVD <130/80 The British Hypertension Society & National Institute for Health and Clinical Excellence in the UK removed beta-blockers as first-line therapy for uncomplicated htn after the Allhat & LIFE trials (Losartan Intervention for End Point Reduction Trial)

30 JNC The JNC-8 guidelines provide practice guidance for patients aged ≥18 years across a number of pre-specified subgroups, such as diabetes, chronic kidney disease, CVD, older adults, sex, racial and ethnic groups, and smokers.

31 What constitutes good care?
How important is diet, exercise, weight control? What medications are available? Which ones actually work? How low should you go?

32 Diet, Exercise, & Weight Management

33

34 Diet, Exercise, & Weight Management

35 Treatment of high blood pressure
Diet mmHg Exercise mmHg Weight control mmHg/10Kg Dietary NaCl mmHg Magnesium mmHg Approx SBP reduction Diet –The heart of the DASH diet is an eating plan rich in fruits and vegetables, low-fat and nonfat dairy, along with nuts, beans, and seeds, substitution of fish and poultry for red meat, limited intake of fats and sweets. Dietary Approaches to Stop Hypertension (DASH) Achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated. Only about 1/3 of the population is NA sensitive. Low sodium diet = 3 grams NaCl / day. Mg supplementation will reduce diastolic by 3.4mm HG. Magnesium is depleted by diuretics, and low magnesium is assoc with development of insulin resistance.

36 Diet, Exercise, Weight Management
74% overweight or obese in WNC; “Diabesity”

37 Primary Prevention of HTN
Calcium supplementation, fish oil, reduction of caffeine: Prudent for general health Minimal effect on lowering BP or preventing HTN Diet –The heart of the DASH diet is an eating plan rich in fruits and vegetables, low-fat and nonfat dairy, along with nuts, beans, and seeds. Achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

38 Primary Prevention of HTN
Drugs which may induce hypertension: Adrenal Steroids Oral Contraceptives NSAIDS Stimulants Sympathomimetics Stimulants –Amphetamines, methylphenidate, modafinil/armodafinil(Provigil/Nuvigil) Sympathomimetics – phenylephrine, ephedra, Ma huang, bitter orange

39 Primary Prevention of HTN
While caffeine can acutely increase BP, studies have not shown a linear relationship between caffeine intake and incident morbidity To judge effect of caffeine on your BP, measure BP minutes after intake. Diet –The heart of the DASH diet is an eating plan rich in fruits and vegetables, low-fat and nonfat dairy, along with nuts, beans, and seeds. Achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

40 What constitutes good care?
How important is diet, exercise, weight control? What medications are available? Which ones actually work? How low should you go?

41 Medications 74% overweight or obese in WNC; “Diabesity”

42 Medications

43 Medications Thiazides Beta Blockers ACEI / ARBs
Calcium Channel Blockers Mineralocorticoid Receptor Antagonists Alpha 2 Adrenergic Agonists Alpha 1 Adrenergic Receptor Blockers Direct Vasodilators HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

44 Medications - Thiazides
JNC-7 - Thiazide Diuretics should be initial hydrochlorothiazide (hctz), chlorthalidone, indapamide Most patients will require more than one medication to reach their BP goal JNC7 indapamide = Lozol (discontinued) T1/2 = 26 hours

45 Medications - Thiazides
Hydrochlorothiazide doses > 25mg/d are seldom justifiable based on published evidence of outcomes & adverse effects Long acting thiazides such as chlorthalidone and indapamide are indicated in resistant or refractory hypertension JNC7 indapamide = Lozol ( branded discontinued) T1/2 = 26 hours

46 Medications - Thiazides
Thiazide diuretics, which are the most commonly used diuretic, inhibit the sodium-chloride transporter in the distal tubule. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis. Nevertheless, they are sufficiently powerful to satisfy most therapeutic needs requiring a diuretic. Their mechanism depends on renal prostaglandin production.

