Recent Trends in Hypertension Management: Questions & Answers (Dr. Vasilios Papademetriou, USA)

The concept of 'lower the better' no longer holds true because recent studies that have evaluated the effect of intensive blood pressure control (110 - 120 mm Hg) have failed to show any additional benefit on cardiovascular risk reduction over standard blood pressure control (110 - 130 mm Hg). In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, intensive blood pressure control (<120 mm Hg) did not significantly reduce the combined risk of fatal or nonfatal cardiovascular events in type-2 diabetics at high risk of cardiovascular events as compared to the standard blood pressure control (<140 mm Hg).

The concept of 'earlier the better' has come from some of the studies published over the last few years. Like, in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study, attaining blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits in terms of major cardiovascular outcomes. Thus, it emphasized the importance of prompt blood pressure control in hypertensive patients.

Hence, our objective should be to bring patients to goal as early as possible to prevent vascular damage.

Diastolic blood pressure has a prognostic significance. Patients having low diastolic blood pressure should not be ignored because pulse pressure is a very strong predictor of mortality. I would check for presence of coronary heart disease in such patients.

If the diastolic blood pressure goes below 60 mm Hg, the CV risk is increased. Hence, we have to be careful on how low we go with respect to the systolic blood pressure. If the systolic blood pressure is ≥160 mm Hg and diastolic blood pressure is ≤60 mm Hg, then I would try to maintain the systolic blood pressure between 140 and 160 mm Hg.

Although there have been certain controversies in the past regarding use of beta blockers in hypertension, I do not think that beta blockers occupy secondary position in hypertension management. Beta blockers have a very important role to play in hypertension and particularly in patients with co-morbid conditions like heart failure, post MI, coronary disease and stroke. Beta blockers are very useful in patients with increased heart rate.

There are many patients with uncontrolled hypertension who have activated sympathetic nervous system. The best way to block the sympathetic nervous system and to reduce heart rate to 60-65 in these cases is with the use of beta blockers. They also give good vascular protection over the long term. In fact, a recently published meta-analysis has shown that beta blockers are also important in preventing cardiovascular complications in patients with coronary disease and post MI.

The older non-cardio-selective beta blockers, in certain patients, are likely to be associated with side effects like fatigue, lack of energy and sexual dysfunction. Newer beta blockers like nebivolol are as effective as other beta blockers and, in addition, better tolerated.

In the United States, nebivolol has been available since 2-3 years and the clinical experience with it has been good. The anti-hypertensive activity of nebivolol is at least as good as other beta blockers. Data comparing nebivolol to metoprolol suggests that once-daily dose of 10 mg nebivolol is better than twice-daily dose of 50 mg metoprolol. In low renin hypertensives, like African Americans, the 5 mg dose doesn't work well, so mostly 10 and 20 mg doses are used.

Nebivolol in combination with a thiazide diuretic results in an additive anti-hypertensive effect. In one study, the combination of 10 mg nebivolol and 25 mg hydrochlorothiazide reduced systolic blood pressure by 29 mm Hg.

Overall, I am satisfied with the anti-hypertensive activity of nebivolol as a primary drug for blood pressure reduction.

Yes, there is a need for trials comparing nebivolol with an ARB. It will give us proof of the additional benefits.

There may be small differences in terms of potency of different ARBs, which may be dose or population related. But, overall the efficacy of all ARBs is similar.

ARBs or ACE-inhibitors slow the progression of renal disease. There is no reason to discontinue ARBs in a patient with serum creatinine of 2 mg/dL unless there is volume depletion or hemodynamics is affected or serum creatinine has increased by 30-40%.

The serum creatinine cut-off point for not using ARBs or ACE-inhibitor is 3.5 mg/dL. We always consider using an ACE-inhibitor or ARB below serum creatinine 3.5 mg/dL and try to manage any further increase in creatinine. If the patient's baseline serum creatinine is 2 mg/dL and it increases to 2.8 mg/dL, and then I would temporarily discontinue ARB therapy, try to stabilize renal function and then continue the ARB therapy.

