Drug therapy or lifestyle modification

The lifestyle modifications recommended by the JNC 7 were mostly nutritional, consisting of weight loss in the overweight, lowering of dietary sodium intake to less than 100 mmol day, modification of alcohol intake to, at most, two drinks per day, and maintenance of an adequate dietary intake of potassium, calcium, and magnesium 2 . The JNC 7 also recommended regular physical activity for all patients with hypertension who have no conditions that would make exercise contraindicated. There is...

Antihypertensive therapy in physically active patients

Lifestyle modifications often have to be adapted to fit a specific antihypertensive therapy and vice versa. Regular aerobic exercise has a mild antihypertensive effect, probably because oflow-grade, chronic fluid volume and salt depletion. Thus, aerobic exercise should be encouraged in all patients with hypertension conversely, drugs that decrease aerobic exercise performance, such as beta-blockers and, to a lesser extent, diuretics, should be avoided in the physically DRUG THERAPY OR LIFESTYLE...

Blood pressure lowering in prehypertensive patients

The JNC created a new BP class in 2003 called prehypertension 2 . The issue surrounding this entity has stirred tempers to an extent that seems more suitable to medieval theologians than to modern scientists. The extensively quoted meta-analysis of Lewington 33 suggested a continuous relationship between the risk of cardiovascular disease (stroke, coronary heart disease, and vascular disease) and usual BP values down to at least 115 75 mmHg. In the Framingham cohort 1 , an increase in...

Whitecoat hypertension and masked hypertension

BP is a very labile hemodynamic parameter it varies from heartbeat to heartbeat, from morning to evening, from winter to summer, from sleeping to awake, and from sitting to standing. The same holds true for any other cardiovascular hemodynamic parameter, such as heart rate, cardiac output, ejection fraction, or pulmonary wedge pressure. However, the information that is based on invasively obtained measurements is often considered more reliable than information based on simple BP recording....

Resistant hypertension

Resistant hypertension is said to be present if, despite triple therapy including a thiazide diuretic, BP remains distinctly above target range. Figure 31 lists some of the more common underlying causes of resistant hypertension. Of particular concern are NSAIDs, as well as the cyclooxygenase 2 (COX2) inhibitors. These drugs elevate BP by a variety of mechanisms, ranging from direct binding with mineralocorticoid receptors to interference with prostaglandin synthetase. Some mechanisms of...

Adverse effects and tolerability

Most antihypertensive drugs have some adverse effects that can affect tolerability. For instance, the main adverse effect of dihydropyridine calcium antagonists is pedal edema 23 , which is dose dependent and more common in women than in men. In an overweight, middle-aged woman, calcium antagonist monotherapy will almost invariably trigger, or aggravate, pedal edema and make the patient unhappy with the selection of the initial antihypertensive drug. Of note, not all dihydropyridine calcium...

When initial therapy is insufficient To uptitrate to substitute or to combine

One of the most common questions practicing physicians face after starting a patient on treatment with a given antihypertensive drug is how to proceed when BP remains elevated. That physicians are uneasy with this question is illustrated by the fact that patients are often treated for years with the same dose of the same drug or combination, despite the fact that BP is not at goal. Any excuses volunteered by the patient (ie, crowded parking garage, mother-in-law visiting) seem good enough to...

How aggressively should blood pressure be lowered

The VALUE study clearly established that patients whose BP was under control after 6 months had a much lower risk of heart attack and stroke than did patients whose BP remained elevated 32 . This appears to indicate that swift BP control should be achieved and argues against the old dictum of start low, go slow. It should be considered, however, that in the VALUE study most patients were taken off multiple drugs and were put on monotherapy (ie, valsartan 80 mg) for several months. Clearly, this...

Blood pressure lowering in normotensive patients

The Framingham study has clearly documented that, even within the normo-tensive range, patients with higher BPs have a higher risk of cardiovascular morbidity than those who have an optimal BP 1 . This raises the question of whether one should consider antihypertensive therapy in normotensive patients. Indeed, several studies have shown that lowering BP in the so-called normotensive population reduces cardiovascular morbidity and mortality. This is particularly true for stroke but less so for...