47 Medications - Thiazides
Thiazides may induce glucose intolerance Keep Potassium > 4.0 mEq/L (consider KCl, ACEI, ARB, triamterene, amiloride, spironolactone) Prior Stroke – Thiazide & ACEI In HYVET (age >80) indapamide + ACEI 21% decrease in all cause mortality 30% reduction in CVA 64% reduction in CHF HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

48 Medications - Thiazides
Reduce excretion of: Calcium (fewer Ca++ kidney stones) Uric Acid ( increasing risk of gout) Lithium (increasing risk of toxicity) Increase excretion of: Potassium Magnesium HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

49 Medications - Thiazides
NaCl restriction enhances response to thiazides High Dietary salt intake offsets response HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

50 Medications – Loop Diuretics
Thiazide diuretics typically considered ineffective when GFR < ml/min (except metolazone-Zaroxyln) Substitute furosemide or torsemide (loop diuretics) Torsemide – Demadex; Ethacrynic Acid, bumetanide (Bumex), mecurial diuretics

51 Medications – Loop Diuretics
Thiazide diuretics, which are the most commonly used diuretic, inhibit the sodium-chloride transporter in the distal tubule. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis. Nevertheless, they are sufficiently powerful to satisfy most therapeutic needs requiring a diuretic. Their mechanism depends on renal prostaglandin production.

52 Medications – Beta Blockers
Beta Blockers have fallen from grace as single agents in HTN except in patients with CAD (?) Atenolol should be given BID Avoid Beta Blockers in Prinzmetal Angina JAMA Oct 3, ,000 patient observation – no lower risk of composite CV events with Beta Blockers even in patients s/p MI (distant) – REACH study Atenolol – Tenormin Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia 2008 COMMIT Study 46,000 patients in China – no improved outcome with metoprolol in Acute MI

53 Medications – Beta Blockers
Older beta-blockers (propranolol, atenolol, metoprolol) worsen insulin resistance The vasodilating beta-blockers (carvedilol, labetolol, nebivolol) don’t have this effect Atenolol – Tenormin May also cause increased triglycerides Nebivolol – Bystolic Labetolol - trandate Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia

54 Medications – Beta Blockers
Cochrane Database Syst Rev 2007 RCTs assessing the effectiveness of beta blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for HTN, on morbidity and mortality endpoints 13 RCTs; 91,561 subjects Available evidence does not support the use of beta blockers as first-line agents in HTN treatment Atenolol – Tenormin May also cause increased triglycerides. Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia

55 Medications – Beta Blockers
Bisoprolol (Zebeta), carvedilol (Coreg) and sustained-release metoprolol (ToprolXL) are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure. Atenolol – Tenormin Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia

56 Rebound Hypertension Medications – Beta Blockers
Short –acting β-blockers such as: Propranolol Atenolol Metroprolol Rapid disappearance of β-blockade -Loss of protection against ischemia -Loss of antihypertensive effect -Subsequent enhanced β-receptor mediated responses Atenolol – Tenormin Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia

57 Rebound Hypertension Medications – Beta Blockers
Partial compliance with β-blocker treatment is Associated with increased risk of sudden death Short –acting β-blockers such as: Propranolol Atenolol Metroprolol Rapid disappearance of β-blockade -Loss of protection against ischemia -Loss of antihypertensive effect -Subsequent enhanced β-receptor mediated responses Atenolol – Tenormin Design, Setting, and Patients  Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14 043), known CAD without MI (n = 12 012), or those with CAD risk factors only (n = 18 653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. Main Outcome Measures  The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. Side effects: abradycardia, AV block, bronchospasm, hyperkalemia

58 Medications ACEI/ARBs
ACE Inhibitors (benazepril, enalapril, lisinopril) ARB (losartan, irbesartan, candesartan, valsartan) Cough, angioedema, hyperkalemia, ARF ONTARGET – no benefit combining - led to increased renal impairment ACEI still have more evidence than ARBs for improving outcomes. Losartan (Cozaar) is probably the weakest ARB. All ACEI and ARBs contraindicated in pregnancy 2012:irbesartan (Avapro) in March...valsartan (Diovan) in Sept...and candesartan (Atacand) in Dec only candesartan and valsartan are approved for heart failure.    But their benefits are likely a class effect. In general, feel comfortable using any ARB...as long as it's dosed appropriately.    Aim for the highest tolerated approved dose...especially for heart failure. For losartan, go up to 150 mg/day for heart failure. The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmisartan, and their combined use with respect to CV events. Telmisartan (Micardis) won’t be available as generic until 2014