The additional blood pressure reduction with the combination of an ARB and ACE-inhibitor is small. In one of my papers published 5-6 years ago, I had reported that there was additional blood pressure reduction of only 2 mm Hg when an ACE-inhibitor was combined with an ARB. ARB and ACE-inhibitor when given as monotherapy give good vascular protective benefits but their combination has not shown any additional benefits.

If an ARB or ACE-inhibitor monotherapy is ineffective in preventing or improving proteinuria, then a combination of an ARB and ACE-inhibitor can be considered. In fact, doctors in United States, especially nephrologists, use this combination to have additional beneficial effects on proteinuria.

Occasionally, I use this combination in patients with heart failure. The CHARM-Added study demonstrated the efficacy of ARB and ACE-inhibitor combination in CHF patients who were not responding to the maximum dose of ACE-inhibitor.

The combination of an ARB and amlodipine can be used as first-line therapy in patients with stage-2 hypertension but not for all patients. Other combinations like an ACE-inhibitor or ARB with a diuretic are equally effective and can also be used as first-line therapy in patients with stage-2 hypertension.

Alpha blockers are not considered as first-line therapy in hypertension. They also increase the risk of heart failure and stroke. I would only consider using alpha blockers in hypertensives with BPH.

If these young hypertensives have tachycardia, then my preference would be a beta blocker. The acceptable heart rate is 60-70 beats/min. If the patients do not have tachycardia, then my preference would be an ACE-inhibitor or ARB.

In emergency cases, my first choice is labetalol. Clonidine can also be used. In hospitalized patients with malignant hypertension, I would prefer using sodium nitroprusside or sometimes nitroglycerine IV.

My first preference is methyldopa because it has a good safety data and my next preference would be hydralazine. Beta blockers can be used after the first trimester. I would avoid using ACE-inhibitors or ARBs in pregnant women.

I do not prescribe aspirin routinely in hypertensive patients. Aspirin should be prescribed only in patients having coronary disease or who have suffered from any vascular event.

Sleep apnea is a passive cause of uncontrolled hypertension and is commonly seen in obese patients. If a patient's blood pressure is controlled with 1 or 2 medicines, then he is unlikely to have sleep apnea. We should look for presence of sleep apnea in any patient whose blood pressure is difficult to control.

In such patients, I do not stop at three medicines. As per the tolerance of the patient, I would try to add as many medications as possible. Patients implanted with mechanical devices for blood pressure control were, on an average, receiving 6 drugs. If we have a patient with uncontrolled hypertension despite taking an ACE-inhibitor, a diuretic, beta blocker and a calcium channel blocker, then I would try to add clonidine and then minoxidil or even consider adding a second calcium channel blocker. Occasionally, I would try reserpine in some patients.

Using mechanical devices in moderate hypertensives and non-compliant patients is a good possibility. Actually, I expect a better response in these patients because they have healthier baroreceptors and depend a lot more on their renal innervations. But, due to ethical reasons, the FDA does not allow studies of invasive mechanical devices in patients who can be controlled by oral medication. With time, if the safety of these devices in validated, then maybe we can have data in milder hypertensives and I expect that we will see a lot of benefit in these patients.

Renal artery stenosis should be considered in cases of resistant hypertension, but stenting it is not going to provide a solution. Rarely has stenting of renal artery resulted in BP normalization.

We look for the presence of renal artery stenosis in patients who develop flash pulmonary edema. If renal artery stenosis is present in such cases, then we stent it. Even if we find a patient who has a very high blood pressure and arterial stenosis, we would rarely stent them unless we find presence of very tight lesions or very symptomatic flash pulmonary edema.

Stenting of renal artery stenosis may help to improve renal function in very few patients, but, it does not make a difference in the majority of patients.