Welcome

ARB- CCB combination in HTN: uncontrolled with monotherapy

Dr Rajat SR Biswas, MD

Resident Physician

Objectives: To see whether combination is better than monotherapy

Rationale: Pharmacological synergism we get if antihypertensive works on different mechanism

• Types of study: Randomozed Multicenter, single/double blind, parallel group

•Site: Europe, USA and Africa

Patients and methods- >18 to 70 years patients of both sexes with stage ll hypertension or MSSBP>140- <200 or SSDBP >90- <120 mmHg

-Sitting or standing BP at non dominant arm by standard method with ideal BP monitor in accordance with British Hypertension society guideline

-ICH-GCP compliant and Declaration of Helsinki

-Exclusion criteria- more or less same in all studies-Washout period-Initial drug administration then force titration then observation

-Intension to treat basis analysis-Last observation carried forward(POCF)-Common data analysis option(ANOCOVA, t- test or logistic regression)

The Ex-Effects Study: Study Design

The Ex-Effects Study: Patient Disposition

The Ex-Effects Study: Results

Mean change from baseline in mean sitting systolic blood pressure (SBP) according to treatment at weeks 4 and 8 for (A) intent-to-treat population and (B) patients with a baseline mean sitting SBP 180 mm Hg. *P<.05 vs. amlodipine 5 to 10 mg. Standard error of the mean shown in brackets.

The Ex-Effects Study: Results

(A) Mean change from baseline in mean sitting systolic blood pressure (SBP) at Week 4 according to subgroup. *P<.05 vs. amlodipine 5 to 10 mg. Standard error of the mean shown in brackets. (B) Proportion of patients achieving mean sitting SBP<140 mm Hg at Week 4 according to subgroup. Bars represent the 95% confidence intervals. Elderly patients are aged ≥65 years. BMI, body mass index; ISH, isolated systolic hypertension (SBP ≥140 mm Hg and diastolic blood pressure <90 mm Hg2); N is the number of patients in the intention-to-treat population

The Ex-Effects Study: Adverse Events

The Ex-Effects Study: Conclusion

Amlodipine/valsartan 10/160 mg was found to be more effective than amlodipine 10 mg in stage 2 hypertension.

Study Design

Study Results: (A) Distribution of treatment response at week 3

Study Results: (B) Distribution of treatment response at study end

Study Results

Blood pressure reduction by category in patients receiving

amlodipine/valsartan/hydrochlorothiazide

(Aml/Val/HCTZ) triple therapy.

Conclusion

Aml 10 mg/Val 320 mg/HCTZ 25 mg triple therapy is highly effective in reducing BP compared with dual components early in therapy.

Study Design

Study result

Between-Treatment Comparisons for Change From Baseline to End Point in Mean Sitting BP (Intent-to-Treat Population)

Study Results: Mean sitting DBP (A) and SBP (B) by treatment and week

Study Results: Between-treatment comparisons for change from baseline to end point in mean sitting BP (mm Hg) by baseline MSSBP. Data presented are least-square mean changes

Adverse Events:AEs (>2% in Triple-Therapy Group), Regardless of Study-Drug Relationship

Conclusion

This study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg.

EX-FAST Study

EX-FAST Study: Patient Disposition

EX-FAST Study: Results

Incremental antihypertensive effects following a direct switch to amlodipine/valsartan 5/160 mg and 10/160 mg in patients with hypertension previously uncontrolled with monotherapy.

EX-FAST Study: Results

The impact of prior antihypertensive monotherapy in patients switched directly to amlodipine/valsartan on mean change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8 (A) and mean change from baseline in MSSBP over time with amlodipine/valsartan 10/160 mg according to previous antihypertensive monotherapy (B). *BP control is defined as BP <140/90 mm Hg for nondiabetic patients and BP <130/80 mm Hg for diabetic patients.

EX-FAST Study: Results

Incremental antihypertensive effects following a direct switch to amlodipine/valsartan 5/160 mg and 10/160 mg in patients with hypertension previously uncontrolled with monotherapy.

EX-FAST Study: Results

Proportion of diabetic and non-diabetic patients in whom a blood pressure (BP) goal of <140/90 mm Hg was reached with amlodipine/valsartan 5/160 and 10/160 mg at week 8 and week 16 (error bars show 95% confidence intervals).

EX-FAST Study: Adverse Events

EX-FAST Study: Conclusion

Amlodipine/valsartan was found to be an effective and well-tolerated strategy for BP control in a wide range of patients with hypertension not previously controlled by use of a single antihypertensive agent.

The EX-STAND Study

The EX-STAND Study: Study Design

The EX-STAND Study: Study Results

Change in mean sitting systolic blood pressure (MSSBP) (mmHg) from baseline to week 8 (last observation carried forward) by treatment strategy in black patients with stage 2 hypertension (intent-to-treat population).

The EX-STAND Study: Study Results

Change in mean sitting systolic blood pressure (MSSBP) (mmHg) from baseline by week and treatment strategy (intent-to-treat population) in black patients with stage 2 hypertension.

The EX-STAND Study: Study Results

Change in mean sitting systolic blood pressure (MSSBP) (mmHg) from baseline to week 8 by treatment strategy and selected subgroups in black patients with stage 2 hypertension BMI¼body mass index; CI¼confidence interval; ISH¼isolated systolic hypertension. N is the number of intent-to-treat patients of the respective subgroup

The EX-STAND Study: Study Results

Change in mean sitting systolic blood pressure (MSSBP) (mmHg) from baseline to week 12 in black patients with severe hypertension (baseline MSSBP X180mmHg) by treatment strategy. ANCOVA model with treatment, country, and length of washout as factors and baseline MSSBP as covariate.

The EX-STAND Study: Study Results

Change in mean sitting pulse pressure (mmHg) from baseline to week 8 by treatment strategy and age category in black patients with stage 2 hypertension (intent-to-treat population).CI, confidence interval.

The EX-STAND Study: Adverse Events

The EX-STAND Study: Conclusion

Black patients with stage 2 hypertension, combination therapy with amlodipine/valsartan lowered BP more effectively than amlodipine alone with a favorable safety profile comparable to amlodipine monotherapy.

Home message!!!

THANK YOU