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Hydrochlorothiazide Is Not Additive to Verapamil in Treating Essential Hypertension

Hydrochlorothiazide Is Not Additive to Verapamil in Treating Essential Hypertension Abstract • Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170±17/109±6 mm Hg pretreatment to 150±25/95±8 mm Hg with verapamil; 170±5/109±2 mm Hg pretreatment to 164±25/103±10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150±25/95±8 mm Hg vs 150±20/95±6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2±0.25 mmol/L to 3.7±0.35 mmol/L) and stimulated plasma renin activity (1.5±1.3 ng/mL/h pretreatment to 3.3 ±2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 ± 1.3 ng/mL/h pretreatment to 2.7 ±2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted. (Arch Intern Med 1989;149:125-128) References 1. Whitworth JA, Kincaid-Smith P: Diuretics or beta-blockers first for hypertension? Drugs 1982;23:394-402.Crossref 2. Vaughan ED Jr, Laragh JH, Gavras I, et al: Volume factors in low and medium renin essential hypertension: Treatment with either spironolactone or chlorthalidone . Am J Cardiol 1973;32:523-532.Crossref 3. Multiple Risk Factor Intervention Trial Research Group: Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial . Am J Cardiol 1985;55:1-15.Crossref 4. Müller FB, Bolli P, Erne P, et al: Calcium antagonism: A new concept for treating essential hypertension . Am J Cardiol 1986;57:500-530.Crossref 5. Bühler F: Factors influencing the hypotensive effects of calcium antagonists . Hypertension 1983;2:97-102. 6. Resnick LM, Nicholson JP, Laragh JH: Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine . Hypertension 1987; 10:254-258.Crossref 7. DeLeeuw PW, Binkerhager SW: Effects of verapamil in hypertensive patients . Acta Med Scand 1984;681:125S-128S. 8. Kuller LH, Hulley SB, Cohen JD, et al: Unexpected effects of treating hypertensive men with electrocardiographic abnormalities: A critical analysis . Circulation 1986;73:114-123.Crossref 9. Kriker DM, Rowland E: Clinical value of calcium antagonists in treatment of cardiovascular disorders . J Am Coll Cardiol 1983;1:355-364.Crossref 10. Preibisz JJ, Sealey JE, Acteo RM, et al: Plasma renin activity measurements: An update . Cardiovasc Rev Rep 1982;3:782-787. 11. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: The 1984 report of the Joint National Committee on detection evaluation and treatment of high blood pressure . Arch Intern Med 1984;144:1045-1057.Crossref 12. Cloher TP, Wheaton PK: Physician approach to the recognition and initial management of hypertension . Arch Intern Med 1986;146:529-533.Crossref 13. Laragh JH: Modification of stepped-care approach to anti-hypertensive therapy . Am J Med 1972;77:78-86. 14. Nicholson JP, Resnick LM, Laragh JH: The antihypertensive effect of verapamil at extremes of dietary sodium intake . Ann Intern Med 1987; 107:329-334.Crossref 15. Hallin L, Anorzin L, Hansson L: Controlled trial of nifedipine and bendroflumethiazide in hypertension . J Cardiovasc Pharmacol 1983;5: 1083-1085.Crossref 16. MacGregor GA, Markandu ND, Smith SJ, et al: Does nifedipine reveal a functional abnormality of arteriolar smooth muscle cell in essential hypertension? The effect of altering sodium balance . J Cardiovasc Pharmacol 1985;7( (suppl 6) );S178-S181.Crossref 17. Benjamin N, Phillips RJW, Robinson BF: Bendrofluazide does not produce any additional fall in blood pressure in hypertensive patients taking verapamil, p 35. Program and abstracts of the Third European Meeting on Hypertension, Basel, Switzerland, February 1988. 18. Leonetti G, Frescio M, Sampiteri L, et al: Does the addition of a diuretic enhance the antihypertensive effect of the calcium antagonist tiapamil? Program and abstracts of the Third European Meeting on Hypertension, Basel, Switzerland, February 1988, p 306. 19. Frishman WH, Zawada ET, Smith LK, et al: Multicenter Comparison of Sustained Release Diltiazem for Mild to Moderate Systemic Hypertension . New York, American Society of Hypertension, 1987, pp 148-272(A). 20. Massie B, McCarthy P, Ramananathan KB, et al: Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide . Ann Intern Med 1987;107:150-157.Crossref 21. Laragh JH, Sealey JE, Niarchos AP, et al: The vasoconstriction-volume spectrum in normotension and in the pathogenesis of hypertension . Fed Proc 1982;41:2415-2483. 22. Hollifield JW, Slaton PE: Thiazide diuretics, hypokalemia and cardiac arrhythmia . Acta Med Scand 1981;647( (suppl) ):67-73. 23. Kiowski W, Bertel O, Erne P, et al: Hemodynamic and reflex mechanisms of acute and chronic antihypertensive therapy with the calcium channel blocker nifedipine . Hypertension 1983;5( (suppl 1) ):170-174.Crossref 24. Hiramatsu K, Yamagishi F, Kubota T, et al: Acute effects of the calcium antagonist, nifedipine, on blood pressure, pulse rate, and the reninangiotension-angiotensin system in patients with essential hypertension . Am Heart J 1982;104:1346-1350.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Hydrochlorothiazide Is Not Additive to Verapamil in Treating Essential Hypertension