59 Medications ACEI/ARBs
ACE Inhibitors, ARBs and Aldosterone Inhibitors all lessen insulin resistance ACEI still have more evidence than ARBs for improving outcomes. Losartan (Cozaar) is probably the weakest ARB. All ACEI and ARBs contraindicated in pregnancy 2012:irbesartan (Avapro) in March...valsartan (Diovan) in Sept...and candesartan (Atacand) in Dec only candesartan and valsartan are approved for heart failure.    But their benefits are likely a class effect. In general, feel comfortable using any ARB...as long as it's dosed appropriately.    Aim for the highest tolerated approved dose...especially for heart failure. For losartan, go up to 150 mg/day for heart failure. The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmisartan, and their combined use with respect to CV events. Telmisartan (Micardis) won’t be available as generic until 2014

60 African Americans & ACEI/ARBs
Htn is commonly of low renin type Sensitivity of blood pressure to salt intake is often increased The ability to excrete ingested salt is impaired (60–70%) This leads to an overall expansion of intravascular volume. Obesity is especially prevalent in black women and is associated with an increase in total body sodium content. Intake of dietary potassium, in the form of fruit and vegetables, is generally lower in blacks than in whites. Black patients may also have relatively higher concentrations of intracellular calcium In view of the increased sensitivity of black patients to salt, restricting dietary salt intake to less than 6 g daily is particularly effective at reducing blood pressure. Ensuring a low dietary salt intake can improve the blood pressure response to ACE inhibitors in black patients.26 Heart Aug; 91(8): 1105–1109 “Management of Hypertension in Ethnic Minorities”

61 Medications ACEI/ARBs
ACEI still have more evidence than ARBs for improving outcomes. Losartan (Cozaar) is probably the weakest ARB. All ACEI and ARBs contraindicated in pregnancy 2012:irbesartan (Avapro) in March...valsartan (Diovan) in Sept...and candesartan (Atacand) in Dec only candesartan and valsartan are approved for heart failure.    But their benefits are likely a class effect. In general, feel comfortable using any ARB...as long as it's dosed appropriately.    Aim for the highest tolerated approved dose...especially for heart failure. For losartan, go up to 150 mg/day for heart failure. The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmisartan, and their combined use with respect to CV events. Telmisartan (Micardis) won’t be available as generic until 2014

62 Medications ACEI/ARBs
ACEI still have more evidence than ARBs for improving outcomes. Losartan (Cozaar) is probably the weakest ARB. All ACEI and ARBs contraindicated in pregnancy 2012:irbesartan (Avapro) in March...valsartan (Diovan) in Sept...and candesartan (Atacand) in Dec only candesartan and valsartan are approved for heart failure.    But their benefits are likely a class effect. In general, feel comfortable using any ARB...as long as it's dosed appropriately.    Aim for the highest tolerated approved dose...especially for heart failure. For losartan, go up to 150 mg/day for heart failure. The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmisartan, and their combined use with respect to CV events. Telmisartan (Micardis) won’t be available as generic until 2014

63 Medications ACEI/ARBs
Should be use in the population > 18 yrs with CKD or DM to improve kidney outcomes This is regardless of race Do NOT use an ACEI and ARB together ACEI still have more evidence than ARBs for improving outcomes. Losartan (Cozaar) is probably the weakest ARB. All ACEI and ARBs contraindicated in pregnancy 2012:irbesartan (Avapro) in March...valsartan (Diovan) in Sept...and candesartan (Atacand) in Dec only candesartan and valsartan are approved for heart failure.    But their benefits are likely a class effect. In general, feel comfortable using any ARB...as long as it's dosed appropriately.    Aim for the highest tolerated approved dose...especially for heart failure. For losartan, go up to 150 mg/day for heart failure. The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmisartan, and their combined use with respect to CV events. Telmisartan (Micardis) won’t be available as generic until 2014

64 Medications ACEI/ARBs
42 YO Asian female with HTN and type 2 DM has baseline serum Cr of 1.7 mg/dL. Her BP is 147/92. She is started on lisinopril. Two weeks later her BP is 128/78. Her serum Cr = 2.1. A repeat serum Cr 1 week later is unchanged. Which is the most appropriate course of action?

65 Medications ACEI/ARBs
A. Continue the lisinopril at the same dosage B. Reduce the lisinopril dosage C. Discontinue the lisinopril D. Switch to an ARB E. Evaluate the patient for bilateral renal stenosis A 20-30% increase in Cr, which then stabilizes represents a hemodynamic change and NOT a structural change. The slight rise in CR serve as an indirect indicator that IG pressure has been reduced. Renal dysfunction associated with antihypertensive treatment is independent of the agent used. ACEI/ARB also dilate efferent arteriole exaggerating the decline in IG pressure. If CR increases by more than 30% agent should be discontinued and other causes of renal dysfunction evaluated.