Evidencebased versus eminencebased therapy

Eminence-based therapy can be defined as making the same mistakes with increasing confidence over an impressive number of years 36 . Numerous prospective, randomized large trials have taught us what is now defined as evidence-based medicine (EBM) in the treatment of hypertension. However, a critical analysis of these trials remains extremely important because they provide the results that should be translated into clinical practice. For instance, the SHEP program 18 is commonly used as EBM for...

Diuretics and diuretic combinations

Fixed combinations of a thiazide diuretic and a potassium-sparing drug are commonly used as initial therapy for the treatment of hypertension. In the USA, there are three such fixed combinations available (Figure 11). Of note, triamterene and amiloride have relatively little diuretic or antihypertensive effect, whereas spironolactone and eplerenone act synergistically on BP. Amiloride 5 or 2.5 mg HCTZ 50 mg Spironolactone 25 or 50 mg HCTZ 50 or 25 mg Triamterene 37.5, 50, or 75 mg HCTZ 25 or 50...

Antiadrenergic and diuretic combinations

Diuretic and antiadrenergic combinations were common a few years ago, but are sparingly used in this day and age. Most contain fairly high doses of diuretics and some have to be given twice a day (Figure 13). Antiadrenergic drugs, such as methyldopa, clonidine, guanabenz, and even reserpine, have a favorable effect on a variety of pathophysiologic findings of hypertensive cardiovascular disease. These drugs reduce LVH, vascular hypertrophy, vascular resistance, and proteinuria, maintain cardiac...

Calcium antagonist and diuretic combinations

The general clinical contention that a diuretic should not be combined with a calcium antagonist, unless there is edema caused by calcium antagonist monotherapy, is wrong for several reasons. In the early 1980s, an uncontrolled study in a small number of patients showed that the addition of a diuretic to verapamil had no additive effect on BP. Ever since this study, physicians have been reluctant to combine a diuretic with a calcium antagonist, dihydropyridine or not. However, several large,...

Calcium antagonist and betablocker combinations

In the USA, no fixed combination of a calcium antagonist with a beta-blocker is available. However, in Europe, at least one such combination is on the market and has been quite successful. Short-acting calcium antagonists are well known to produce cardio-acceleration, an increase in heart rate and cardiac output, and sympathetic stimulation. With the long-acting, once-a-day agents, cardio-acceleration and sympathetic stimulation are minimal but can still be documented with some dihydropyridine...

Betablockers with either ACE inhibitors or ARBs

No fixed combination is available of a beta-blocker with either an ACE inhibitor or an ARB, indicating that there is little interest in developing such a combination. Indeed, there are some reasons to suspect that such a combination may have a distinctly less-than-additive effect on BP this viewpoint is supported by the ALLHAT study 43 . Although beta-blockers have been available for the treatment of hypertension for a number of decades, the mechanism of their antihypertensive effect is still...

Direct renin inhibitor and diuretic combinations

What has been said for ACE inhibitors and ARBs in combination with thiazide diuretics holds true as well as direct renin inhibitors. The only one presently available is aliskiren and it comes in a fixed-dose combination with hydrochlorothiazide. Similar to other RAS blockers, presence ofhydrochloro-thiazide increases the activity of the renin-angiotensin system and makes the blood pressure more amenable to the effects of direct renin inhibitor. Schmieder et al. showed that aliskiren treatment...

Synergism of combination therapy

The most common adverse effect of the dihydropyridine calcium antagonist is pedal edema, which is clearly dose dependent. Pedal edema is seen in about 5 of patients on amlodipine 5 mg, in 25 of patients on amlodipine 10 mg, and in over 80 of patients on amlodipine 20 mg (which is above the FDA-approved dose). Pedal edema is predominantly caused by arteriolar dilatation that increases intracapillary pressure (capillary hypertension) and thereby causes fluid exudation into the interstitium...

When not to use fixed combination therapy

As attractive as fixed combinations are, and although many patients benefit from them, it should be remembered that not every patient with mild to moderately severe hypertension is a candidate for such therapy. Patients need to be thoroughly informed that they are taking a combination of drugs, such as an ARB and a diuretic, in the same pill. Commonly, the labeling of fixed combinations may be deceptive to patients and physicians. In numerous instances, patients have been given inappropriate...

