Management of Hypertension

1. Management of Hypertension Laura Fitzpatrick, MD, MPH Intern Academics Friday the 13th, August 2004

2. Background • The JNC VII guidelines are issued periodically from the National Heart, Lung, and Blood Institute. (NHLBI) • Many new observational studies and clinical trials since JNC VI in 1997. • JNC VII published in 2003: express format in JAMA, full report in Hypertension.

3. What are the differences between JNC VI and JNC VII? • A new category added called “pre-hypertension”; this combines normal and borderline. • Previous stage 2 and 3 were combined. • Lower threshhold for starting therapy.

4. Blood pressure classifications

5. BP increases with age

6. How does one measure BP? • Auscultatory method • Person seated at least 5 min with feet on the floor, arms supported at heart level. • Use a cuff bladder that encircles at least 80% of the arm to ensure accuracy.

7. What are the target organs of injury? • Cardiac: LVH, angina, CAD, CHF • Neuro: CVA/TIA • Renal: CKD • PVD • Retinopathy

8. What components of history are important in a newly diagnosed pt? • h/o smoking • h/o hyperlipidemia • physical activity • h/o diabetes • age • family history of premature CAD defined as males < 55 and females < 65

9. What PE components should be performed in a newly diagnosed pt? • checking BP in both arms • examination of the optic fundi • documenting the BMI • listening for carotid, abdominal, and femoral bruits • palpating the thyroid • detailed cardiac/pulmonary exam • assessing for enlarged kidneys on abdominal exam • documenting peripheral pulses • neurologic exam

10. What labs should we obtain? • EKG • U/A • glucose • hematocrit • K+ • creatinine • Calcium • Lipid profile • optional: albumin/creatinine ratio or urinary albumin excretion

11. What is the goal BP in patients with hypertension? • Goal is <140/90 • In patients with DM or CKD, goal is <130/80 • In patients with >1g proteinuria, the goal is <125/75

12. When do you follow up?

13. Why these goals? • HOT (Hypertension Optimal Treatment) Trial. • The National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines. • ADA recommendations

14. Hypertension Optimal Treatment Trial (HOT) • Goal was to determine the optimal level of BP to reduce CV morbidity/ mortality. ? J-curve existence. • Randomized 19,000 pts with HTN (mean 170/105 mm Hg) to 3 different goal diastolic bp arms: <= 90, <= 85, <= 80 mm Hg. • Felodipine 5 mg was given as baseline therapy, with addition of other agents according to a 5-step regimen. • Half were randomized to receive aspirin.

15. Hypertension Optimal Treatment Trial (HOT) • DBP was reduced to 85.2, 83.2, and 81.1 mm Hg. • Outcomes: CV events, MI, CVA, CV mortality, total mortality. • No significant differences among the 3 arms with respect to any outcome.

17. Hypertension Optimal Treatment Trial (HOT) • Trial did not prove/ disprove the J-curve. • Lower bp further did not appear to enhance risk. • ASA 75 mg significantly reduced MI and CV events (by 15%). Lancet 1998 Jun 13;351(9118):1755-62

18. What are the lifestyle modifications suggested by the JNC VII? • weight loss to BMI 18-24 (decrease of 5-20 mm Hg for every 10 kg wt. loss) • DASH diet rich in potassium and calcium (lead to 8-14 mm Hg reduction in SBP) • limit Na intake (a 2.4 g Na diet lead to 2-8 mm Hg reduction in SBP) • physical activity at least 30 min/day 7 days a week (lead to 4-9 mg Hg reduction in BP) • limit etoh intake

19. What are the different classes of BP lowering medications available? • Thiazides • Other diuretics (loop, K+ - sparing) • Beta-blockers • Combined alpha and beta- blockers (carvedilol, labetalol) • ACE inhibitors • Angiotensin-receptor blockers • CCB’s (non-dihydropyridine) – verapamil, dilt • CCB’s (dihydropyridines) – amlodipine, felodipine • Central-acting agents • Direct vasodilators