66 Medications - CCBs Dihydropyridines (amlodipine, nifedipine)
Non-dihydropyridines (verapamil, diltiazem)

67 Medications - CCBs Nondihydropyridine CCB slow SA Node and decrease myocardial contractility and have minimal vasodilation effects. Dihydropyridine CCB have marked vasodilation effects but minimal effects on myocardial contractility and SA node depression.

68 JNC 7 - 2003 Thiazides as initial therapy for “most”
ACEI, ARBs, CCBs, ß-Bs appropriate first line in those with compelling indication Stage 2 hypertensives (>160/100) should be started on two medications (one a thiazide) BP target for high-risk CVD <130/80 Antihypertensive Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) favored thiazides as initial therapy. Compelling indications included Heart failure, post MI, DM, s/p CVA, BP<130/80 to be consistent with ADA and NKF guidelines

69 Medications for Compelling Indications
Htn & Stable Angina – beta blocker (?CCB) Htn & CHF – beta blocker & ACEI Chronic Kidney Disease – ACEI or ARB Diabetes – ACEI or ARB Prior Stroke – Thiazide & ACEI ACEI still have more evidence than ARBs for improving outcomes. PROGRESS: 2001 Thiazide and ACEI COMMIT & REACH both dispute value of BB in angina Us high dose ACEI in HF – Lisinopril >30mg

70 JNC Thiazides ACEI, ARBs, CCBs, appropriate first line based on physician/patient preference. Thiazides and calcium channel blockers are preferred for black patients because of improved cardiovascular and cerebrovascular outcomes, and more effective blood pressure reduction in this population. African Americans and Asians have a 3-4 fold higher risk of angioedema with ACE inhibitors than whites. AHA recommends that ACE inhibitors NOT be used in any patient with a history of angioedema.

71 JNC If after 30 days BP has not reached goal of <140/90 either the dose should be increased or a second drug added from initial list Antihypertensive Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) favored thiazides as initial therapy. Compelling indications included Heart failure, post MI, DM, s/p CVA, BP<130/80 to be consistent with ADA and NKF guidelines

72 JNC 54 YO African American female presents for routine evaluation with BP 164/106. Which antihypertensive meds would you initially consider? Chlorthalidone & Amlodipine Lisinopril & Atenolol Losartan (Cozaar) & Atenolol Prazosin & Atenolol Clonidine or Minoxidil African Americans and Asians have a 3-4 fold higher risk of angioedema with ACE inhibitors than whites. AHA recommends that ACE inhibitors NOT be used in any patient with a history of angioedema. Correct Answer- Chlorthalidone and Norvasc.

73 Medications Thiazides Beta Blockers ACEI / ARBs
Calcium Channel Blockers Mineralocorticoid Receptor Antagonists Alpha 2 Adrenergic Agonists Alpha 1 Adrenergic Receptor Blockers Direct Vasodilators HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

74 Mineralocorticoid Receptor Antagonists
In resistant or refractory HTN consider spironolactone In HTN associated with Obstructive Sleep Apnea consider spironolactone (Aldactone) Eplerenone (Inspra) is 6X as expensive – reserve for those requiring >50mg spironolactone with side effects Antagonizes aldosterone-specific mineralocorticoid receptors primarily in the distal convoluted tubule, decreasing Na and water reabsorption and increasing K retention Contraindicated with CrCl<10 (Cr >2.6 Side effects – gynecomastia, sexual dysfunction, hyperkalemia, hyperuricemia, headache, n/v.

75 Medications - Spironolactone

76 Alpha-2 Adrenergic Agonists
Centrally-acting Clonidine (Catapres) Guanfacine (Tenex) Methyldopa (Aldomet) Dexmedetomidine (Precedex), Tizanidine (Zanaflex) Similar in action to dexmedetomidine (Precedex) Tizanidine (Zanaflex) is a central alpha-2 adrenergic agonist!

77 Centrally-acting Alpha-2 Adrenergic Agonists
Similar in action to dexmedetomidine (Precedex). Clonidine is an agonist, not a receptor blocker – causes inhibition but not blockade of sympathetic vasomotor centers.