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Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1989.00390010119015
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Abstract

Abstract • Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170±17/109±6 mm Hg pretreatment to 150±25/95±8 mm Hg with verapamil; 170±5/109±2 mm Hg pretreatment to 164±25/103±10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150±25/95±8 mm Hg vs 150±20/95±6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2±0.25 mmol/L to 3.7±0.35 mmol/L) and stimulated plasma renin activity (1.5±1.3 ng/mL/h pretreatment to 3.3 ±2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 ± 1.3 ng/mL/h pretreatment to 2.7 ±2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted. (Arch Intern Med 1989;149:125-128) References 1. Whitworth JA, Kincaid-Smith P: Diuretics or beta-blockers first for hypertension? Drugs 1982;23:394-402.Crossref 2. Vaughan ED Jr, Laragh JH, Gavras I, et al: Volume factors in low and medium renin essential hypertension: Treatment with either spironolactone or chlorthalidone . Am J Cardiol 1973;32:523-532.Crossref 3. Multiple Risk Factor Intervention Trial Research Group: Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial . Am J Cardiol 1985;55:1-15.Crossref 4. Müller FB, Bolli P, Erne P, et al: Calcium antagonism: A new concept for treating essential hypertension . Am J Cardiol 1986;57:500-530.Crossref 5. Bühler F: Factors influencing the hypotensive effects of calcium antagonists . Hypertension 1983;2:97-102. 6. Resnick LM, Nicholson JP, Laragh JH: Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine . Hypertension 1987; 10:254-258.Crossref 7. DeLeeuw PW, Binkerhager SW: Effects of verapamil in hypertensive patients . Acta Med Scand 1984;681:125S-128S. 8. Kuller LH, Hulley SB, Cohen JD, et al: Unexpected effects of treating hypertensive men with electrocardiographic abnormalities: A critical analysis . Circulation 1986;73:114-123.Crossref 9. Kriker DM, Rowland E: Clinical value of calcium antagonists in treatment of cardiovascular disorders . J Am Coll Cardiol 1983;1:355-364.Crossref 10. Preibisz JJ, Sealey JE, Acteo RM, et al: Plasma renin activity measurements: An update . Cardiovasc Rev Rep 1982;3:782-787. 11. The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: The 1984 report of the Joint National Committee on detection evaluation and treatment of high blood pressure . Arch Intern Med 1984;144:1045-1057.Crossref 12. Cloher TP, Wheaton PK: Physician approach to the recognition and initial management of hypertension . Arch Intern Med 1986;146:529-533.Crossref 13. Laragh JH: Modification of stepped-care approach to anti-hypertensive therapy . Am J Med 1972;77:78-86. 14. Nicholson JP, Resnick LM, Laragh JH: The antihypertensive effect of verapamil at extremes of dietary sodium intake . Ann Intern Med 1987; 107:329-334.Crossref 15. Hallin L, Anorzin L, Hansson L: Controlled trial of nifedipine and bendroflumethiazide in hypertension . J Cardiovasc Pharmacol 1983;5: 1083-1085.Crossref 16. MacGregor GA, Markandu ND, Smith SJ, et al: Does nifedipine reveal a functional abnormality of arteriolar smooth muscle cell in essential hypertension? The effect of altering sodium balance . J Cardiovasc Pharmacol 1985;7( (suppl 6) );S178-S181.Crossref 17. Benjamin N, Phillips RJW, Robinson BF: Bendrofluazide does not produce any additional fall in blood pressure in hypertensive patients taking verapamil, p 35. Program and abstracts of the Third European Meeting on Hypertension, Basel, Switzerland, February 1988. 18. Leonetti G, Frescio M, Sampiteri L, et al: Does the addition of a diuretic enhance the antihypertensive effect of the calcium antagonist tiapamil? Program and abstracts of the Third European Meeting on Hypertension, Basel, Switzerland, February 1988, p 306. 19. Frishman WH, Zawada ET, Smith LK, et al: Multicenter Comparison of Sustained Release Diltiazem for Mild to Moderate Systemic Hypertension . New York, American Society of Hypertension, 1987, pp 148-272(A). 20. Massie B, McCarthy P, Ramananathan KB, et al: Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide . Ann Intern Med 1987;107:150-157.Crossref 21. Laragh JH, Sealey JE, Niarchos AP, et al: The vasoconstriction-volume spectrum in normotension and in the pathogenesis of hypertension . Fed Proc 1982;41:2415-2483. 22. Hollifield JW, Slaton PE: Thiazide diuretics, hypokalemia and cardiac arrhythmia . Acta Med Scand 1981;647( (suppl) ):67-73. 23. Kiowski W, Bertel O, Erne P, et al: Hemodynamic and reflex mechanisms of acute and chronic antihypertensive therapy with the calcium channel blocker nifedipine . Hypertension 1983;5( (suppl 1) ):170-174.Crossref 24. Hiramatsu K, Yamagishi F, Kubota T, et al: Acute effects of the calcium antagonist, nifedipine, on blood pressure, pulse rate, and the reninangiotension-angiotensin system in patients with essential hypertension . Am Heart J 1982;104:1346-1350.Crossref

Journal

Archives of Internal Medicine – American Medical Association

Published: Jan 1, 1989

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