THIS INSTRUMENT OF RESIGNATION, APPOINTMENT AND ACCEPTANCE (this
“Instrument”), dated as of September 18, 2007 (“Effective Date”), is by and
among CV Therapeutics, Inc., a corporation duly organized and existing under the
laws of the State of Delaware (the “Company”), US Bank National Association, a
national banking association duly organized and existing under the laws of the
United States (the “Successor Trustee” and “Successor Escrow Agent”), and Wells
Fargo Bank, National Association, a national banking association duly organized
and existing under the laws of the United States (the “Resigning Trustee” and
“Resigning Escrow Agent”). Capitalized terms not otherwise defined herein shall
have the same meaning ascribed to such terms in the Indentures (as defined
below) as applicable.

RECITALS

     WHEREAS, pursuant to an indenture dated as of June 18, 2003 (the “2003
Indenture”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $100,000,000 of its 2% Senior
Subordinated Convertible Debentures due 2023 (the “2003 Debentures”);

     WHEREAS, pursuant to an indenture dated as of May 18, 2004 (the “2004
Indenture”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $150,000,000 of its 2.75% Senior
Subordinated Convertible Notes due 2012 (the “2004 Notes”);

     WHEREAS, pursuant to an indenture dated as of July 1, 2005 (the “2005
Indenture”, and collectively with the 2003 Indenture and the 2004 Indenture, the
“Indentures”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $149,500,000 of its 3.25% Senior
Subordinated Convertible Notes due 2013 (the “2005 Notes”, and collectively with
the 2003 Debentures and the 2004 Notes, the “Notes”);

     WHEREAS, pursuant to a pledge and escrow agreement dated as of July 1, 2005
(the “Pledge Agreement”), by and among the Company, the Resigning Trustee, and
Wells Fargo Bank, National Association, in its capacity as escrow agent (the
“Escrow Agent”), the Escrow Agent is holding the Government Securities (as
defined therein) identified on Schedule 1 annexed hereto;

     WHEREAS, the Company appointed the Resigning Trustee as the Paying Agent
and Registrar under each of the Indentures;

     WHEREAS, there is presently issued and outstanding: (i) $100,000,000 in
aggregate principal amount of the 2003 Debentures; (ii) $150,000,000 in
aggregate principal amount of the 2004 Notes; and (iii) $149,500,000 in
aggregate principal amount of the 2005 Notes;

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     WHEREAS, Section 5.9 of each of the Indentures provides that the Trustee
may at any time resign by giving written notice of such resignation to the
Company and the Company shall promptly appoint a successor Trustee;

     WHEREAS, Section 11 of the Pledge Agreement provides that the Escrow Agent
may resign upon 30 days’ written notice to the Company and the Trustee and the
Company shall appoint a successor Escrow Agent;

     WHEREAS, the Resigning Trustee desires to resign as Trustee, Paying Agent
and Registrar and the Company desires to appoint the Successor Trustee as
Trustee, Paying Agent and Registrar to succeed the Resigning Trustee under each
of the Indentures; and

     WHEREAS, the Successor Trustee is willing to accept the appointment as
Trustee, Paying Agent and Registrar under each of the Indentures;

     WHEREAS, the Resigning Escrow Agent desires to resign as Escrow Agent and
the Company desires to appoint the Successor Escrow Agent as Escrow Agent to
succeed the Resigning Escrow Agent under the Pledge Agreement;

     WHEREAS, the Successor Escrow Agent is willing to accept the appointment as
Escrow Agent under the Pledge Agreement;

     NOW, THEREFORE, in consideration of the covenants herein and other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:

     1. Acceptance of Resignation of Resigning Trustee and Resigning Escrow
Agent; Appointment of Successor Trustee and Successor Escrow Agent. Pursuant to
Section 5.9 of each of the Indentures, the Resigning Trustee hereby resigns as
Trustee under the Indentures. The Resigning Trustee also hereby resigns as
Paying Agent and Registrar under each of the Indentures. The Company accepts the
resignation of the Resigning Trustee as Trustee, Paying Agent and Registrar and
hereby appoints the Successor Trustee as Trustee, Paying Agent and Registrar
under each of the Indentures. Pursuant to Section 11 of the Pledge Agreement,
the Resigning Escrow Agent hereby resigns as Escrow Agent under the Pledge
Agreement. The Company accepts the resignation of the Resigning Escrow Agent and
hereby appoints the Successor Escrow Agent as Escrow Agent under the Pledge
Agreement.