78 Slow heart rate / lower BP
Centrally-acting Alpha-2 Adrenergic Agonists Slow heart rate / lower BP Potential for rebound HTN (esp. >1.2mg clonidine long term >2 months) Should be avoided in CHF – negative chronotropic and inotropic effects. Abrupt withdrawal can cause rapid increase in SBP and DBP . Concommitant use of Beta Blockers results in unopposed peripheral alpha activity increasing severity of rebound.

79 Off Label Chronic Pain (neurogenic/hypersensitivity) ADD/ADHD
Centrally-acting Alpha-2 Adrenergic Agonists Off Label Chronic Pain (neurogenic/hypersensitivity) ADD/ADHD Narcotic Withdrawal Behavioral Issues Abrupt withdrawal can cause rapid increase in SBP and DBP . Concommitant use of Beta Blockers results in unopposed peripheral alpha activity increasing severity of rebound.

80 Alpha-1 Adrenergic Receptor Blockers
Peripheral Doxazosin (Cardura) Prazosin (Minipress) Terazosin (Hytrin) ALLHAT study in 2000: doxazosin arm was stopped early (in March 2000) due to a 25 percent higher rate of combined CVD and a two-fold higher rate of heart failure compared to the diuretic arm. The results were published in the April 19, 2000, JAMA. Alpha-blockers, therefore, should not be considered for initial therapy. Flomax - tamsulosin

81 Peripherally-acting Alpha-1 Adrenergic Blockers

82 Potpourri of Medication Updates
Direct Vasodilators Hydralazine (Apresoline) Minoxidil Minoxidil topical = Rogaine Although minoxidil is extremely effective, its usefulness is limited by its tendency to increase the pulse rate and to trigger salt and water retention. The latter may be incapacitating in some patients. Therefore, minoxidil is typically administered with both a diuretic and an agent that can control the pulse rate, such as a beta blocker.

83 Medications Thiazides Beta Blockers ACEI / ARBs
Calcium Channel Blockers Mineralocorticoid Receptor Antagonists Alpha 2 Adrenergic Agonists Alpha 1 Adrenergic Receptor Blockers Direct Vasodilators HYVET – hypertension in the very elderly trial PROGRESS study in 2001 showed benefit of thiazides ACEI Side effects: Hyperuricemia, hyperlipidemia, hypercalcemia, siadh Amiloride – “Midamor” discontinued.

84 Treatment of high blood pressure
What is the target? < 140/90 …..with some caveats Blindness, kidney failure, The most significant change in the JNC 8 guideline is relaxation of the systolic and diastolic blood pressure goals for adults 60 years and older. This finding was based primarily on six randomized controlled trials (RCTs) comparing intensive vs. conservative blood pressure goals among older patients

85 JNC-8 Target for Age >60
<150/90 <140/90 if tolerated with no adverse effects and for those with high CV risk In the general population of adults 60 years and older, pharmacologic treatment should be initiated when the systolic pressure is 150 mm Hg or higher, or when the diastolic pressure is 90 mm Hg or higher. Patients should be treated to a target systolic pressure of less than 150 mm Hg and a target diastolic pressure of less than 90 mm Hg. Treatment does not need to be adjusted if it results in a systolic pressure lower than 140 mm Hg, as long as it is not associated with adverse effects on health or quality of life. High cv risk generally includes patients with diabetes, vascular disease, metabolic syndrome or ckd Endorsed by ACP & AAFP 2017

86 JNC-8 Target for DM or CKD
<140/90 for all > 18 yrs of age In the general population of adults 60 years and older, pharmacologic treatment should be initiated when the systolic pressure is 150 mm Hg or higher, or when the diastolic pressure is 90 mm Hg or higher. Patients should be treated to a target systolic pressure of less than 150 mm Hg and a target diastolic pressure of less than 90 mm Hg. Treatment does not need to be adjusted if it results in a systolic pressure lower than 140 mm Hg, as long as it is not associated with adverse effects on health or quality of life.

87 Treatment of high blood pressure
AHA 2007 guidelines: < 120/80 with LV Dysfunction CAD risk equivalents – PVD, AAA, Carotid Artery Disease Blindness, kidney failure,

88 Treatment of high blood pressure
ADA 2013 Clinical Practice Recs: <140 SBP <130 SBP may be appropriate for younger patients Based on ACCORD study Blindness, kidney failure,

89 Can too low be bad? In the elderly DBP<65 is potentially dangerous
For very elderly patients - Begin with a single drug - Standing BP should be checked after 5 minutes - SBP<130 & DBP<65 should be avoided Blindness, kidney failure,

90 Can too low be bad? YES In the elderly DBP<65 is potentially dangerous For elderly patients - Begin with a single drug - Standing BP should be checked after 5 minutes - SBP<130 & DBP<65 should be avoided Blindness, kidney failure,

91 Treatment of high blood pressure
What is the target? < 140/90 …..with some caveats Blindness, kidney failure,

92 What constitutes good care?
How important is diet, exercise, weight control? What medications are available? Which ones actually work? How low should you go?

