Challenges abound in management, treatment of patients with hypertension, CAD

For patients with CAD, it is vitally important to keep BP under control. The combination of CAD and uncontrolled hypertension raises the risk for a variety of cardiac events, particularly stroke. However, there has been much debate surrounding the extent to which BP should be controlled because there can be consequences for targets that are too low.

The release of a new scientific statement from the American Heart Association, American College of Cardiology and American Society of Hypertension, “Treatment of Hypertension in Patients with Coronary Artery Disease,” may put some of that debate to rest. After reviewing the literature, the statement writing group determined that all patients with hypertension and CAD should be treated to a BP goal of less than 140/90 mm Hg, and that a target of less than 130/80 mm Hg may be appropriate in certain high-risk patients with heart disease. Beta-blockers are an important first-line therapy in this population, according to the statement.

The new recommendations are a welcome update in light of controversy surrounding the report released by the panel convened for the Eighth Joint National Committee (JNC 8), which recommended that adults aged at least 60 years without diabetes or chronic kidney disease be treated to a BP target of less than 150/90 mm Hg, Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, said in an interview.

“The most prevalent dyad in our Medicare population is the combination of hypertension and CAD. This new AHA/ACC/ASH document makes it very clear that for patients with CAD, regardless of age, that the treatment threshold and target is less than 140/90 mm Hg. This panel reaffirmed the [Seventh Joint National Committee (JNC 7)] treatment targets,” Pepine said. “They further stated that even lower targets are in order for some subgroups of patients with coronary disease, such as those with coexisting kidney disease or peripheral artery disease. I am pleased that they believe it is important to recognize the increased risk of these other conditions. Because HF is highly prevalent among these patients with CAD and hypertension, I would have also encouraged the panel to include it among those with lower treatment targets. Finally, while we all remember that increased age, female sex, black race and prior stroke or transient ischemic attack increase risk for stroke, we often forget that the patient with prior MI is also at higher risk for stroke.”

BP control essential

The new guidance serves as an update to a 2007 AHA scientific statement on treatment of hypertension in the prevention and management of ischemic heart disease.

Proper control of BP in patients with CAD is essential for several reasons, Clive Rosendorff, MD, PhD, DScMed, FAHA, FACC, FASH, chair of the writing group for both statements, told Cardiology Today. “If the BP is too high, there is an increased myocardial oxygen demand due to the increased left ventricular output resistance. Also, the rate of atherosclerotic change in the coronary artery may be accelerated if hypertension is not treated. And of course, these patients are at risk for other negative effects associated with hypertension, such as stroke and kidney disease,” he said.

However, dropping the diastolic BP too low also can be harmful to patients with CAD, he said.

“If you decrease the BP too low, then the flow of blood in the coronary arteries and the oxygen supply to the myocardium will decline,” Rosendorff said. “In patients with CAD and the elderly, diastole is the time when the myocardium fills with blood. Caution should be observed in lowering the diastolic BP in patients with CAD or in elderly patients who presumably have more atheroma than younger patients, and the physician should be alert to signs of ischemia as the BP goes down. The diastolic BP should not really be lowered below about 60 mm Hg.”

Rationale for targets

The 2007 scientific statement recommended a BP target of less than 130/80 mm Hg for patients with hypertension and CAD.

The rationale for the change to less than 140/90 mm Hg, Rosendorff said, is that “there seems to be a general consensus that less than 140/90 mm Hg is a reasonable target. Nearly all of the guidelines that have appeared in recent years — and there have been a lot — have recommended less than 140/90 mm Hg. However, we were impressed by the literature, which stated that while lower BP targets were not harmful to the coronary circulation, they certainly did protect against stroke. So for any patient who the physician thinks is susceptible to stroke or has had a stroke or transient ischemic attack, less than 130/80 mm Hg is appropriate.”