     2. Company Representations and Warranties. The Company represents and
warrants to the Successor Trustee that:

a.      It is duly incorporated and validly existing;   b.      The execution
and delivery of this Instrument have been duly authorized  

  by the Company;

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c.      [reserved]   d.      No Event of Default and no other event which, after
notice or lapse of  

time or both, would become an Event of Default, has occurred and is continuing
under any of the Indentures;

e.      Each of the Indentures is in full force and effect;   f.      There is
no action, suit or proceedings pending or, to the best of the  

Company’s knowledge, threatened against the Company before any court or any
government authority arising out of any action or omission by the Company under
any of the Indentures; and

g. This Instrument has been duly authorized, executed and delivered on behalf of
the Company and, assuming due authorization, execution and delivery by the
Successor Trustee, the Successor Escrow Agent, the Resigning Trustee and the
Resigning Escrow Agent, constitutes its legal, valid and binding obligation.

     3. Resigning Trustee Representations and Warranties. The Resigning Trustee
hereby represents and warrants to the Successor Trustee that:

a. No covenant or condition contained in any of the Indentures has been waived
by the Resigning Trustee or, to the best of the knowledge of the Resigning
Trustee, by the Holders of the percentage in aggregate principal amount of the
Notes required by each of the Indentures to effect any such waiver;

b. There is no action, suit or proceeding pending or, to the best of the
knowledge of the Resigning Trustee, threatened against the Resigning Trustee
before any court or governmental authority arising out of any action or omission
by the Resigning Trustee as Trustee, Paying Agent and Registrar under any of the
Indentures;

c. Resigning Trustee has delivered or will deliver to Successor Trustee, as of
or immediately after the Effective Date hereof, all documents in its possession
relating to the trusts created under the Indentures, including all of the
documents listed in Exhibit B hereto, and such other documents reasonably
requested by the Company, the Successor Trustee or the Successor Escrow Agent;

d. The execution and delivery of this Instrument have been duly authorized by
the Resigning Trustee, and this Instrument constitutes the Resigning Trustee’s
legal, valid, binding and enforceable obligation; and

e. The Resigning Trustee certifies that: (i) $100,000,000 in aggregate principal
amount of the 2003 Debentures is outstanding and interest has been paid through
May 15, 2007; (ii) $150,000,000 in aggregate principal amount of the 2004 Notes
is outstanding and interest has been paid through May 15, 2007; and

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(iii) $149,500,000 in aggregate principal amount of the 2005 Notes is
outstanding and interest has been paid through August 15, 2007.

     4. Successor Trustee Representations and Warranties. The Successor Trustee
represents and warrants to the Resigning Trustee and the Company that:

     a. It is eligible to serve as Trustee under each of the Indentures pursuant
to the eligibility requirements set forth therein and the Trust Indenture Act of
1939; and b. It is eligible to serve as Escrow Agent under the Pledge Agreement
pursuant to the eligibility requirements set forth therein.

     5. Acceptance by Successor Trustee and Successor Escrow Agent. Pursuant to
Section 5.9 of each of the Indentures, the Successor Trustee hereby accepts its
appointment as Trustee under each of the Indentures and shall hereby be vested
with all the rights, powers, trusts and duties of the Trustee under each of the
Indentures and with respect to all property and money held or to be held under
each of the Indentures, with like effect as if the Successor Trustee was
originally named as Trustee under each of the Indentures. The Successor Trustee
also hereby accepts it appointment as Registrar and Paying Agent. The Successor
Trustee will perform said rights, powers and duties upon the terms and
conditions set forth in each of the Indentures. Promptly after the execution and
delivery of this Instrument, the Successor Trustee shall cause a notice, a form
of which is annexed hereto as Exhibit A, to be sent to each Holder of the Notes.
Pursuant to Section 11 of the Pledge Agreement, the Successor Escrow Agent
hereby accepts its appointment as Escrow Agent under the Pledge Agreement and
shall be hereby vested with all the rights, powers, trusts and duties of the
Escrow Agent under the Pledge Agreement and with respect to all property and
money held or to be held under the Pledge Agreement, with like effect as if the
Successor Escrow Agent was originally named as Escrow Agent under the Pledge
Agreement.

     6. Board Resolution. The Company hereby certifies that Exhibit C annexed
hereto is true and correct copy of the board resolution that was duly adopted by
the Board of Directors of the Company authorizing the appointment of the
Successor Trustee and the Successor Escrow Agent.

