Marvin Moser

Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials.

OBJECTIVES This work was done to determine the role of hypertension treatment in the prevention of disease progression, left ventricular hypertrophy and congestive heart failure. BACKGROUND Lowering of blood pressure in hypertensive patients has been reported to reduce morbidity and mortality from strokes and myocardial infarction. Data on primary prevention of disease progression, left ventricular hypertrophy and congestive heart failure have not previously been carefully quantified. METHODS All the major long-term hypertension treatment trials over the past 20 years were reviewed. RESULTS One thousand four hundred ninety-three of 13,342 subjects in the control groups compared with only 95 of 13,389 in the treated groups progressed from less severe to severe hypertension. The incidence of left ventricular hypertrophy in treated compared with control or placebo subjects was 140 of 6,150 and 216 of 6,098 subjects, respectively; congestive heart failure occurred in 240 of 6,923 subjects in the control group compared with only 112 of 6,914 treated subjects. CONCLUSIONS The lowering of blood pressure over a 3- to 5-year period of time is effective in preventing severe disease, left ventricular hypertrophy and congestive heart failure in addition to strokes and myocardial infarction. In an era when expensive and often complicated methods are being used to prevent recurrence of congestive heart failure or myocardial infarction, it is important to highlight the role of antihypertensive therapy in primary prevention.

Use of Diuretics in Patients with Hypertension

This review focuses on thiazides, the diuretics most often indicated for long-term therapy for hypertension. Thiazide diuretics reduce blood pressure when administered as monotherapy; thiazides also enhance the efficacy of other antihypertensive agents and can reduce hypertension-related morbidity and mortality.

Treatment of hypertension in the very elderly: a clinician's point of view.

Dihydropyridine calcium channel blockers comprise a class of powerful, well-tolerated, and safe antihypertensive agents that are widely used either alone or as a key component of combination therapy for hypertension. Peripheral edema, particularly of the lower limbs, is one of the most common adverse effects of dihydropyridine calcium channel blockers and may result in the need for dose reduction or drug withdrawal, both of which can adversely affect antihypertensive efficacy. Optimal use of these important drugs will involve careful dosing and sensitivity to strategies to diminish the likelihood of edema. Diuretics, either loop or thiazide, are usually not effective in alleviating pedal edema. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in combination with a dihydropyridine calcium channel blocker may be helpful in this regard. Some calcium channel blockers may be less likely to cause pedal edema compared with others. This paper will review existing explanations of why there may be differences. A favorable tolerability profile is of particular importance for an antihypertensive medication, since hypertension is a chronic disorder necessitating long-term treatment and patient compliance.

Responses to captopril and hydrochlorothiazide in black patients with hypertension

The effects of Captopril (C) in doses of up to 450 mg/day, placebo (P), and hydrochlorothiazide (H) in doses of 50 to 100 mg/day were compared in double‐blind studies in 38 black patients. Mean blood pressure response to C was only slightly greater than to P (systolic response difference only). Mean blood pressure responses to H were greater than to C. Results were compared to available data on 185 white and black patients treated similarly. In white patients, response to C was greater than to P, but response to H was approximately equal to that to C. In black patients, results were of the same order as those reported here; the systolic response to C was greater than that to P and the response to H was greater than that to C. These data suggest that black and white patients differ in response to certain antihypertensive drugs.

The role of combination therapy in the treatment of hypertension.

Only approximately 40% to 50% of hypertensive patients will achieve goal blood pressures of <140/ 90 mm Hg with monotherapy, regardless of the medication used. Fixed-dose combination therapy with two different classes of antihypertensive agents will achieve goal pressures in more than 70%. The sixth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has suggested that the use of combination therapy is appropriate as initial treatment. The advantages of combinations include: 1) greater blood pressure decrease and response rates than monotherapy; 2) fewer side effects with small doses of two drugs than with large doses of one agent; 3) improved adherence to treatment; and 4) possibly lower cost of therapy. Many different combinations of diuretics and beta-blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, as well as ACE inhibitors and calcium antagonists are available. Two of these, Ziac and Capozide, have been approved as initial therapy. It is possible that the number of hypertensive individuals controlled at goal blood pressure levels will be increased if combination therapy is used as initial treatment.

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension.

