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

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Antihypertensive drugs in heart failure

Angiotensin-converting enzyme inhibitors

Give all patients with heart failure an ACE inhibitor, if clinically tolerated (SOR: A). Although blood pressure control is very important to treat the physiology and neurohormonal basis of heart failure, the primary reason to use ACE inhibitors (as well as other medications) is to provide a disease modifying intervention and treat blood pressure when it is elevated. Different disease conditions require different doses to achieve the desired goal. With heart failure, the dose of an ACE inhibitor is given twice daily at typically 2 to 3 times the dose of that used for hypertension.

The evidence. In 1991, the Studies of Left Ventricular Dysfunction (SOLVD) trial⁸ demonstrated a 26% risk reduction for death or hospitalization due to heart failure (95% confidence interval [CI], 18–34) for those treated with the ACE inhibitor enalapril (Vasotec) (LOE: 1). The following year, the Survival and Ventricular Enlargement (SAVE)⁹ trial demonstrated a risk reduction of 19% for patients with a reduced ejection fraction after myocardial infarction (MI) when the ACE inhibitor captopril (Capoten) was used (LOE: 1).

The calculated NNT with an ACE inhibitor to save 1 life over 1 year is 43.¹⁰ (See TABLE W2 for a summary of clinical trials and levels of evidence.) The TABLE in this article summarizes treatment recommendations based on these studies.^8-23

TABLE
Drugs of choice for hypertension and various comorbidities

TREATMENT RECOMMENDATIONS BASED ON STUDIES/GUIDELINES	SOR
Congestive Heart Failure
ACE inhibitor should be used in patients with heart failure unless a contraindication exists^8,9,11,12	A
Beta-blockers should be used in patients with heart failure unless a contraindication exists^11-15	A
ARB should be used in heart failure if patient is intolerant to ACE inhibitor¹²	A
Aldosterone antagonists should be used in patients with severe heart failure unless a contraindication exists^16,17	A
Aldosterone antagonists should be prescribed in consultation with a cardiologist	C
Coronary Artery Disease
Beta-blockers should be used in patients post-MI unless a contraindication exists^11,13,18,19	A
CCB should be used in patients with stable coronary artery disease unless a contraindication exists^11,20	A
ACE inhibitors should be used in patients with stable coronary artery disease and no left ventricular dysfunction unless a contraindication exists^11,21,22	A
Stroke
ACE inhibitor and indapamide should be used in patients with a TIA or stroke unless a contraindication exists^11,23	B
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; MI, myocardial infarction; SOR, strength of recommendation; TIA, transient ischemic attack

Beta-blockers

Give a beta-blocker, if tolerated, to patients in heart failure (SOR: A). Dosing has been determined by clinical trial data. In general, in order to significantly impact morbidity and mortality in congestive heart failure, the patient needs to reach a dose of 150 mg of metoprolol XL a day or 6.25 mg to 12.5 mg of carvedilol given twice daily. Ideal doses are greater than 200 mg/d of metoprolol XL or 25 mg twice daily of carvedilol.

FAST TRACK

Patients with heart failure should take an ACE inhibitor, typically at doses 2 to 3 times that used for hypertension

The evidence. The Cardiac Insufficiency Bisoprolol Study (CIBIS),²⁴ published in 1994, was a randomized, placebo-controlled, double-blind trial designed to test the efficacy of beta-blockade in the treatment of heart failure (LOE: 1). Although no difference in mortality was demonstrated between intervention and control groups, the intervention group showed improved functional status.

The Carvedilol Post Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN)¹³ trial (LOE: 1) evaluated patients with left ventricular dysfunction or heart failure after an MI, while the Carvedilol Prospective Randomized Cumulative Survey (COPERNICUS)¹⁴ group (LOE: 1) enrolled only patients with severe heart failure (ejection fraction <25%, NYHA class III and IV). These studies demonstrated an overall decrease in cardiovascular morbidity and mortality, as well as all-cause mortality for patients with heart failure receiving the nonspecific beta-blocker carvedilol (Coreg) (receptor blockade at β₁, β₂, α₁). CAPRICORN produced an overall risk reduction in mortality of 2% to 3% at 1 year, resulting in the same NNT (43) over 1 year as ACE inhibitors.¹³ This is the only beta-blocker tested after infarction to demonstrate a mortality difference for patients with heart failure or decreased left ventricular dysfunction (ejection fraction <40%).

Taking JNC-7 to heart

Hypertension specialists debate about how to approach the hypertensive patient. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Management of High Blood Pressure (JNC-7) guidelines¹¹ call for defined goals in lowering blood pressure and a stepwise selection of drugs based on comorbidities.

Some leading hypertension experts say this is too formulaic. Dr Michael Alderman, Professor in the Department of Medicine and Epidemiology and Population Health at the Albert Einstein School of Medicine, argues “we have to get over the limitation of the straightjacket of numbers to define our actions.”²⁵ He further asserts that “our willingness to drive blood pressure down has to be modulated by the risk the patient has and the price one has to pay to lower it. A 30% reduction in risk does not mean much if your risk is low, but if your risk is high it means a lot.”²⁵ As such, Dr Alderman argues we should base treatment decisions on “total risk” and not the level of blood pressure. Other leaders in the field such as Mathew Weir, MD, director of the Division of Nephrology, University of Maryland, and Richard Devreaux, MD, Professor of Medicine, Division of Cardiology, Cornell University Medical Center, agree with this more individualized approach.²⁵

But understanding the basic formula is what helps us innovate. In general, we agree that individualizing patient care is the ideal, and that some patients may not tolerate “recommended” treatment. However, it is not possible for physicians to individualize care (a highly complex undertaking) when they still lack understanding at the basic level of care. With the poor treatment of hypertension in the US, we believe that guidelines such as JNC-7 are essential to improving blood pressure control.

Hyman and Pavlik²⁶ demonstrated that physician factors, especially lack of awareness of hypertension treatment recommendations, correlate with poor hypertension treatment. In their 2001 study that included 1200 primary care physicians, 41% of physicians were not familiar with or had not heard of the recommendations. This finding was not trivial. The importance of familiarity with JNC-7 guidelines was demonstrated when statistical analysis revealed that a working knowledge of these guidelines significantly increased adherence with published recommendations (including blood pressure control). As such, it would appear that not following the guidelines has less to do with disagreements over treatment options and more to do with understanding the value of the guidelines to basic management.