Specifically, the 2015 statement recommends a target of less than 140/90 mm Hg in patients with CAD, ACS or HF; a target of less than 130/80 mm Hg in certain patients with CAD, including those who have had MI, stroke, TIA, carotid artery disease, PAD or abdominal aortic aneurysm; and less than 150/90 mm Hg in patients older than 80 years. However, only a target of less than 140/90 mm Hg in patients with CAD was a class I, level of evidence A recommendation.

Howard S. Weintraub, MD, FACC, clinical professor of medicine at the New York University School of Medicine and clinical director of the NYU Center for the Prevention of Cardiovascular Disease, told Cardiology Today that a major reason for the difference between the new and old scientific statements is that the previous recommendations relied more on studies based on surrogate outcomes data. “There was one study that looked at BP lowering and carotid intimal thickness data and, on the basis of that, the recommendations were made [in 2007] to lower systolic BP to less than 130 mm Hg,” he said. “While I believe 120 mm Hg to 130 mm Hg may be a better number than 130 mm Hg to 140 mm Hg, not just in special patients but in most patients, I fully understand the reason why they retreated.”

Some members of the panel noted that mean achieved BP in many of the trials showing benefit of lowering BP to less than 140/90 mm Hg was closer to 130 mm Hg/80 mm Hg, and suggested a recommendation of 130 to 140/80 mm Hg to 90 mm Hg, but the full committee did not agree because the trials did not specify a target of less than 130/80 mm Hg, panel member William B. White, MD, FASH, FAHA, FACP, professor of medicine and chief of the division of hypertension and clinical pharmacology at Calhoun Cardiology Center, University of Connecticut School of Medicine, told Cardiology Today.

“We didn’t have the evidence to absolutely support that, but we felt strongly that we had the evidence to support a target of less than 140 mm Hg/90 mm Hg for any patient with hypertension and CAD,” White said. “As far as chronic treatment, there are very few subgroups that need to be targeted to less than 130/80 mm Hg. That said, if somebody is in the range of 130/80 mm Hg and doing well clinically, we certainly would not recommend backing off drugs. If it is working and there are no clinical consequences of the drug therapy, stick with it.”

Challenges with targets

The difficulty in setting a target is that there is not much definitive clinical trial evidence supporting a particular goal, Rosendorff, professor of medicine and cardiology at Icahn School of Medicine at Mount Sinai and director of graduate medical education at the James J. Peters Veterans Administration Medical Center, Bronx, New York, said in an interview.

“There is not a lot of strong evidence for 140/90 mm Hg; in fact, there have been very few studies that have looked at the differences between target BPs in terms of outcomes,” he said.

The most prominent study of outcomes related to BP targets was ACCORD, a study of 4,733 participants with type 2 diabetes, which found no difference in the primary outcome of nonfatal MI, nonfatal stroke or CV death in those assigned to a systolic BP target of less than 120 mm Hg compared with a target of less than 140 mm Hg (HR = 0.88; 95% CI, 0.73-1.06).

Patients treated to less than 120 mm Hg had a lower rate of stroke, a prespecified secondary outcome of the study, compared with those treated to less than 140 mm Hg (HR = 0.59; 95% CI, 0.39-0.89). Rosendorff said this finding has prompted a lot of debate, with some saying that it justifies treating people at risk for stroke to a lower BP target, and others saying that the sample size was not large enough to draw any definitive conclusions.

Weintraub told Cardiology Today that the ACCORD results were enough to convince him that high-risk patients should be treated to a lower BP target, especially because the stroke results are consistent with observational studies and pathophysiological research.

“Here’s the problem: In an era where we are so strangled by the data, the idea is that if there was not a priori identification of stroke as an independent primary outcome, then the fact that the primary outcome itself did not reach significance says we are totally dismissing lowering BP,” he said. “And that’s wrong. Life does not always conform to the goals set by an investigator.”

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA, professor of clinical medicine at Tulane Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, and immediate past chair of the National Forum for Heart Disease and Stroke Prevention, agreed that patients with CAD at high risk for stroke should receive aggressive BP lowering.

