Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension

Abstract

A factorial design was applied in this multicenter, double-blind, placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy, to evaluate safety, and to determine the effects on quality of life (QOL) of both drugs, alone and in combination. The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure (BP) of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout, were randomized to one of six treatment groups for 4 weeks of active treatment. Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo. The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only. The total number of adverse events reported was similar for all six treatment groups. QOL scores were unchanged from baseline and not different between treatment groups. The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL. Thus, combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy.

Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy

“…Headaches, which are significantly less common in treated persons, are excluded from this analysis. r53,r56,r63;r22,r25,r29,r36,r39,r92,r95,r96,r105,r108,r114,r119,r120;ACE inhibitors,r15,r20,r21,r23,r26,r34,r66,r203,r9,r19,r30,r139,r140,r158,r195,r253,r254;r9,r24,r28,r31,r65,r79,r82,r136,r138,r170,r171,r182,r215,r216, This varied; some symptoms were not recorded in every trial. c Not statistically significant; however, the upper CI is informative.…”

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“…Advantages of factorial design are many, viz., (i) it requires less resource, (ii) effects of each factor as well as interaction between the factors can be estimated systematically, and (iii) there is experimental information in a larger region of the factor space [Czitrom, 1999]. Reports on the use of statistical design for the optimization of doses in animal models are few; by factorial design, an earlier report has shown the use of a successful combination of verapamil and enalapril in the treatment of mild to moderate hypertension [Levine et al, 1995].…”

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“…[3][4][5][6] This is moreover no isolated phenomenon; the inclusion of such periods has been described as routine or even ritual. 7 8 To understand what is ethically troubling about this practice, we need to examine the essential characteristics of both placebos in general, and the notion of "single blinding" in particular.…”