Hypertension: Which drugs to choose for patients with cardiovascular disease

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Applied Evidence

Hypertension: Which drugs to choose for patients with cardiovascular disease

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

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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.

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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.

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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.

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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.

It is worth noting that the doses used in these studies were devised to alter neurohumoral regulation, and are not to be used as significant diuretics. To date, no comparative study between spironolactone and eplerenone has been undertaken.

Coronary artery disease

Beta-blockers

Prescribe a beta-blocker for every post-MI patient without severe heart block or cardiogenic shock (SOR: A).

The evidence. The Beta-Blocker Heart Attack Trial (BHAT),¹⁸ sponsored by the National Heart, Lung, and Blood Institute, was designed to evaluate the benefits of the beta-blocker propranolol (Inderal) after MI (completed more than 24 years ago, before modern medical therapy) (LOE: 1). Total mortality during the average 24-month follow-up period was 7.2% in the propranolol group and 9.8% in the placebo group. The incidence of nonfatal reinfarction was decreased by 15.6% in the treatment group.

A similar trial completed in the early 1980s was The Norwegian Multi-Center Study.¹⁹ This trial, which assessed the efficacy of timolol (Blocadren, Timolide) after MI, demonstrated a 44.6% reduction in sudden cardiac death (LOE: 1). The study group reached the same conclusion as the BHAT researchers, and recommended that beta-blockers be used following an MI to reduce reinfarction and death.

Angiotensin-converting enzyme inhibitors

Use ACE inhibitors only for stable post-MI patients without decreased left ventricular function.

FAST TRACK

Stable patients without lowered left ventricular function can take an ACE inhibitor or calcium channel blocker in addition to a beta-blocker

The evidence. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial³¹ evaluated the benefit of using an ACE inhibitor for patients with stable coronary artery disease and slightly reduced ejection fraction (>40%) (LOE: 1). There was no statistical difference in the primary endpoint (cardiac-induced death, MI, or need for revascularization) between the treatment group (21.9%) and the placebo group (22.5%).

Contrary to the findings of the PEACE trial, many other studies have shown that ACE inhibitors are beneficial for patients with coronary artery disease. In the Trandolapril Cardiac Evaluation (TRACE) study,³² patients stabilized after acute MI were randomized to receive the ACE inhibitor trandolapril (Mavik) or placebo on days 3 to 7 following infarction (LOE: 1). In the treatment group, risk of death from all causes declined 17.6%, risk of death from cardiovascular causes fell 21%, and progression to severe heart failure decreased 27%. These post-MI benefits are also supported by results of the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) study (LOE: 1).³³

The Heart Outcomes Prevention Evaluation Investigators (HOPE)²¹ (LOE: 1), and the European Trial on Reduction of Cardiac Events with Perindopril in Patients with Coronary Artery disease (EUROPA)²² (LOE: 1), demonstrated the benefits of ACE inhibitors in reducing cardiovascular events for patients with or at risk for coronary artery disease, but with normal left ventricular function. The HOPE study showed a significant reduction of events with the ACE inhibitor ramipril (Altace) (NNT=1000 patients over 4 years, resulting in a decrease of 150 events for 75 patients), whereas EUROPA demonstrated the results for the ACE inhibitor perindopril (Aceon) (NNT=50 patients over 4 years to prevent 1 major cardiovascular event).

Calcium channel blockers

Use calcium channel blockers only for stable post-MI patients without decreased left ventricular function or heart failure.

The evidence. The Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT)²⁰ study compared treatment using a calcium channel blocker (amlodipine) and an ACE inhibitor (enalapril) with placebo for normotensive patients with coronary artery disease (LOE: 1). Amlodipine reduced hospitalization for angina by 42.2%, nonfatal MI by 26%, and stroke or transient ischemic attack by 50.4% (NNT=16). The study group concluded that the use of the ACE inhibitor enalapril showed “directionally similar, but smaller and nonsignificant, treatment effects.”²⁰ There was no reduction in overall mortality.

Stroke

Prescribe the combination of perindopril and indapamide for all patients with a history of stroke or transient ischemic attack, regardless of blood pressure (SOR: B).

FAST TRACK

Perindopril and indapamide reduce risk of stroke by 43% in patients who have had a stroke or transient ischemic attack

The evidence. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS)²³ was designed to evaluate the benefits of the ACE inhibitor perindopril (with the addition of indapamide at the physician’s discretion) for patients with or without hypertension who have had a transient ischemic attack or stroke (LOE: 1). Perindopril plus indapamide reduced risk of stroke by 43%, but treatment with a single agent showed risk reduction.

Search strategy

To see which drug classes are most often recommended in the treatment of hypertension based on underlying cardiovascular disease, we performed an initial Medline search using the key words hypertension and cardiovascular disease. This was supplemented with a search of the archives of the journals Circulation, Hypertension, Stroke, and the authors’ personal references.

All studies were evaluated using the Strength of Recommendation Taxonomy.³⁴ Strength of recommendation (SOR) evaluates a study based on patient (not disease) oriented outcomes, and level of evidence (LOE) is based on key outcomes as well as the methodology of the study.