The prothrombotic paradox

Hypertension by definition is a hemodynamic disorder and, as such, exposes the arterial tree to increased pulsatile stress. Paradoxically, however, most major complications of longstanding hypertension (ie, heart attack and strokes) are thrombotic rather than hemorrhagic, referred to as the so-called thrombotic paradox of hypertension. Virchow suggested three components facilitating thrombus formation (Virchow's triad) For thromboembolic events to take place, all the components of Virchow's...

The I want to do it the natural way patient

Not uncommonly, the physician is challenged by a patient who insists on doing it his or her own natural way. Even though most physicians recognize that this endeavor will be futile, an enthusiastic patient should be encouraged to exercise regularly, lose weight and follow a healthy sodium-restricted diet. The only harm that can come from this is that BP remains elevated and the cardiovascular system of the patient continues to be exposed to a high pressure load. It is therefore important to...

Dual calcium channel blockade

Occasionally, the combination of a dihydropyridine and a nondihydropy-ridine calcium antagonist may be considered. There is some evidence of an additive effect of this combination and it seems, in general, to be well tolerated 102 . Pedal edema is not aggravated by the addition of a nondihydro-pyridine calcium antagonist to a dihydropyridine agent. The combination may be particularly useful in patients with renal failure and hyperkalemia in whom RAS blockade has become relatively...

The J curve

Much ink has been expended on whether the relationship between BP and cardiovascular morbidity and mortality follows a J-shaped pattern. Conceivably, as BP is lowered, morbidity and mortality diminish, but, clearly, there is a point at which further lowering leads to the under-perfusion of vital organs and, thereby, will increase morbidity and mortality. Thus, it stands to reason that a J curve has to exist. However, it is not so clear whether the nadir of the J curve is anywhere near the...

Lowsalt diet

Lifestyle modifications can profoundly affect antihypertensive therapy for instance, a low sodium diet will decrease potassium excretion in a patient who is on a diuretic, as less sodium is available at the level of the distal tubule for exchange against potassium. Thus, a low-sodium diet will prevent total body potassium depletion and, thereby, may enhance the morbidity and mortality benefits of diuretic therapy. In the Systolic Hypertension in the Elderly (SHEP) study 12 , patients who had...

Outcome

The drug class best documented to reduce morbidity and mortality in hypertension, when compared with either placebo or active therapy, remains the thiazide diuretics, specifically chlorthalidone. In all diuretic-based trials, other antihypertensive drug classes, such as beta-blockers and antiadrenergics, have been added to titrate BP to target. However, although the addition of these drugs to diuretic therapy adds to the antihypertensive efficacy (and therefore, seemingly has a beneficial...

Substitution

Substituting a different antihypertensive drug should be considered if there is no antihypertensive efficacy with a reasonable dose, as is occasionally seen with beta-blockers, ACE inhibitors or ARBs in black patients, or if there are intolerable side effects, such as angioedema. Fortunately, most modern antihypertensive drugs are well tolerated and serious adverse effects are few. Some patients are even willing to put up with a scratchy throat or low-grade cough associated with ACE inhibitors,...

Drug interactions

Drug-drug interactions have become increasingly important over the past few decades because, in most cases, two or more drugs are needed to get BP to goal, and also because hypertension is rarely an isolated disorder and concomitant risk factors or diseases may require multiple drugs that can, potentially, interact with a given antihypertensive agent. It is almost impossible for the practicing physician to remember all potential interactions, some of which can lead to severe and even fatal...

Atrial fibrillation

Atrial fibrillation is an under-recognized complication of long-standing hypertension and increases the likelihood of morbidity and mortality - at least doubling the risk for cardiovascular death or stroke. The main factors predicting development of atrial fibrillation are age, male sex, severity of hypertension, obesity, and presence of LVH on electrocardiogram. Some findings suggest that the choice of BP-lowering treatment could reduce the risk of developing atrial fibrillation. Notably,...

Hyperlipidemia

Diuretics and traditional beta-blockers, such as atenolol and metoprolol, are known to increase triglycerides and to lower high-density lipoprotein cholesterol levels (Figure 28). In contrast, vasodilating beta-blockers, such as carvedilol, and ACE inhibitors, calcium antagonists, and alpha-blockers are metabolically neutral, or may even have a slightly favorable effect on lipoproteins. The effects of antihypertensive agents on lipids (rarely given alone effects not known) Figure 28 The effects...