     7. Assignment etc. by Resigning Trustee. Effective on the Effective Date,
the Resigning Trustee hereby confirms, assigns, transfers, delivers and conveys
to the Successor Trustee, as Trustee under each of the Indentures, upon the
trusts expressed in the Indentures, all rights, powers, trusts, privileges,
duties and obligations which the Resigning Trustee now holds under and by virtue
of each of the Indentures, and effective as of such date does hereby pay over to
the Successor Trustee any and all property and moneys held by the Resigning
Trustee under and by virtue of each of the Indentures.

     8. Additional Documentation. The Resigning Trustee, the Resigning Escrow
Agent and the Company, for the purposes of more fully and certainly vesting in
and confirming to the Successor Trustee and the Successor Escrow Agent the
rights, powers, trusts, privileges, duties and obligations hereby assigned,
transferred, delivered and conveyed, agree, upon reasonable request of the
Successor Trustee or the Successor

4

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Escrow Agent, to execute, acknowledge and deliver such further instruments of
conveyance and further assurance and to do such other things as may reasonably
be required by the Successor Trustee or the Successor Escrow Agent.

     9. Choice of Laws. This Instrument shall be governed by the same laws that
govern each of the Indentures.

     10. Counterparts. This Instrument may be executed in any number of
counterparts, each of which, when so executed and delivered, shall be an
original, but all counterparts shall constitute but one Instrument.

     11. Survival of Company’s Obligations to Resigning Trustee and Resigning
Escrow Agent. Notwithstanding the resignation of the Resigning Trustee as
Trustee under each of the Indentures, the Company shall remain obligated under
each of the Indentures to compensate, reimburse and indemnify the Resigning
Trustee in connection with its services as Trustee as provided in each of the
Indentures, and nothing contained in this Instrument shall in any way abrogate
the obligations of the Company to the Resigning Trustee under each of the
Indentures or any lien created in favor of the Resigning Trustee thereunder. The
Company also acknowledges and reaffirms its obligation to the Successor Trustee
set forth in Section 5.8 of each of the Indentures. Notwithstanding the
resignation of the Resigning Escrow Agent as Escrow Agent under the Pledge
Agreement, the Company shall remain obligated under the Pledge Agreement to
compensate, reimburse and indemnify the Resigning Escrow Agent in connection
with its services as Escrow Agent as provided in the Pledge Agreement, and
nothing contained in this Instrument shall in any way abrogate the obligations
of the Company to the Resigning Escrow Agent under the Pledge Agreement or any
lien created in favor of the Resigning Escrow Agent thereunder. The Company also
acknowledges and reaffirms its obligation to the Successor Escrow Agent set
forth in Sections 9 and 10 of the Pledge Agreement.

     12. Notices. All notices, whether faxed or mailed, will be deemed received
when sent pursuant to the following instructions:

TO THE SUCCESSOR TRUSTEE/SUCCESSOR ESCROW AGENT:

  US Bank National Association
60 Livingston Avenue
EP-MN-WS3C
St. Paul, MN 55107-2292
Attn: Rick Prokosch
Phone: 651-495-3918
Fax: 651-495-8097

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TO THE RESIGNING TRUSTEE/RESIGNING ESCROW AGENT:

  Wells Fargo Bank, N.A.
Corporate Trust Services
625 Marquette Avenue; N9311-110
Minneapolis, MN 55479
Attn: Tim Mowdy
Phone: 612-316-1445
Fax: 612-667-9825

TO THE COMPANY:

  CV Therapeutics, Inc.
Attn: General Counsel
3172 Porter Drive
Palo Alto, CA 94304
Fax: 650-858-0388

With a copy (which shall not constitute notice) to:

  Latham & Watkins LLP
140 Scott Drive
Menlo Park, CA 94025
Fax: 650-463-2600
Attn: Alan C. Mendelson, Esq.

     13. Effectiveness. This Instrument and the resignation, appointment and
acceptance effected hereby shall be effective as of the close of business on the
Effective Date; provided, that the resignation of the Resigning Trustee as
Paying Agent and the appointment of the Successor Trustee as Paying Agent under
each of the Indentures shall be effective 10 days after the date first above
written.

[Remainder of page intentionally left blank]

6

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     IN WITNESS WHEREOF, the parties hereto have executed this Instrument as of
the date set forth above.