93 JNC - 9 What Should We Expect?

94 JNC - 9 What Should We Expect? It‘s tough to make predictions, especially about the future. Yogi Berra

95 JNC - 9 What Should We Expect?
SPRINT trial – target systolic 120 mmHg in nondiabetics >50 years % lower HF/CVD & all cause mortality, Stopped due to benefit after 3.26 yrs. N Engl J Med 2015:373: Aggressive treatment of individuals with proteinuria to prevent ESRD Guidelines will only be based on RCTs. ACCORD demonstrated no value in intensive tx of diabetics or CRF. The doxazosin arm (ALLHAT) was stopped early (in March 2000) due to a 25 percent higher rate of combined CVD and a two-fold higher rate of heart failure compared to the diuretic arm. The results were published in the April 19, 2000, JAMA. Alpha-blockers, however, should not be considered for initial therapy.

96 JNC - 9 What Should We Expect? 3. Aggressive treatment of individuals post-stroke & diabetes Guidelines will only be based on RCTs. ACCORD demonstrated no value in intensive tx of diabetics or CRF. The doxazosin arm (ALLHAT) was stopped early (in March 2000) due to a 25 percent higher rate of combined CVD and a two-fold higher rate of heart failure compared to the diuretic arm. The results were published in the April 19, 2000, JAMA. Alpha-blockers, however, should not be considered for initial therapy.

97 What’s New Renal Artery Denervation
Renal denervation (RDN) is a minimally invasive, endovascular catheter based procedure using radiofrequency ablation aimed at treating resistant hypertension. By applying radiofrequency pulses to the renal arteries, the nerves in the vascular wall (adventitia layer) can be denervated. This causes reduction of renal sympathetic afferent and efferent activity and blood pressure can be decreased.[1] Early data from international clinical trials is promising demonstrating average blood pressure reduction of approximately 30mm Hg at three year follow up in patients with treatment-resistant hypertension.[2][3] Since 2007 over 4000 patients have undergone catheter based renal denervation with the Medtronic Symplicity™ Renal Denervation System.[4] Symplicity HTN-4 is the next step in Medtronic's global renal denervation clinical program designed to carefully and progressively build the clinical evidence platform for the treatment of hypertension. This is being accomplished through a series of trials, which include more than 250 patients already enrolled in the Symplicity HTN-1 and Symplicity HTN-2 studies, 530 patients being enrolled in the Symplicity HTN-3 study, and 5,000 patients being enrolled in the Global SYMPLICITY Registry. The robust SYMPLICITY global dataset with planned follow-up to 5 years in most studies will be utilized to evaluate not only blood pressure reduction, but also long-term cardiovascular outcomes from hypertension such as stroke, myocardial infarction, heart failure and cardiovascular death. Medtronic's rigorous clinical evaluation program of the Symplicity renal denervation system includes more than 8,000 patients worldwide, including studies in the U.S., China, and Japan, with over 1,200 of these patients participating in randomized clinical trials

98 Renal Denervation 4 Trial (Phase III) Inclusion Criteria:
Individual is on maximally tolerated stable medication regimen including 3 or more anti-hypertensive medications of different classes, one of which must be a thiazide or thiazide-like diuretic Individual has office SBP greater than or equal to 140mmHg and less than 160mmHg Individual has ABPM average SBP greater than or equal to 135 mmHg Exclusion Criteria: Individual lacks appropriate renal artery anatomy Individual has eGFR of less than 30 Individual has Type I diabetes mellitus Individual has had one or more episodes of orthostatic hypotension Individual requires chronic oxygen other than nocturnal respiratory support for sleep apnea Individual has primary pulmonary hypertension Individual has other concomitant conditions that may adversely affect the patient or the study outcomes Individual is pregnant, nursing or planning to be pregnant Individual has had a previous organ transplant

99 So What Do We Do Today? Try to get most patients <140/90
Pts > 60 yrs w chronic volume depletion or susceptible to orthostasis <150/90 may be acceptable Patients at high risk of CHF or CVA there appears to be benefit to decrease systolic BP to 120 with NNT of only 61 over 3 yr period. Blindness, kidney failure,

100 Questions?

101 Hypertension Case Studies #1
39 YO White male with unremarkable PMH. Exam reveals an obese male with a round face and plethoric complexion. BP 156/98 P=82 R=16/min Prominent dorsal cervical and supraclavicular fat pads. Violaceous striae on trunk Lab notable only for FBG = 114mg/dL Plethoric - Characterized by an overabundance of blood.