Dementia

Dementia is a major concern in the elderly hypertensive patient. Patients with hypertension have been shown to suffer cognitive dysfunction and dementia of all types more commonly than do normotensive subjects. The effects of antihypertensive therapy on dementia are not well documented. However, provocative findings from the Syst-Eur trial have shown that dihydropyridine calcium antagonists reduce dementia by as much as 55 (Figure 29) 69 . In some, but not all, studies, statins also showed a...

Nephroprotection

In the patient with diabetic hypertensive renal disease, blockade of the RAS has been shown to be nephroprotective that is, to diminish proteinuria and slow down the decline in renal function. In type 1 diabetes, most proteinuria studies have used ACE inhibitors, whereas, for type 2 diabetes, ARBs have mostly been used. However, the American Diabetes Association (ADA) have concluded that the evidence was sufficient to state that both drug classes, ACE inhibitors and ARBs, are indicated for...

Black patients

Hypertension is more common in black than in white patients, and its course is distinctly more severe. Black patients have a three-times higher mortality rate from cardiovascular disease than do white patients, and their risk of end-stage renal disease is several times greater. These simple facts indicate that cardiovascular diseases, such as hypertension, hyperlipidemia, and diabetes, should be treated most aggressively in the black population. However, the impediments to aggressive therapy in...

Alcohol abuse

The pathogenesis of BP elevation in patients who abuse alcohol is multi-factorial. Acutely, alcohol is a vasodilator but, chronically, it has a direct vasculotoxic effect and produces constriction of vascular smooth muscle. It stimulates the sympathetic nervous system, as well as the RAS, and may cause thirst and dehydration, which often are counteracted by excessive salt and water retention. Chronic alcohol abuse is not an uncommon cause of seemingly refractory hypertension. Calcium...

Uptitration

Uptitration of the original drug to double the dosage is reasonable only if distinctly enhanced antihypertensive efficacy has been documented and the cost is not prohibitive. Most antihypertensive drugs have a rather shallow dose-response curve and increasing the dose has little additional effect on BP. For instance, doubling the starting dose oflosartan from 50 mg to 100 mg, has not been shown to increase antihypertensive efficacy. In a situation like this, it is more rational to combine a low...

The nothing worksallergic to everything patient

These patients are also called heart sink patients because the physician's heart sinks whenever they show up in the waiting room. What, perhaps, is most important with patients like this is to try to sort the wheat from the chaff. Thus, a very thorough, detailed history regarding previous medications, duration of use and reasons for discontinuation can often provide an astonishing insight. If a patient who is allergic to everything lists among these allergies a dry cough with certain drugs, or...

Clinicians Manual Treatment of Hypertension

Director, Hypertension Program St Luke's-Roosevelt Hospital Center 1000 Tenth Avenue New York, NY Published by Springer Healthcare Ltd, 236 Gray's Inn Road, London, WC1X 8HB, UK www.springerhealthcare.com 2011 Springer Healthcare, a part of Springer Science+Business Media All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written...

To twofer or not to twofer

The two-for-one therapeutic concept or, namely, to treat two conditions with one drug, is attractive for a variety of reasons among these are a reduction in adverse effects, the number of pills, and cost. Physicians and patients, therefore, like the twofer and use it whenever possible. Unfortunately, the concept of the twofer has never been vigorously tested. Ironclad trials have shown that beta-blockers confer secondary cardioprotection in patients who have suffered an acute MI 26 . However,...

Hypertension as a gateway to cardiovascular risk modification

Measurement of BP is a simple, straightforward procedure that allows us to identify the risk of cardiovascular disease. However, treatment of raised BP is clearly inefficient to reduce the overall associated cardiovascular disease risk. Antihypertensive therapy should, therefore, serve as a gateway to overall cardiovascular risk management and give rise to normal risk estimation. This can be done by using the Framingham risk score 1 or the systems put forward by the European Society of...

Erectile and orgasmic dysfunction

Long-standing, untreated hypertension is well known to have a negative impact on sexual function and can lead to complete impotence. Unfortunately, antihypertensive drugs still have a bad reputation with regard to erectile function. Some of the older antihypertensive drugs, such as resurpine and guanethidine, have a well-known negative effect on erectile and orgasmic function. Diuretics, beta-blockers, and antiadrenergic drugs, as well as alpha-blockers, diminish erectile function. Failure to...