CV Therapeutics, Inc., as the Company

By_/s/ Louis G. Lange, M.D., Ph.D.
Its_Chairman & CEO

US Bank National Association, as the Successor Trustee and Successor Escrow
Agent

By_/s/ Richard Prokosch
Its_Vice President

Wells Fargo Bank, National Association, as the Resigning Trustee and Resigning
Escrow Agent

By_/s/ Timothy P. Mowdy
Its_Vice President

7

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EXHIBIT A

Notice to Holders of CV Therapeutics, Inc. [insert title of securities]:

We hereby notify you of the resignation of Wells Fargo Bank, National
Association, as Trustee under the Indenture, [insert date of Indenture] pursuant
to which your Notes were issued and are outstanding.

CV Therapeutics, Inc. has appointed US Bank National Association, whose
Corporate Trust Office is located at 60 Livingston Avenue, EP-MN-WS3C, St. Paul,
MN 55107-2292, as successor Trustee under the Indenture, which appointment has
been accepted and become effective.

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EXHIBIT B

     Documents to be delivered by Resigning Trustee to Successor Trustee as to
each of the Indentures (except where noted):

     1. Copy of the most recent of each of the SEC reports delivered by the
Company pursuant to each of the Indentures.

2.      Copy of Indentures.   3.      File of Closing Documents.   4.      U.S.
Treasury Strips held under the Pledge Agreement and identified on Schedule 1  

annexed hereto.

     5. Copy of the most recent Compliance Certificate delivered pursuant to
each of the Indentures.

     6. Certified lists of Noteholders as of the Effective Date, certificate
detail and all “stop transfers” and the reason for such “stop transfers” (or,
alternatively, if there are a substantial number of registered Noteholders, the
computer tape reflecting the identity of such Noteholders).

     7. Copies of any official notices sent by the Trustee to all the
Noteholders of the Notes pursuant to the terms of the Indentures during the past
twelve months, if any.

8.      Notes debt service records.   9.      Trust account statements for
one-year period proceeding the date of this Instrument.   10.      All unissued
Note inventory, if any or DTC FAST held global certificates.   11.     
[reserved]  

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EXHIBIT C

EXHIBIT

To the Minutes of the September 12-13, 2007
Regular Meeting of the Board of Directors
of CV Therapeutics, Inc.

APPOINTMENT OF SUCCESSOR TRUSTEE FOR CONVERTIBLE NOTES

     WHEREAS, the Board of Directors (the “Board of Directors”) of CV
Therapeutics, Inc., a Delaware corporation (the “Company”), has previously
authorized and approved the issuance of the aggregate principal amount of
$100,000,000 of its 2% Senior Subordinated Convertible Debentures due 2023 (the
“2003 Debentures”) pursuant to an indenture dated as of June 18, 2003 (the “2003
Indenture”), by and between the Company and Wells Fargo Bank, National
Association, a national banking association duly organized and existing under
the laws of the United States (“Wells Fargo”); WHEREAS, the Board of Directors
of the Company has previously authorized and approved the issuance of the
aggregate principal amount of $150,000,000 of its 2.75% Senior Subordinated
Convertible Notes due 2012 (the “2004 Notes”) pursuant to an indenture dated as
of May 18, 2004 (the “2004 Indenture”), by and between the Company and Wells
Fargo; WHEREAS, the Board of Directors of the Company has previously authorized
and approved the issuance of the aggregate principal amount of $149,500,000 of
its 3.25% Senior Subordinated Convertible Notes due 2013 (the “2005 Notes,” and
collectively with the 2003 Debentures and the 2004 Notes, the “Notes”) pursuant
to an indenture dated as of July 1, 2005 (the “2005 Indenture,” and collectively
with the 2003 Indenture and the 2004 Indenture, the “Indentures”), by and
between the Company and Wells Fargo; WHEREAS, the Company appointed Wells Fargo
as the paying agent (“Paying Agent”) and registrar (“Registrar”) under each of
the Indentures;