102 Hypertension Case Studies #1
Plethoric - Characterized by an overabundance of blood.

103 What is most likely diagnosis?
Hypertension Case Studies #1 What is most likely diagnosis? A. Primary hyperaldosteronism B. Pheochromocytoma C. Hemochromatosis D. Cushing’s syndrome E. Addison’s disease Correct Answer – D. Cushing disease – glucocorticoid excess due to excessive ACTH secretion from pituitary tumor Cushing syndrome – excessive corticosteroid exposure from exogenous sources: medications – most common cause OR endogenous sources pituitary or adrenal tumor or small cell CA of lung, etc.

104 Resistant Hypertension
Hard to Treat Hypertension Resistant Hypertension Three or more medications including a diuretic Consider switching to long-acting thiazide Add Spironolactone Long acting thiazides – chlorthalidone T1/2 = 40 hr; indapamide T1/2 = 26 hrs; Hctz T1/2 = 5.6 – 14 hrs Resistant hypertension is felt due to occult volume expansion/inadequate

105 Refractory Hypertension
Hard to Treat Hypertension Refractory Hypertension Five or more medications including a long acting diuretic AND a mineralocorticoid receptor antagonist In the context of normal renal perfusion, felt to be a neurogenic cause Long acting thiazides – chlorthalidone T1/2 = 40 hr; indapamide T1/2 = 26 hrs; Hctz T1/2 = 5.6 – 14 hrs

106 Hypertension Case Studies #2
45 YO Female with resistant HTN for f/u Meds: hctz 25mg qd; lisinopril 40 mg BID; amlodipine 7.5 mg qd; simvastatin 40 mg qd PMHx – chronic htn; prediabetes, LDL, 1-2 beers/d. Hypokalemia. BP 156/98 P=82 R=16/min BMI 29.5 Serum aldosterone/plasma renin activity ratio of 31ng/dL per ng/mL/hr (nl <23.6) Aldosterone-to-renin ratio (ARR) is the mass concentration of aldosterone divided by the plasma renin activity in blood plasma. The aldosterone/renin ratio is recommended as screening tool for primary hyperaldosteronism. On average, an ARR cutoff of 23.6 ng/dL per ng/(mL·h) has been estimated to have a sensitivity of 97% and specificity of 94%.[3] An ARR value in an individual that is higher than the cutoff indicates primary hyperaldosteronism.

107 What is most likely diagnosis?
Hypertension Case Studies #2 What is most likely diagnosis? A. Primary hyperaldosteronism B. Pheochromocytoma C. Hemochromatosis D. Alcohol Induced hypertension E. Addison’s disease Correct Answer – A. Conn Syndrome. Treatment resistant Hypertension, unprovoked hypokalemia, depressed plasma renin activity. Most commonly due to unilateral aldosterone-producing adenoma. Associated with muscle weakness, intermittent paralysis, headaches, palpitations, polydipsia, polyuria, nocturia. Femal:male 2:1. Typically diagnosed between age Present in approximately 1% of unselected hypertensive patients.

108 Resistant Hypertension Case Studies #2
Initially consider: Nonadherence to medications Drug induced hypertension White coat hypertension Inaccurate BP measurements Lifestyle issues (weight, Na, alcohol) Missed medical diagnoses

109 What is most likely to help?
Hypertension Case Studies #2 What is most likely to help? A. Candesartan (Atacand) B. Diltiazem (Cardizem) C. Spironolactone (Aldactone) D. Alcohol abstinence E. Discontinuing simvastatin Correct Answer: Spironolactone

110 Hypertension Case Studies #3
52 YO White female avid scuba diver presents with stage 1 hypertension. 152/94 P=65 R=16/min BMI-23 Regular exercise and history of mild hypercholesterolemia treated with diet. Given the following EKG which meds would be safe to use?