Pill burden and compliance

Experienced clinicians have long recognized that the patient's compliance with a given treatment regimen depends, to some extent, on its complexity. As a simple rule, the more pills a patient has to take the sicker he or she feels and the lesser the compliance. This is particularly true when the treatment regimen requires dosing several times a day. Fixed combinations, therefore, have a distinct advantage. Putting two or three drugs into the same pill may reduce side effects thus, the patient...

Betablocker and diuretic combinations

Several beta-blocker and diuretic combinations were marketed a number of decades ago when beta-blockers became available in the USA (Figure 12). In most of these fixed combinations, the beta-blocker is combined with 25 mg, or even 50 mg, of HCTZ (or the corresponding dose of a thiazide derivative), a dose that, by today's standard, would have to be considered high. It has been learned that HCTZ doses of 12.5 mg, and even 6.25 mg, lower BP and cause fewer endocrine metabolic adverse effects than...

Stepdown therapy

Should the patient be successful in modifying their lifestyle weeks or months after BP is controlled with antihypertensive therapy, it is reasonable to consider using the step-down approach to decrease the dose, or number, of antihypertensive drugs taken, or even to stop therapy completely. Lowering BP over the long term by using antihypertensive drugs such as ACE inhibitors, ARBs and calcium antagonists, will reduce vascular hypertrophy and target organ disease and will restore endothelial...

Antihypertensive efficacy

Concomitant medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), or a high salt intake can mitigate the antihypertensive efficacy of certain drug classes, such as ACE inhibitors or ARBs. Beta-blockers have little, if any, effect in isolated systolic hypertension in elderly patients. A high salt intake can counteract the effects of diuretics and blockers of the RAS. In contrast, few, if any, drugs or dietary interventions affect the efficacy of calcium antagonists. Calcium...

Early morning hypertension

Ever since the pioneering studies of Sir George Pickering, we have known that BP follows a distinct diurnal pattern, decreasing throughout the evening to a nadir at midnight, followed by an early morning rise shortly before awakening. This pattern is qualitatively similar in both normotensive and hypertensive patients. Hypertensive complications, such as stroke, acute MI, and sudden death follow a very similar pattern the time period between 6 00 a.m. and 10 00 a.m. seems to confer the highest...

Isolated systolic hypertension

There are three main reasons why isolated systolic hypertension has become increasingly important over the past few years We are seeing more and more elderly patients, and isolated systolic hypertension is the most common form of high BP in the geriatric population. Systolic BP has finally been recognized as the most powerful predictor of cardiovascular morbidity and mortality and, therefore, treatment of systolic BP has become more important than that of diastolic BP. The treatment goals of...

Dual RAS blockade Blood pressure

Most BP studies showed a small additional drop in systolic and diastolic pressure when an ARB was added to an ACE inhibitor, and vice versa, regardless of the dose level of the first drug. A thorough systematic review and metaanalysis assessed 14 BP studies in hypertensive patients in which patients were evaluated by 24-hour ambulatory BP monitoring 91 . The authors found that the combination of an ACE inhibitor and an ARB reduced BP by an average of 4 3 mmHg when compared with monotherapy. The...

Combination therapy

Cardiovascular risk factors, such as hypertension, diabetes, and hyperlipidemia, as well as cardiovascular disease states, such as coronary heart disease, heart failure, and certain arrhythmias, are amenable to a variety of therapeutic interventions that have been proven to be beneficial. However, the combination ofthese interventions has rarely been studied in a rigorous scientific way. No data are available that analyze the relevant contribution of each drug to the overall outcome in a given...

Outcome trials

The ASCOT study further attests to the benefit ofthe combination of an ACE inhibitor with a dihydropyridine calcium antagonist 54 . ASCOT was designed to compare the effect of the standard antihypertensive regimen (a beta-blocker and a diuretic) with that of a more contemporary regimen (calcium antagonist and an ACE inhibitor) on coronary artery disease. A total of almost 20,000 patients were randomized to either atenolol plus bendroflumethiazide (if needed) or amlodipine plus perindopril (if...