--------------------------------------------------------------------------------

     WHEREAS, Wells Fargo has also acted as escrow agent (“Escrow Agent”)
pursuant to a pledge and escrow agreement dated as of July 1, 2005 (the “Pledge
Agreement”), by and among the Company, Wells Fargo, as Trustee, and Wells Fargo,
in its capacity as Escrow Agent; WHEREAS, Wells Fargo desires to resign as
Trustee, Paying Agent and Registrar and the Company desires to appoint US Bank
National Association, a national banking association duly organized and existing
under the laws of the United States (“US Bank”), as Trustee, Paying Agent and
Registrar to succeed Wells Fargo under each of the Indentures; and WHEREAS,
Wells Fargo desires to resign as Escrow Agent and the Company desires to appoint
US Bank as Escrow Agent to succeed Wells Fargo as Escrow Agent under the Pledge
Agreement; NOW, THEREFORE, BE IT RESOLVED, that the officers of the Company be,
and each of them acting alone hereby is, authorized and empowered in the name
and on behalf of the Company, to designate and appoint (i) US Bank as Trustee,
Paying Agent and Registrar to succeed Wells Fargo under the Indentures and (ii)
US Bank as Escrow Agent to succeed Wells Fargo as Escrow Agent under the Pledge
Agreement; RESOLVED FURTHER, that the officers of the Company be, and each of
them acting alone hereby is, authorized and empowered in the name and on behalf
of the Company to enter into the Instrument of Resignation, Appointment and
Acceptance, by and among the Company, US Bank and Wells Fargo, in substantially
the form attached hereto as Exhibit “-“-I, with such changes to such instrument
as such officers or officer shall determine in their discretion to be necessary,
appropriate or desirable, the execution thereof to be evidence of such
determination, and all such other agreements as may be necessary, appropriate or
advisable in order to effectuate the foregoing designation and appointment;
RESOLVED FURTHER, that such specific additional resolutions as may be (i)
required to be adopted by US Bank as Trustee in connection with the appointment
of US Bank as Trustee for the Notes and the performance by US Bank of its duties
as such and (ii) approved by the officers of the Company or any of them, are
hereby adopted; and

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     RESOLVED FURTHER, that the officers of the Company be, and each of them
acting alone hereby is, authorized and empowered in the name and on behalf of
the Company to appoint US Bank (or such other person as may be approved by such
officer or officers) as Paying Agent and Registrar for the Notes, and to appoint
US Bank as Trustee (or such other person as may be approved by such officer or
officers) as Agent of the Company for the payment of the principal of and
interest on the Notes, and for the purpose of registering any Notes, and
transferring or discharging from registration any Notes, pursuant to the
Indentures.

GENERAL AUTHORITY AND RATIFICATION OF CONSISTENT ACTIONS

     RESOLVED, that any and all actions taken and documents executed by the
officers of the Company, or any person or persons designated and authorized to
act by any of them, prior to the adoption of these resolutions which would have
been authorized thereby had such actions been taken (or documents been executed)
after adoption of these resolutions, are hereby ratified, confirmed, approved
and adopted in all respects; and RESOLVED FURTHER, that the officers of the
Company be, and each of them hereby is, authorized and directed, in the name and
on behalf of the Company, to do or cause to be done all such acts or things and
to sign and deliver, or cause to be signed and delivered, all such documents,
instruments and certificates, as such officer or officers may deem necessary,
advisable or appropriate to effectuate or carry out the purposes and intent of
the foregoing resolutions and to perform the obligations of the Company under
the agreements and instruments referred to therein, the execution and delivery
of such documents, instruments and certificates and the taking of any such
action to be conclusive evidence of the due authorization thereof by the
Company.

12

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EXECUTION VERSION

Exhibit “-“-1

Form of Instrument of Resignation, Appointment and Acceptance

--------------------------------------------------------------------------------

     THIS INSTRUMENT OF RESIGNATION, APPOINTMENT AND ACCEPTANCE (this
“Instrument”), dated as of September 18, 2007 (“Effective Date”), is by and
among CV Therapeutics, Inc., a corporation duly organized and existing under the
laws of the State of Delaware (the “Company”), US Bank National Association, a
national banking association duly organized and existing under the laws of the
United States (the “Successor Trustee” and “Successor Escrow Agent”), and Wells
Fargo Bank, National Association, a national banking association duly organized
and existing under the laws of the United States (the “Resigning Trustee” and
“Resigning Escrow Agent”). Capitalized terms not otherwise defined herein shall
have the same meaning ascribed to such terms in the Indentures (as defined
below) as applicable.

