# Presentation: 679410

## Clinician’s Perspective

**FDA Cardiovascular and Renal Drugs****Advisory Committee Meeting**
*July 19, 2002*

**Henry Black, M.D., FACP****Rush Medical College, Rush University****Rush-Presbyterian-St. Luke’s Medical Center****Chicago, IL**

## Given omapatrilat’s greater efficacy, does it add value to currently available regimens?

## Goal Of Antihypertensive Therapy

******140 mmHg *****and***** ******** 90 mmHg**
****** ****130 mmHg *****and***** ******** 85 mmHg for diabetics, patients with HF and those with CRF**
****** ****125 mmHg *****and***** ******** 75 mmHg for those with ******** 1 gram of proteinuria**
***Goal is not dependent on age, gender or other forms of co-morbidity***

**JNC VI. *****Arch Intern Med*****. 1997;157:2413-2446. **

## BP Control in the LIFE Trial

**Dahlof B, et al.  *****Lancet***** 2002;359:995-1003.**

**Baseline BP****                    **** 174 / 98                                ****	****   175 / 98                ****Mean Follow-up              4.8 years****	****  4.8 years**

**Losartan**
**(n = 4605)**

**Atenolol**
**(n = 4588)**

**Fraction with Controlled BP**
**  ****(%)**

## BP Control in Diabetic Patients in the LIFE Trial

**SBP ********140 mmHg**

**DBP ******** 90 mmHg**

**Lindholm LH, et al.  *****Lancet***** 2002;359:1004-1010.**

**Baseline BP****             ****176 / 97                                          177 / 96**
**Mean Follow-up     4.7 years                                        4.7 years**

**Losartan**
**(n = 586)**

**Atenolol**
**(n = 609)**

**Fraction with Controlled BP**
**  ****(%)**

## BP Control in ALLHAT

**Study Duration**

***ALLHAT***

**SBP ******** 140 mmHg**

**DBP******** 90 mmHg**

**SBP ******** 140 mmHg**
**and  DBP******** 90 mmHg**

**% with Controlled BP**

**n = 42,408**

## BP Control in CONVINCE

**% with Controlled BP**

**Baseline****(n = 16,412)**

**EOT****(n = 15,446)**

**12 mo****(n = 14,576)**

**24 mo****(n = 12,263)**

**36 mo****(n = 4938)**

**Study Duration **

**Updated from Black HR, et al. *****Hypertens*****ion, 2001; 37:12-18.**

## Distribution of Treatment Regimensin the CONVINCE Study

**Fraction of Subjects (%)**

**End of****Titration**

**6****Months**

**12****Months**

**18****Months**

**24****Months**

**30****Months**

**Distribution of Treatment Regimens****in the CONVINCE Study**

**Open****Label**

**Step III**

**Step II**

**Step I**

**Step 1:****	****COER verapamil or HCTZ or Atenolol**
**Step 2:****	****COER verapamil and HCTZ or Atenolol and HCTZ**
**Step 3:****	****Step 2 and another antihypertensive drug**
**Open Label:****  Any regimen not including blinded COER verapamil, HCTZ or atenolol**

**Black HR, et al. *****Hypertension*****. 2001; 37:12-18.**

**Notes:**
During follow-up, there was a continuous intensification of therapy, as fewer subjects stayed on single-drug therapy, and more moved to multiple-agent treatment. There was also a trend for more subjects to change to open-label (i.e., non-blinded) therapy.
At "End of Titration," fully 60% of subjects were taking only single-drug therapy, but by 6 months after randomization, this proportion had fallen to only 48%.
The proportion of CONVINCE participants using Step II therapy (COER-verapamil + HCTZ or atenolol + HCTZ) was rather more constant at about 20%.
Step III therapy (blinded study medication + at least one open-label  antihypertensive drug, preferably an ACE-inhibitor) became more common as the study progressed: at "End of Titration" only 11.5% were receiving Step III treatment. This proportion increased monotonically throughout the study, such that by 36 months, 23% were taking Step III treatment.
Open-Label treatment (using other than blinded study medication) also increased from 11% to 31% over the 36 months of follow-up; this was the primary reason for the increase in sample size from 15,000 to 16,600.

## Blood Pressure at Goal (n = 437)( 140 mmHg /  90 mmHg)

**Initial Visit**

**Visit Analyzed**

**Blood Pressure at Goal (n = 437)****(******** 140 mmHg / ******** 90 mmHg)**

## Blood Pressure Goals of Diabetics (n = 87) Distributed by Guideline Recommendations

**SBP at Goal**

**DBP at Goal**

**Both at Goal**

**% at Goal**

**Blood Pressure Goals of Diabetics (n = 87) ****Distributed by Guideline Recommendations**

## Multiple Drug RegimensDiabetics

**All (n = 437)**

**Diabetic (n = 87)**

**Multiple Drug Regimens****Diabetics**

**0 Drugs**

**1 Drug**

**2 Drugs**

**% on Drug Regimen**

**3 or More**

## Drug Class DistributionDiabetics

**Drug Class Distribution****Diabetics**

**Diuretic**

**% on Drug Class**

**Calcium****Antagonist**

**ACE-I**

******-blocker**

******-blocker**

**ARB**

**Central**

**Minoxidil**

## Conclusion

**We fail to reach systolic blood pressure goal in a substantial number of patients despite currently available regimens**
**Regimens that include omapatrilat will greatly improve our ability to achieve systolic blood pressure goals**