Pre-ALLHAT Drug UsePre-ALLHAT Drug Use

IMS Health NDTI, 1978-1992IMS Health NDTI, 1978-1992

00

1010

2020

3030

4040

5050

6060

19781978

YearYear

% o

f T

reat

ed P

atie

nts

on

Med

icat

ion

% o

f T

reat

ed P

atie

nts

on

Med

icat

ion CCBs

Beta BlockersDiureticsACE Inhibitors

CCBsCCBs

ß-Blockersß-Blockers

ACE InhibitorsACE Inhibitors

DiureticsDiuretics

19801980 19821982 19841984 19861986 19881988 19901990 19921992

BackgroundBackground• In addition to their BP lowering potential all In addition to their BP lowering potential all

antihypertensive agents have other antihypertensive agents have other important mechanisms of action, important mechanisms of action, indications, and side effects.indications, and side effects.

• These actions may convey benefits or risks These actions may convey benefits or risks independent of BP loweringindependent of BP lowering

• By having a common BP goal for all By having a common BP goal for all treatment arms, ALLHAT aimed to evaluate treatment arms, ALLHAT aimed to evaluate the health effects of these non-BP actionsthe health effects of these non-BP actions

ALLHAT

Overall PurposeOverall Purpose

To determine whether the newer, To determine whether the newer, more costly antihypertensive more costly antihypertensive drugs - CCBs, ACE inhibitors and drugs - CCBs, ACE inhibitors and alpha-blockers - are superior to alpha-blockers - are superior to the older, less expensive diuretics the older, less expensive diuretics in preventing CV complications in preventing CV complications of hypertension.of hypertension.

ALLHAT

Health Effects of DiureticsHealth Effects of Diuretics

Low-dose thiazide-type diuretic-based Low-dose thiazide-type diuretic-based treatment in large clinical trials has been treatment in large clinical trials has been shown to reduce the risks of:shown to reduce the risks of:

Event reduction %Event reduction %StrokeStroke 34 34

Heart failureHeart failure 42 42CHDCHD 28 28CVD mortalityCVD mortality 24 24Total mortalityTotal mortality 10 10

ALLHAT

Psaty et al., JAMA 1997;277:739-45Psaty et al., JAMA 1997;277:739-45

StrengthsStrengths• Largest hypertension trial ever Largest hypertension trial ever

(n=42,418); practice-based(n=42,418); practice-based• Diverse study populationDiverse study population• High methodologic standardsHigh methodologic standards• Independent sponsorship and conductIndependent sponsorship and conduct• Conclusions based on 10,834 Conclusions based on 10,834

cardiovascular eventscardiovascular events

ALLHAT

ImplicationsImplications1.1. Selection of first-line drugSelection of first-line drug

2.2. Selecting treatments for particular patientsSelecting treatments for particular patients

3.3. Drug cost and health benefitDrug cost and health benefit

● To patients

● To society

4.4. Design of future hypertension trialsDesign of future hypertension trials

5.5. Impact on treatment guidelinesImpact on treatment guidelines

ALLHAT

Selection of 1Selection of 1stst-line -line Drug - ConclusionsDrug - Conclusions

Among antihypertensive drugs, thiazide-like Among antihypertensive drugs, thiazide-like diuretics were unsurpassed in:diuretics were unsurpassed in:• long-term drug adherencelong-term drug adherence• controlling elevated blood pressurecontrolling elevated blood pressure

and were superior to other therapies inand were superior to other therapies in• preventing one or more forms of preventing one or more forms of

cardiovascular eventscardiovascular events• having lower drug costhaving lower drug cost

ALLHAT

ImplicationsImplications

Selection of 2Selection of 2ndnd-line -line Drug(s) - Type of Add-onDrug(s) - Type of Add-on

• Large proportion of hypertensive Large proportion of hypertensive patients require additional drug(s) for patients require additional drug(s) for BP controlBP control

• No direct comparison of 2No direct comparison of 2ndnd-line drugs in -line drugs in ALLHATALLHAT

• Optimal type of add-on agent unknownOptimal type of add-on agent unknown• Need for large trials comparing different Need for large trials comparing different

classes of agents added to diureticsclasses of agents added to diuretics

ALLHAT

ImplicationsImplications

Source: NDTI -- IMS HEALTH

2002 Use of Antihypertensive Medications, Proportionof Drug-Treated Patients by Drug Class

0%0%

10%10%

20%20%

30%30%

40%40%

ACE-ACE-InhibitorsInhibitors

CalciumCalciumChannelChannelBlockersBlockers

DiureticsDiuretics Beta-Beta-BlockersBlockers

ARBsARBs

% P

atie

nts

%

Pat

ien

ts

37%37%

27%27%

20%20% 20%20% 19%19%

Selecting Treatments Selecting Treatments for Particular Patients Ifor Particular Patients I

Benefits of diuretics generalizable to:Benefits of diuretics generalizable to:• Men and womenMen and women• Age group <65 and Age group <65 and >> 65 yrs 65 yrs• Blacks and non-blacksBlacks and non-blacks• Diabetics and non-diabeticsDiabetics and non-diabetics• Presence and absence of other co-Presence and absence of other co-

morbiditymorbidity

ALLHAT

ImplicationsImplications

Diuretics are better than:Diuretics are better than:

- ACEIs (lisinopril) for patients at high risk of ACEIs (lisinopril) for patients at high risk of CVD events, especially heart failure, as well CVD events, especially heart failure, as well as for African-Americans at risk of strokeas for African-Americans at risk of stroke

- Alpha-blockers (doxazosin) for patients at Alpha-blockers (doxazosin) for patients at high risk of heart failure, stroke, angina and high risk of heart failure, stroke, angina and coronary revascularizationscoronary revascularizations

- CCBs (amlodipine) for patients at high risk of CCBs (amlodipine) for patients at high risk of developing heart failuredeveloping heart failure

ALLHAT

ImplicationsImplicationsSelecting Treatments Selecting Treatments

for Particular Patients IIfor Particular Patients II

Selecting Treatments for Selecting Treatments for Patients - ConclusionsPatients - Conclusions

Thiazide-type diuretics should be Thiazide-type diuretics should be considered for nearly all patients with considered for nearly all patients with hypertension:hypertension:• Untreated patientsUntreated patients• Inadequately controlled patients on Inadequately controlled patients on

non-diuretic agent(s)non-diuretic agent(s)• Controlled patients on non-diuretic Controlled patients on non-diuretic

agent(s) unless compelling agent(s) unless compelling indication exists for another agentindication exists for another agent

ALLHAT

ImplicationsImplications

Drug Cost to Patient Drug Cost to Patient (U.S. 2002)(U.S. 2002)

ChlorthalidoneChlorthalidone $ 36$ 36

AmlodipineAmlodipine $679$679

LisinoprilLisinopril - branded- branded $533$533

- generic**- generic** $280$280*Drugstore.com (exclusive of dispensing fee) **available 3*Drugstore.com (exclusive of dispensing fee) **available 3rdrd quarter 2002quarter 2002

AnnualAnnual

ImplicationsImplications

ALLHAT

Drug Cost to SocietyDrug Cost to Society

ACEIsACEIs $280-$280- 12.712.7 $3,556-$3,556- 533533 6,769 6,769

CCBsCCBs $679$679 9.3 9.3 $6,315 $6,315

DiureticsDiuretics $ 36$ 36 6.9 6.9 $ 248$ 248

ALLHAT

AverageAverage AnnualAnnual

DrugDrugCost/Pt*Cost/Pt*

No. ofNo. ofAnnualAnnualUsers**Users**

TotalTotalDrugDrug

Cost**Cost**

*price of largest selling drug/class (2002) **in million*price of largest selling drug/class (2002) **in million

ImplicationsImplications

Excess CV EventsExcess CV Events

ACEIs ACEIs Comb CV Comb CV 2.3%2.3% 12.7 12.7 48,70048,700EventsEvents

CCBsCCBsCHF CHF 2.5%2.5% 9.3 9.3 38,80038,800

ALLHAT

6-yr6-yrExcessExcess

TotalTotalUsers*Users*

ExcessExcessevents/yr**events/yr**

*in million*in million **concomitant use of diuretics may reduce**concomitant use of diuretics may reducethese numbers by up to 20%these numbers by up to 20%

ImplicationsImplications

Design of Design of Hypertension TrialsHypertension Trials

Thiazide-like diuretics, in low to Thiazide-like diuretics, in low to moderate dose, should be the moderate dose, should be the treatment control group of future treatment control group of future comparative trials in patients with comparative trials in patients with hypertension.hypertension.

ALLHAT

ImplicationsImplications

Treatment GuidelinesTreatment Guidelines

Thiazide-like diuretics, in low to Thiazide-like diuretics, in low to moderate dose, should be the moderate dose, should be the guideline-recommended first-line guideline-recommended first-line drug treatment for nearly all patients drug treatment for nearly all patients with hypertension.with hypertension.

ALLHAT

ImplicationsImplications

Conclusions IConclusions I

• The benefit of diuretics as first-line The benefit of diuretics as first-line therapy applies to nearly all patients therapy applies to nearly all patients with hypertensionwith hypertension

• Diuretics are superior or unsurpassed Diuretics are superior or unsurpassed in reducing the risks of cardiovascular in reducing the risks of cardiovascular complicationscomplications

• Diuretics are the least expensive Diuretics are the least expensive agents for treating hypertensionagents for treating hypertension

ALLHAT

ImplicationsImplications

Conclusions IIConclusions II• Translating the ALLHAT findings into Translating the ALLHAT findings into

practice will reduce the financial cost of practice will reduce the financial cost of antihypertensive drugs and reduce the antihypertensive drugs and reduce the societal burden of CV complicationssocietal burden of CV complications

• Future comparative hypertension trials Future comparative hypertension trials should use diuretics as the control group should use diuretics as the control group or base therapyor base therapy

• Treatment guidelines are being revised to Treatment guidelines are being revised to reflect the ALLHAT findingsreflect the ALLHAT findings

ALLHAT

ImplicationsImplications