RECITALS

     WHEREAS, pursuant to an indenture dated as of June 18, 2003 (the “2003
Indenture”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $100,000,000 of its 2% Senior
Subordinated Convertible Debentures due 2023 (the “2003 Debentures”);

     WHEREAS, pursuant to an indenture dated as of May 18, 2004 (the “2004
Indenture”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $150,000,000 of its 2.75% Senior
Subordinated Convertible Notes due 2012 (the “2004 Notes”);

     WHEREAS, pursuant to an indenture dated as of July 1, 2005 (the “2005
Indenture”, and collectively with the 2003 Indenture and the 2004 Indenture, the
“Indentures”), by and between the Company and the Resigning Trustee, the Company
issued the aggregate principal amount of $149,500,000 of its 3.25% Senior
Subordinated Convertible Notes due 2013 (the “2005 Notes”, and collectively with
the 2003 Debentures and the 2004 Notes, the “Notes”);

     WHEREAS, pursuant to a pledge and escrow agreement dated as of July 1, 2005
(the “Pledge Agreement”), by and among the Company, the Resigning Trustee, and
Wells Fargo Bank, National Association, in its capacity as escrow agent (the
“Escrow Agent”), the Escrow Agent is holding the Government Securities (as
defined therein) identified on Schedule 1 annexed hereto;

     WHEREAS, the Company appointed the Resigning Trustee as the Paying Agent
and Registrar under each of the Indentures;

     WHEREAS, there is presently issued and outstanding: (i) $100,000,000 in
aggregate principal amount of the 2003 Debentures; (ii) $150,000,000 in
aggregate principal amount of the 2004 Notes; and (iii) $149,500,000 in
aggregate principal amount of the 2005 Notes;

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     WHEREAS, Section 5.9 of each of the Indentures provides that the Trustee
may at any time resign by giving written notice of such resignation to the
Company and the Company shall promptly appoint a successor Trustee;

     WHEREAS, Section 11 of the Pledge Agreement provides that the Escrow Agent
may resign upon 30 days’ written notice to the Company and the Trustee and the
Company shall appoint a successor Escrow Agent;

     WHEREAS, the Resigning Trustee desires to resign as Trustee, Paying Agent
and Registrar and the Company desires to appoint the Successor Trustee as
Trustee, Paying Agent and Registrar to succeed the Resigning Trustee under each
of the Indentures; and

     WHEREAS, the Successor Trustee is willing to accept the appointment as
Trustee, Paying Agent and Registrar under each of the Indentures;

     WHEREAS, the Resigning Escrow Agent desires to resign as Escrow Agent and
the Company desires to appoint the Successor Escrow Agent as Escrow Agent to
succeed the Resigning Escrow Agent under the Pledge Agreement;

     WHEREAS, the Successor Escrow Agent is willing to accept the appointment as
Escrow Agent under the Pledge Agreement;

     NOW, THEREFORE, in consideration of the covenants herein and other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:

     2. Acceptance of Resignation of Resigning Trustee and Resigning Escrow
Agent; Appointment of Successor Trustee and Successor Escrow Agent. Pursuant to
Section 5.9 of each of the Indentures, the Resigning Trustee hereby resigns as
Trustee under the Indentures. The Resigning Trustee also hereby resigns as
Paying Agent and Registrar under each of the Indentures. The Company accepts the
resignation of the Resigning Trustee as Trustee, Paying Agent and Registrar and
hereby appoints the Successor Trustee as Trustee, Paying Agent and Registrar
under each of the Indentures. Pursuant to Section 11 of the Pledge Agreement,
the Resigning Escrow Agent hereby resigns as Escrow Agent under the Pledge
Agreement. The Company accepts the resignation of the Resigning Escrow Agent and
hereby appoints the Successor Escrow Agent as Escrow Agent under the Pledge
Agreement.

     2. Company Representations and Warranties. The Company represents and
warrants to the Successor Trustee that:

a.      It is duly incorporated and validly existing;   b.      The execution
and delivery of this Instrument have been duly authorized  

  by the Company;

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c.      [reserved]   d.      No Event of Default and no other event which, after
notice or lapse of  

time or both, would become an Event of Default, has occurred and is continuing
under any of the Indentures;

e.      Each of the Indentures is in full force and effect;   f.      There is
no action, suit or proceedings pending or, to the best of the  

Company’s knowledge, threatened against the Company before any court or any
government authority arising out of any action or omission by the Company under
any of the Indentures; and

g. This Instrument has been duly authorized, executed and delivered on behalf of
the Company and, assuming due authorization, execution and delivery by the
Successor Trustee, the Successor Escrow Agent, the Resigning Trustee and the
Resigning Escrow Agent, constitutes its legal, valid and binding obligation.