20. What to use when

21. What to use when

22. Congestive Heart Failure • SOLVD (1991) • randomized pts with CHF-EF<35% to enalapril vs. placebo and followed for 41 months. • 16% risk reduction in mortality (p=.0036) • 26% risk reduction for hospitalization (p<.0001) • XSOLVD showed that this gap narrowed over time. N Engl J Med 1991 Aug 1;325(5):293-302

23. Congestive Heart Failure • MERIT-HF (1999) • ~4000 patients with class II-IV CHF and EF<40% randomized to metoprolol XL/CR vs. placebo. Followed for ~1 yr. • All-cause mortality lowered with metoprolol (RR=0.66) • Also decreased sudden deaths, deaths from worsening heart failure, and hospitalization. • Study terminated prematurely. Lancet 1999 Jun 12;353(9169):2001-7

24. Congestive Heart Failure • United States Carvedilol Heart Failure Program (NEJM, 1996) • 1100 pts already receiving dig, diuretics, ACE randomized to carvedilol vs. placebo. • Decreased total mortality • Decreased hospitalizations • Increased event-free survival • Study terminated prematurely N Engl J Med 1996 May 23;334(21):1349-55

25. Ischemic Heart Disease • SAVE trial (1992) • 2231 patients with EF<40% but no overt HF signs/symptoms, 3-16 days post-MI randomized to placebo vs. captopril. • All-cause mortality decreased 19% (P=.019) • Major CV events decreased 21% • Recurrent MI decreased 25% N Engl J Med 1992 Sep 3;327(10):669-77

26. Cerebrovascular Disease • SHEP (Systolic HTN in the Elderly, 1991) • 4736 pts 60 yrs and over with isolated systolic HTN (mean 170/77) randomized to chlorthalidone vs. placebo. Atenolol added, if needed, to achieve a goal reduction of 20 mmHg. • Primary outcome: CVA; Secondary: CV M/M, all-cause mortality, QOL measures. JAMA 1991 Jun 26;265(24):3255-64

27. SHEP trial • Outcomes • Risk of stroke significantly lower in the treatment group. (RR=0.64; p=.0003) • Risk of CV events was reduced, but NS.

28. High-risk for coronary disease • LIFE (2002) • Randomly assigned 9193 pts with severe HTN and EKG evidence LVH to losartan vs. atenolol. • Outcomes were death, MI or stroke. • RR of primary composite endpoint was 0.87 (p=.021) • Decreased stroke RR=0.75 (p=.001) Lancet 2002 Mar 23;359(9311):995-1003

29. LIFE trial

30. LIFE trial

31. High-risk for coronary disease • HOPE (2000) • 9451 high-risk pts without acute MI, HF or LV dysfunction. • High-risk: either evidence of vascular disease OR diabetes + another CV RF. • Pts randomly assigned to ramipril vs. placebo. • Endpoints were CV death, MI, or CVA N Engl J Med 2000 Jan 20;342(3):145-53

32. HOPE trial • Study terminated after a 4.5 year follow-up when it showed the following: • Reduction in primary endpoint (RR=0.78) • Reduction in nonfatal MI (RRR=23%) • Reduction in Stroke (RR=0.68)

33. HOPE trial

34. ALLHAT • A RCT of high-risk pts with HTN, designed to determine if occurrence of fatal CHD or nonfatal MI is lower with a CCB, ACE-I, alpha-blocker vs. thiazide diuretic. • Secondary outcomes included all-cause mortality, CVA, and CVD events. • A subtrial included moderately hyperlipidemic patients randomized to pravastatin vs. placebo to determine differences in mortality.

35. ALLHAT • 42,000 patients >55 years (men and women) with stage 1 or 2 HTN and >=1 additional CVD risk factor. • Randomized to 4 arms: tx with amlodipine, chlorthalidone, lisinopril or doxazosin. Goal: <140/90 • Doxazosin arm discontinued due to higher rates of CVD and CHF.

