Combination of verapamil and beta blockers in systemic hypertension

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<ul><li><p>Combination of Verapamil and Beta Blockers in Systemic Hypertension </p><p>HENRY DARGIE, MB, JOHN CLELAND, MB, IAIN FINDLAY, MB, GORDON MURRAY, PhD, and GORDON MclNNES, MD </p><p>The efficacy and safety of verapamil and proprano- lol were examined in 14 hypertensive patients (mean age 51.2, range 30 to 65) in a double-blind, randomized, crossover study of verapamil, 360 mg, propranolol, 240 mg, these 2 formulations in combi- nation and placebo, each given for 4 weeks. Supine blood pressure, heart rate, atrioventricular conduc- tion (PR interval) and left ventricular function were measured. All treatments reduced diastolic blood pressure (mean f standard deviation) (p </p></li><li><p>into the study. The treatments were verapamil, 120 mg The calcium-channel blockers are a beterogenous 3 times a day, propranolol, 80 mg 3 times a day, verapa- group of compounds; verapamil, unlike nifedipine, mil, 120 mg 3 times a day plus propranolol, 80 mg 3 has additional properties in delaying conduction in the times a day, and placebo; each was given for 4 weeks. atrioventricular node,7 which is the basis for its SUC- On completion of each treatment, blood pressure at cessful use in supraventricular tachycardias. This rest and heart rate (supine and standing) were mea- property is shared by p blockers and in our study both sured using a Bosomat II automatic blood pressure propranolol and verapamil prolonged atrioventricular recorder (Bosch and Sohn). Heart rate and cardiac nodal conduction as inferred from the increase in PR rhythm were assessed by resting electrocardiogram interval. This effect was greater with the combination from which the PR interval was calculated and by 24- than either drug alone but no significant pauses or hour ambulatory electrocardiographic monitoring us- episodes of more serious conduction disturbances oc- ing the Oxford Medilog I recorder and the Reynolds curred. We would regard these observations as the medical pathfinder analyzer. LV internal dimen- expected consequence of the clinical pharmacologic sions were recorded using M-mode echocardiography profiles of verapamil and propranolol. Their clinical from which fractional shortening was calculated. The significance in patients with normal cardiac function results of the treatments were compared using repeat- as in this group of hypertensive patients is uncertain. ed measures analysis of variance and paired t tests. In patients with impaired IX function or disturbed </p><p>Results cardiac conduction, however, these effects could be of concern. </p><p>Supine blood pressures are shown in Figure 1. All In our studies in both hypertensive and ischemic treatments significantly decreased the diastolic blood heart disease we have used doses of @ blockers and pressure but the effect of the combination of verapa- verapamil that, conventionally, could be described as mil and propranolol was significantly greater than ei- maximal. In clinical practice the addition of lower ther drug alone (p </p></li><li><p>82D A SYMPOSIUM: CALCIUM ANTAGONISTS IN HYPERTENSION-FOCUS ON VERAPAMIL </p><p>In summary, the combination of propranolol and verapamil isvery effective in lowering blood pressure, but careful monitoring must be advised until the safety of this combination has been assessed in a large pa- tient population. The theoretical advantage of using a ,6 blocker with partial agonist activity should not be implemented clinically until proven in suitably de- signed clinical trials. </p><p>References 1. Fleckenstein A. Specific pharmacology of calcium in myocardium cardiac pacemakers and vascular smooth muscle. Annu Rev Pharmacol Toxic01 </p><p>1977;17:149-166. 2. Lewis GJR, Morley KD, Lewis BM, Bones PJ. The treatment of hyperten- sion with verapamil. NZ Med J 1978;87:352-354. 3. Harris L, Dargie HJ, Lynch PG, Bulpitt CJ. Krikler DM. Blood pressure and heart rate in patients with ischaemic heart disease receiving nifedipine and propranoloi. Br Med J 1982;284:1148-1151. 4. Findlay IN, Gillen G, Elliott AT. Dargie HJ. The treatment of ongina pectoria with calcium channel and p-blockers: efficacy and effect on cardiac function. JACC 1984;3:482. 5. Dargie HJ, Lynch PC, Krikler DM, Harris L, Krikler S. Nifedipine and propranolol in angina pectoris: a beneficial drug interaction. Am J Med 1981;71:676-682. 6. Findlay IN, Dargie HJ. The effects of nifedipine, atenolof and that combi- nation on left ventricular function. Postgrad Med 1 1983;59:suppf 2:70-73. 7. Rowland E. Evans T, Krikler DM. Effect of nifedipine on otrioventriculor conduction as compared with verapamil. Br Heart f 1979;42:124-127. </p></li></ul>