Hypertension: Which drugs to choose for patients with cardiovascular disease

,

Applied Evidence

Hypertension: Which drugs to choose for patients with cardiovascular disease

J Fam Pract. 2006 April;55(4):291-298

PDF Download

References

1. American Heart Association. Heart Disease and Stroke Statistics–2004 Update. Dallas, Tex: American Heart Association, 2003.

2. Ogden LG, He J, Lydick E, Whelton P. Long-term absolute benefit of lowering blood pressure in hypertensive patients according to JNC VI risk stratification. Hypertension 2000;35:539-543.

3. Hansson L, Lindholm L, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999;354:1751-1756.

4. Turnbull F. Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials. Lancet 2003;362:1527-1535.

5. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-1913.

6. Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001;345:1291-1297.

7. Whelton P, He J, Appel L, et al. National High Blood Pressure Education Program Coordinating Committee. Primary prevention of hypertension: Clinical and public health advisory from the National High Blood Pressure Education Program. JAMA 2002;288:1882-1888.

8. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.

9. Pfeffer MA, Braunwald E, Moye LA, et al. The SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669-677.

10. Flather MD, Yusuf S, Kobler L, et al. ACE-Inhibitor Myocardial Infarction Collaboration Group. Long-term ACE inhibitor therapy in patients with heart failure or left ventricular dysfunction: A systematic overview of data from individual patients. Lancet 2000;355:1575-1581.

11. Chobanian A, Bakris G, Black H, et al. Seventh Report of The Joint National Committee on Prevention, Detection, Evaluation, and Management of High Blood Pressure (JNC-7). Hypertension 2003;42:1206-1252.

12. Hunt S, Abraham WT, Chin M, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart failure in the Adult. A report of the American College of Cardiology/American Heart Association task force on practice guidelines. Writing to update the 2001 guidelines for the evaluation and management of heart failure, 2005, available at www.acc.org, accessed 10-19-05.

13. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomized trial. Lancet 2001;357:1385-1390.

14. Packer M, Coats A, Fowler MB, et al. Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-1658.

15. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-2007.

16. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patents with severe heart failure. Randomized Aldactone Evaluation Study (RALES) Investigators. N Engl J Med 1999;341:709-717.

17. Pitt B, Remme WJ, Zannad F, et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival (EPHESUS) Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;14:1309-1321.

18. Beta-Blocker Heart Attack (BHAT) Research Group. A randomized trial of propranalol in patients with acute myocardial infarction, I: mortality results. JAMA 1982;247:1707-1714.

19. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981;304:801-807.

20. Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT Study: a randomized controlled trial. JAMA 2004;292:2217-2226.

21. The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med 2000;342:145-153.

22. The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease; randomized, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782-788.

23. PROGRESS Collaborative Group. Randomised trial of a perindopril based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischemic attack. Lancet 2001;358:1033-1041.

24. CIBIS Investigators and Committees. A randomized trial of beta blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1994;90:1765-1773.

25. Brassuer L. Experts challenge present hypertension guidelines. Intern Med 2005;6:1-and 8.-

26. Hyman DJ, Pavlik VN. Self-reported hypertension treatment practices among primary care physicians: Blood pressure thresholds, drug choices, and the role of guidelines and evidence based medicine. Arch Intern Med 2000;160:2281-2286.

27. Poole-Wilson P, Swedberg K, Cleland J, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomized controlled trial. Lancet 2003;362:7-13.

28. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial. The Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-1587.

29. Cohn JN, Tognoni G. Valsartan Heart Failure Trail (VAL-HEFT) Investigators. A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-1675.

30. Young JB, Dunlap ME, Pfeffer MA, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation 2004;110:2618-2626.

31. The PEACE Trial Investigators. Angiotensin-converting enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058-2068.

32. Kober L, Torp-Pedersen, Carlsen JE, et al. for the TRACE study group. A clinical trial of the angiotensin-converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial dysfunction. N Engl J Med 1995;333:1670-1676.

33. Ambrosioni E, Borghi C, Magnani B. For the SMILE Study Group. The effect of the angiotensin-converting enzyme inhibitor zofenopril on mortality and morbidity after myocardial infarction. N Engl J Med 1995;332:80-85.

34. Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Fam Pract 2004;53:111-120.

The Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)¹⁵ concluded that the addition of extended-release metoprolol (Lopressor, a β₁-adrenergic receptor blocker) for patients with heart failure demonstrated a survival benefit when compared with patients not receiving a beta-blocker (LOE: 1). One of the essential elements of this trial was the ability to achieve a dose of 200 mg of metoprolol a day. Frequently in clinical practice low-dose or even homeopathic doses are used with few data to support such use.

The Carvedilol or Metoprolol European Trial (COMET)²⁷ of patients with heart failure suggested that nonselective neurohumoral (β and α) blockade may increase the benefit in comparison with selective β₁-blockade (LOE: 1). There has been significant debate regarding the dose and the formulation of the drugs in COMET, but we advocate using doses and drug formulations that were specifically in the large prospective randomized trials (CIBIS II, the carvedilol trials, and MERIT-HF).

Angiotensin receptor blockers

Prescribe an ARB only when a patient cannot tolerate an ACE inhibitor secondary to cough or hyperkalemia.¹² As these are generally used after or as an adjunct to ACE inhibitors, the usual dose is similar to that for blood pressure dosed twice daily. If patients do not tolerate ACE inhibitors, theses doses may also be higher than those used for blood pressure response alone.

The evidence. The Losartan Heart Failure Survival Study (ELITE II)²⁸ demonstrated the benefit of the ARB losartan (Cozaar) in the treatment of heart failure, but not superiority over previously used ACE inhibitors (LOE: 1). In addition, there was no difference in renal insufficiency with one drug class compared with another. Researchers concluded that ARBs should be used only for patients intolerant to ACE inhibitors.

The Valsartan Heart Failure Trial Investigators Study (Val-HeFT)²⁹ randomized 5010 patients to receive valsartan (Diovan) or placebo combined with standard therapy (ACE inhibitors and beta-blockers) (LOE: 1). The ARB group demonstrated a 13.2% greater reduction than placebo in the combined endpoint of morbidity and mortality (as defined by incidence of cardiac arrest and resuscitation, hospitalization for heat failure, or administration of intravenous inotropes or vasodilators for a minimum of 4 hours). However, a post-study review²⁹ of patients who received the ARB, ACE inhibitor, and beta-blocker combination showed increased mortality.

In 2004, the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity trial (CHARM)³⁰ found that when the ARB candesartan (Atacand) was added to standard therapy (ACE inhibitor, beta-blockers, aldosterone antagonist) there was a 33% reduction in all-cause mortality, similar to that found with beta-blockers and ACE inhibitors) (LOE: 1). In addition, the CHARM group found no increased risk when candesartan was combined with other treatments; it concluded that ARBs could be added to regimens for all patients with heart failure unless a contraindication exists.

The American College of Cardiology/American Heart Association guidelines prefer ACE inhibitors over ARBs, and recommend ARBs be used when an ACE inhibitor is not tolerated or if there are other contraindications. A low level of evidence (2b) suggests that an ARB may be added to conventional medical therapy with an increased risk of renal insufficiency and hyperkalemia (SOR: A).¹²

Potassium-sparing diuretics

Aldosterone antagonists are appropriate for patients with heart failure (SOR: A), though we recommend working in conjunction with a cardiologist to minimize complications and to insure that a complete heart failure plan is in place (SOR: C). Spirinolactone (Aldactone, Aldactazide) is used for physiologic purposes (as a neurohormonal regulator) and is not used for blood pressure control. Most heart failure specialists begin with a dose of 12.5 mg/d and advance to doses utilized in the clinical trials (25–50 mg/d).

The evidence. Potassium-sparing diuretics lower mortality among heart failure patients. Spironolactone works in part by reducing aldosterone levels and increasing serum potassium.

In the Randomized Aldactone Evaluation Study (RALES),¹⁶ patients with severe heart failure (ejection fraction <35%) on standard medical therapy were randomized to receive spironolactone or placebo (LOE: 1). The spironolactone group exhibited a 30% reduction in mortality compared with conventional medical therapy, and the study was ended early at 24 months.

FAST TRACK

Potassium-sparing diuretics lower mortality among heart failure patients; make a plan with a cardiologist to help minimize complications

In the Eplerenone Post Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS),¹⁷ an overall reduction in death of 8%, a decrease of sudden cardiac death by >20% (relative risk reduction), as well as an overall reduction of hospitalization for heart failure of 15% occurred in the eplerenone (Inspra) group (LOE: 1) (NNT to save 1 life in 1 year=50).