“Because of the direct relationship between BP and cerebrovascular disease, and because stroke remains the leading cause of disability in the United States and is presently calculated to be the fifth leading cause of death, if we can impact stroke with lower BP goals as tolerated, it makes good sense to do so. Despite admittedly rigorous clinical trial proof, Ferdinand said, “for clinicians, tighter BP in high-risk patients for stroke is better than just suggesting, as the document written by the panel convened for the JNC 8 did, that the absence of evidence base on CV outcomes should lead us to loosen our BP goals in these high-risk patients.”

He noted that the new statement on hypertension and CAD echoes a 2014 AHA/American Stroke Association guideline for secondary prevention of stroke in those with a previous stroke or TIA. According to that document: “Although there is not strong clinical trial evidence supporting lower BPs, goal BP target should be attained to at least < 140/90 mm Hg, if tolerable, and that lower goals may be reasonable in certain patients.” Ferdinand suggested that clinicians consider that “because of the robust observational and epidemiologic data, if a patient has an active lifestyle, tolerates medications well and does not appear to have any evidence of orthostasis that the more robust, lower goals be attained.”

The SPRINT trial, which is comparing outcomes in people without diabetes assigned to a systolic BP target of less than 120 mm Hg vs. less than 140 mm Hg, could shed further light on the matter, Rosendorff said. Results are expected in 2 or 3 years.

Recommended therapies

As in the 2007 guideline, the 2015 scientific statement recommends beta-blockers as a first-line therapy for patients with hypertension and CAD. This is in contrast to guidelines on hypertension in patients without CAD, most of which recommend beta-blockers as no better than a fourth-line therapy.

“In patients who do have CAD, beta-blockers move from limbo, where they have been consigned, to center stage, and are one of the first drugs of choice,” Rosendorff said. “The reasons for this are perfectly straightforward: Beta-blockers have been shown to provide protection from another MI, and they are good for the heart. They reduce the heart rate and lower BP, both of which reduce myocardial oxygen demand. By slowing the heart, they prolong the diastolic filling pressure of the heart. If you prolong the diastolic filling period, you increase the myocardial blood flow, which increases myocardial oxygen supply.”

ACE inhibitors, angiotensin receptor blockers and diuretics also have been shown to have cardioprotective effects and are recommended for use in patients with hypertension and CAD, according to Rosendorff. “Other drugs, such as calcium channel blockers, are reasonable options for the treatment of hypertension, but the evidence for cardioprotection is not nearly as strong as with the ACE inhibitors and angiotensin receptor blockers,” he said.

For patients with hypertension and HF of ischemic origin, ACE inhibitors or angiotensin receptor blockers, beta-blockers and aldosterone receptor antagonists such as spironolactone or eplerenone are the essential components of treatment, Rosendorff said. The statement also recommends thiazides or thiazide-type diuretics if BP control and volume overload reversal are needed.

The new scientific statement has more emphasis on treatment of hypertension in patients with HF of ischemic origin because, since 2007, “more data had come out on the management of hypertension with HF,” White, past president of ASH, said. “In particular, there was a new study with eplerenone in mild-to-moderate HF that demonstrated an improvement in outcomes. We definitely believe [aldosterone blockers] are proven clinically in patients with hypertension and reduced systolic function HF and coronary disease.”

One helpful aspect of this scientific statement is delineation of drugs to avoid in this population, Pepine said. “The writing group pointed out the potential very serious problems associated with some of the drugs that you would be using in this population,” he said. For example, in patients with ACS, there is no evidence that nitroglycerin improves outcomes, there is some evidence that it can be harmful in patients with inferior STEMI, and it should not be used at the expense of agents with proven benefits on outcomes in those patients, according to the statement. Furthermore, there is no evidence that hydrazaline monotherapy is helpful and data from the ALLHAT study of doxazosin showed an association with increased stroke and HF, so these agents need to be avoided.

Research gaps remain

Despite all of the research that was incorporated into the new scientific statement, there remain quite a few areas where more investigation is required, experts said.