36. ALLHAT • Patient population was diverse • Mean age: 67 years • 36% had diabetes • 47% female • 35% black • 19% Hispanic • Populations virtually identical at baseline

37. ALLHAT results

38. ALLHAT results • No significant difference among the 3 arms with respect to the primary outcome. • The amlodipine group had a 38% higher risk of CHF compared with chlorthalidone group. (p<.001) • Lisinopril group had a 15% higher risk of CVA (p=.02), a 10% higher risk of combined CVD (p<.001); 19% higher risk of HF. • The efficacy of chlorthalidone compared to lisinopril was higher in blacks than in whites.

39. Secondary HTN

40. What are the identifiable causes of HTN? • chronic kidney disease • aortic coarctation • cushing syndrome/ chronic steroid therapy • drug-related (ex. Cocaine, amphetamines, decongestants) • Pheochromocytoma • primary aldosteronism • renovascular hypertension • sleep apnea • thyroid/ parathyroid disease

41. When is a workup of secondary HTN appropriate? • In patients whose history, PE, severity of HTN or initial labs suggest secondary causes • BP responds poorly to drug therapy • BP begins to increase without explanation after being well-controlled • Onset of HTN is sudden

42. Cases • A 54 y.o. WF with PMH of HTN, fibromyalgia, recently diagnosed type 2 DM presents for her regular diabetes visit. Baseline EKG shows no abnormalities, and urinary dipstick showed trace proteinuria. Her bp is 147/92, and her current regimen consists of HCTZ 12.5 mg daily and atenolol 50 mg daily. • (1) What is her goal bp? • (2) What is the next step in the management of her bp? • (3) What agents would you consider if the EKG had shown evidence of LVH? • (4) You place her on ramipril, and her creatinine bumps from its baseline of 1.2 to 1.5, where it stabilizes. Do you stop the ACE-I?

43. Answers • (1) What is her goal bp? 130/ 80 in a patient with DM. Her trace proteinuria is not likely to exceed 1g/day, but if it did, her goal would be 125/ 75 mm Hg. • (2) What is the next step in the management of her bp? Add another agent. You could titrate up one of her existing medications, however, given her proteinuria you should consider the addition of an ACE-I or ARB. • (3) What agents would you consider if the EKG had shown evidence of LVH? You could consider an ARB (or ACE-I). The LIFE trial compared losartan and atenolol in hypertensive patients with LVH; losartan was superior, mainly due to its reduction of stroke risk. • (4) Serum creatinine should be carefully monitored with ACE-I initiation, but creatinine increases up to 35% are acceptable. Increases over 20% may be a clue to the presence of renal artery stenosis.

44. Cases A 48 y.o. WM presents to your office with no significant PMH. His bp is 168/92. This has been confirmed on two other separate occasions. He is on no meds at present. He has no DM, no known heart disease, no history of CVA/ TIA. His family history is unremarkable. He does not smoke, and drinks minimal alcohol. (1) What class of hypertension does he have? (2) How would you manage his blood pressure? (3) What labs would you order now?

45. Answers (1) What class of hypertension does he have? He has stage 2 hypertension, as his systolic value places him in that category. (2) How would you manage his blood pressure? Start 2 agents. HCTZ would be a good choice for one of the agents. (3) What labs would you order now? 12-lead EKG, fasting lipid panel, glucose, serum Cr and U/A. A Hct and electrolytes may be helpful.

46. Cases • A 87 y.o. AAM has never visited a physician in his life and comes to see you. His bp is 180/75. He states he has never had any health problems. Your workup of target end-organ damage, along with all bloodwork, is completely negative. • (1) Would you start 1 or 2 agents? • (2) What would be the first agent you would choose and why?

47. Answers • (1) Would you start 1 or 2 agents? Although he falls under the category of stage 2 HTN (and therefore needs to be started on 2 agents), given his advanced age (and likely decreased metabolism), you could consider starting 1 agent, then bringing him back soon (within 2-4 weeks) to start a second agent. Ultimately, he will very likely need 2 agents. • (2) What agent(s) would you choose and why? According to the SHEP trial, elderly patients with isolated systolic HTN had a significant decrease in stroke risk when patient were placed on chlorthalidone. You could therefore consider a thiazide diuretic as initial therapy.