111 Hypertension Case Studies #3
First Degree AV Block – Not a contraindication to the use of beta blockers or nondihydropyridine CCBs. BBs and nonhydropyridine CCBs slow conduction through the AV node and should NOT be used in pts with 2nd or 3rd degree heart block. However rate limiting drugs should be used with extreme caution in scuba divers!

112 Hypertension Case Studies #3
Amlodipine Diltiazem Atenolol Clonidine Chlorthalidone ACE-I / ARB BBs and nonhydropyridine CCBs slow conduction through the AV node and should NOT be used in pts with 2nd or 3rd degree heart block. However rate limiting drugs should be used with extreme caution in scuba divers!

113 Hypertension Case Studies #4
68 YO African American male with presents with refractory hypertension presents with a history of slowly progressive confusion, irritability and forgetfulness over the last few weeks. He is otherwise active, walks his dog daily and has had no other health issues. 146/88 P=78 R=16/min BMI-27 His labs including glucose, electrolytes, LFTs, CBC, are normal. Neurologic exam normal except cognitive slowing and poor short term memory. Which three of the following drugs most likely are contributing to his altered mental status?

114 Hypertension Case Studies #4
Methyldopa (Aldomet) Propranolol (Inderal LA) Nifedipine (short acting) Spironolactone Chlorthalidone Lisinopril The risk of cognitive impairment remains low for such drugs as diuretics and ACEIs. Correct Answer – 1st three

115 Hypertension Case Studies #5
69 YO white female with BP 160/84. Medical Hx notable for osteoporosis and calcium oxalate kidney stones. Which of the following drugs would be most appropriate for managing this patient’s hypertension?

116 Hypertension Case Studies #5
A. An ACE Inhibitor B. An alpha-1 agonist C. A β-blocker D. A calcium channel blocker E. A Thiazide diuretic F. A mineralocorticoid receptor blocker Correct Answer – E. Thiazides, CCB, ACEI, ARBs yielded comparable effects on overall mortality and CV, CBV, and kidney outcomes. A notable exception was heart failure improved with thiazides. Thiazide diuretics can be used as an intervention for calcium oxalate stones. Thiazides may preserve bone density and raise blood calcium levels (whereas loop diuretics can decrease serum calcium.

117 2017Hypertension Update J. Paul Martin, MD

118 Studies ACCORD: Action to Control Cardiovascular Risk in Diabetes Trial 2008 – intensive BP management in diabetics didn’t improve outcome of nonfatal CV events ALLHAT: Antihypertensive Lipid Lowering Treatment to Prevent Heart Attack Trial demonstrated that chlorthalidone is superior to ACEI, CCB, Alpha –blocker

119 Studies 3. HYVET: HYpertension in the Very Elderly Trial 2008 – All cause mortality reduction 21%; using indapamide/perindopril 3845 patients >80 yrs w systolic BP > PROGRESS: Perindopril pROtection aGainst REcurrent Stroke Study 2001 demonstrated benefit of ACEI and a thiazide (indapamide). Perindopril = Aceon

120 Studies REACH: REduction of Atherothrombosis for Continued Health registry 45,000 patients: JAMA. 2012;308[13]: Among patients with either coronary artery disease (CAD) risk factors only, known prior heart attack, or known CAD without heart attack, the use of beta-blockers was not associated with a lower risk of a composite of cardiovascular events that included cardiovascular death, nonfatal heart attack or nonfatal stroke.

121 Studies ONTARGET: ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial 2008: Telmisartan (Micardis) was equivalent to ramipril (Altace) with less angioedema. The combination provided no benefit, but more adverse effects. Telmisartan (Micardis) was equivalent to ramipril (Altace) in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number,

122 Studies ACCOMPLISH trial: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension 2008 The benazepril–amlodipine combination was superior to the benazepril–hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. Despite the similar blood pressure, the combination with the calcium-channel blocker and ACE inhibitor reduced cardiovascular morbidity and mortality 20%. benazepril 40mg plus amlodipine 5mg daily benazepril 40mg plus hydrochlorothiazide 12.5mg daily

123 Studies COMMIT : ClOpidogrel and Metoprolol in Myocardial Infarction Trial 2005 (China: 46,000 patients) No benefit of Metoprolol over placebo to composite of death, cardiac arrest or death from any cause during the scheduled treatment period. The use of early β-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation by 0.5%, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting β-blocker therapy in hospital only when the hemodynamic condition after MI has stabilized.


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