“The biggest gap in my mind is that we do not have enough information in much older people,” White said. “We know very little about management of elderly people with hypertension and CAD or hypertension and HF, and which drug therapies might be most satisfactory in that population. Another gap is that there is not enough information on what is the best BP to target when a patient is in the hospital having an ACS. There have been no clinical trials that suggest we should try to target one BP vs. another for the time they are in the hospital or the time of discharge from the hospital to protect them against a recurrent event.”

More research should also be conducted in patients who develop CAD despite optimal control of hypertension, lipids and lifestyle factors, Rosendorff said.

“If a lower BP is indeed better for high-risk patients, then more research must be done on the lowest pressure that we can safely achieve in this hypertensive CAD population,” Pepine said. “If we know that a lower BP will result in less stroke, less HF and probably less MI and chronic kidney disease, then maybe we should be going for a lower target in everybody. The problem is that these large trials are very costly. We will probably have to do pragmatic trials in people who are already in large electronic databases.”

Clinical judgment still necessary

With the recommendations of targets and therapies varying within the patient population, the new scientific statement has made more room for clinical judgment than most recent guidelines on prevention, experts told Cardiology Today. That is a factor that should not be phased out because not every patient will respond the same to every treatment, they said.

“Guidelines and scientific statements have to reflect the reality that for the individual patient, there is no one particular number or one particular medication that is appropriate, and clinicians have to recognize that what is appropriate for one patient may not be appropriate for another,” Ferdinand said.

Weintraub agreed, noting that some recent guidelines “divorce science” from their recommendations. “It is not unreasonable [to believe] that one size does not fit all,” he said. “If I have a 40-year-old woman who is overweight and has a family history and can’t figure out how to stop eating salt, I am not going to treat her as aggressively as a 60-year-old with a gram of protein in his urine, left ventricular hypertrophy on ECG and echocardiography, and documented coronary disease. I will approach the two very differently, not just in which medicines I am going to use, but in what my targets are going to be.” – by Erik Swain

References:

Chobanian AV, et al. Hypertension. 2003;doi:10.1161/01.HYP.0000107251.49515.c2.

James PA, et al. JAMA. 2014;doi:10.1001/jama.2013.284427.

Kernan WN, et al. Stroke. 2014;doi:10.1161/STR.0000000000000024.

Lewington S, et al. Lancet. 2002;doi:10.1016/S0140-6736(02)11911-8.

Rosendorff C, et al. Circulation. 2007;doi:10.1161/CIRCULATIONAHA.107.183885.

Rosendorff C, et al. Circulation. 2015;doi:10.1161/CIR.0000000000000207.

Rosendorff C, et al. Hypertension. 2015;doi:10.1161/HYP.0000000000000018.

The ACCORD Study Group. N Engl J Med. 2010;doi:10.1056/NEJMoa1001286.

For more information:

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA, can be reached at Tulane University School of Medicine, 1430 Tulane Ave., SL-48, New Orleans, LA 70112; email: kferdina@tulane.edu.

Carl J. Pepine, MD, MACC, can be reached at the Cardiology Today office, 6900 Grove Road, Thorofare, NJ 08086; email: carl.pepine@medicine.ufl.edu.

Clive Rosendorff, MD, PhD, DScMed, FAHA, FACC, FASH, can be reached at James J. Peters Veterans Administration Floor 7, Room A-11, 130 West Kingsbridge Road, Bronx, NY 10468; email: clive.rosendorff@va.gov.

Howard S. Weintraub, MD, FACC, can be reached 530 First Ave., Suite 4F, New York, NY 10016; email: howard.weintraub@nyumc.org.

William B. White, MD, FASH, FAHA, FACP, can be reached at University of Connecticut School of Medicine, MC 3940, 263 Farmington Ave., Farmington, CT 06030; email: wwhite@uchc.edu.

Disclosures: Ferdinand, Pepine, Rosendorff, Weintraub and White report no relevant financial disclosures pertaining to hypertension.