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists and Calcium Channel Blocking Agents: A Review of Potential Benefits and Possible Adverse Reactions

A review of recent studies suggests that the use of angiotensin-converting enzyme (ACE) inhibitors may be preferred (usually along with a diuretic drug) as initial therapy in several subsets of hypertensive patients (i.e., those with diabetes and nephropathy or with diminished left ventricular function with or without symptoms of heart failure). Limited long-term data are available for the angiotensin II receptor antagonists. The use of nondihydropyridine calcium channel blocking agents (CCBs) appears to reduce reinfarction in patients with ischemic heart disease (however, mortality is not reduced). Long-acting formulas of CCBs appear to decrease congestive heart failure in patients with dilated, but not ischemic, cardiomyopathy and to decrease strokes and arrhythmias in hypertensive subjects. Short-acting agents (primarily those that increase heart rate) may increase coronary heart disease events in hypertensive patients. There is little evidence at present that CCBs offer a major advantage over other antihypertensive agents or that they should be recommended as initial therapy, except in special situations.

Long-Term Effects of Furosemide and Hydrochlorothiazide in Patients With Essential Hypertension A Two-Year Comparison of Efficacy and Safety

In a double-blind study the long-term effects of diuretics in uncompli cated mild and moderate essential hypertension were investigated. A total of 52 outpatients completed 24 months of treatment with either furose mide at a dose of 40 mg twice daily (26 patients) or hydrochlorothiazide at a dose of 50 mg twice daily (26 patients). Throughout the 2 years of the study, both furosemide and hydro chlorothiazide significantly lowered the mean supine blood pressure from baseline levels. The fall was less with furosemide than with hydrochloro thiazide, although the difference between the two drugs reached statistical significance at only three of the eight time points. Serum electrolytes were used as major indicators of safety. The cumulative incidence of hypokalemia of 8% for the furosemide group compared to that of 62% for the hydrochlorothiazide group. Although diuretics, alone or combined with other blood pressure-lower ing drugs, have been used for many years to treat essential hypertension, information on their continued efficacy and safety is scarce. Short-term trials had shown that furosemide (Lasix(®)) resembled the thiazides in its antihypertensive properties,1-3 despite its different mode of action on the kidney. A cooperative study in hypertensive patients was therefore under taken at three clinical centers to investigate the long-term effects of furose mide on blood pressure and on serum electrolytes, and to compare them with those of hydrochlorothiazide.

Pheochromocytoma and the abnormal electrocardiogram

Abstract 1. 1. Two patients with pheochromocytoma and abnormal electrocardiograms due to the presence of this tumor are reported. Serial tracings illustrating the effects of surgery, as well as the administration of adrenolytic agents, are presented. 2. 2. Pertinent literature is reviewed, and it is observed that the association of pheochromocytoma and electrocardiographic abnormalities has been previously noted though recently neglected. 3. 3. The reported abnormalities are either arrhythmias or changes suggesting myocardial damage, ischemia, or “strain.” A singularly striking feature of the latter group is the diffuse distribution of the S-T segment and T-wave changes. 4. 4. The role of excessive circulating epinephrine and/or norepinephrine in the production of these changes is discussed. 5. 5. It is emphasized that in the absence of known etiology certain electrocardiographic abnormalities may indicate the presence of a pheochromocytoma.

Antihypertensive medications: relative effectiveness and adverse reactions.

Thiazide diuretics may be more effective as antihypertensive agents in many subsets of patients than other medications, especially in reducing systolic blood pressure. Angiotensin converting enzyme (ACE) inhibitors and p-blockers are less effective than calcium blockers or diuretics in black hypertensives and p-blockers may be less effective in the elderly. Calcium blockers are equally effective in blacks, whites and the elderly but may not be as efficacious as diuretics. When used as initial monotherapy, most available antihypertensive drugs produce significant adverse subjective effects in about 8—:% of patients; centrally acting drugs, however, may produce annoying side effects in 20-30% of patients. Usually, some medication can be found that lowers blood pressure and is acceptable to the patient. Adverse metabolic effects are probably of limited long-term clinical significance except in a few patients. An approach to therapy that will prove effective in a majority of patients is outlined. Any one of the four classes of agents may appropriately be used as initial monotherapy (diuretics, p-blockers, ACE inhibitors, calcium blockers). Diuretics are recommended as the second drug of choice if one of the other agents is used first. With this approach approximately 80% or more of patients can be controlled at normotensive levels on one or at most two drugs