     3. Resigning Trustee Representations and Warranties. The Resigning Trustee
hereby represents and warrants to the Successor Trustee that:

a. No covenant or condition contained in any of the Indentures has been waived
by the Resigning Trustee or, to the best of the knowledge of the Resigning
Trustee, by the Holders of the percentage in aggregate principal amount of the
Notes required by each of the Indentures to effect any such waiver;

b. There is no action, suit or proceeding pending or, to the best of the
knowledge of the Resigning Trustee, threatened against the Resigning Trustee
before any court or governmental authority arising out of any action or omission
by the Resigning Trustee as Trustee, Paying Agent and Registrar under any of the
Indentures;

c. Resigning Trustee has delivered or will deliver to Successor Trustee, as of
or immediately after the Effective Date hereof, all documents in its possession
relating to the trusts created under the Indentures, including all of the
documents listed in Exhibit B hereto, and such other documents reasonably
requested by the Company, the Successor Trustee or the Successor Escrow Agent;

d. The execution and delivery of this Instrument have been duly authorized by
the Resigning Trustee, and this Instrument constitutes the Resigning Trustee’s
legal, valid, binding and enforceable obligation; and

e. The Resigning Trustee certifies that: (i) $100,000,000 in aggregate principal
amount of the 2003 Debentures is outstanding and interest has been paid through
May 15, 2007; (ii) $150,000,000 in aggregate principal amount of the 2004 Notes
is outstanding and interest has been paid through May 15, 2007; and

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(iii) $149,500,000 in aggregate principal amount of the 2005 Notes is
outstanding and interest has been paid through August 15, 2007.

     4. Successor Trustee Representations and Warranties. The Successor Trustee
represents and warrants to the Resigning Trustee and the Company that:

     a. It is eligible to serve as Trustee under each of the Indentures pursuant
to the eligibility requirements set forth therein and the Trust Indenture Act of
1939; and b. It is eligible to serve as Escrow Agent under the Pledge Agreement
pursuant to the eligibility requirements set forth therein.

     5. Acceptance by Successor Trustee and Successor Escrow Agent. Pursuant to
Section 5.9 of each of the Indentures, the Successor Trustee hereby accepts its
appointment as Trustee under each of the Indentures and shall hereby be vested
with all the rights, powers, trusts and duties of the Trustee under each of the
Indentures and with respect to all property and money held or to be held under
each of the Indentures, with like effect as if the Successor Trustee was
originally named as Trustee under each of the Indentures. The Successor Trustee
also hereby accepts it appointment as Registrar and Paying Agent. The Successor
Trustee will perform said rights, powers and duties upon the terms and
conditions set forth in each of the Indentures. Promptly after the execution and
delivery of this Instrument, the Successor Trustee shall cause a notice, a form
of which is annexed hereto as Exhibit A, to be sent to each Holder of the Notes.
Pursuant to Section 11 of the Pledge Agreement, the Successor Escrow Agent
hereby accepts its appointment as Escrow Agent under the Pledge Agreement and
shall be hereby vested with all the rights, powers, trusts and duties of the
Escrow Agent under the Pledge Agreement and with respect to all property and
money held or to be held under the Pledge Agreement, with like effect as if the
Successor Escrow Agent was originally named as Escrow Agent under the Pledge
Agreement.

     6. Board Resolution. The Company hereby certifies that Exhibit C annexed
hereto is true and correct copy of the board resolution that was duly adopted by
the Board of Directors of the Company authorizing the appointment of the
Successor Trustee and the Successor Escrow Agent.

     7. Assignment etc. by Resigning Trustee. Effective on the Effective Date,
the Resigning Trustee hereby confirms, assigns, transfers, delivers and conveys
to the Successor Trustee, as Trustee under each of the Indentures, upon the
trusts expressed in the Indentures, all rights, powers, trusts, privileges,
duties and obligations which the Resigning Trustee now holds under and by virtue
of each of the Indentures, and effective as of such date does hereby pay over to
the Successor Trustee any and all property and moneys held by the Resigning
Trustee under and by virtue of each of the Indentures.

     8. Additional Documentation. The Resigning Trustee, the Resigning Escrow
Agent and the Company, for the purposes of more fully and certainly vesting in
and confirming to the Successor Trustee and the Successor Escrow Agent the
rights, powers, trusts, privileges, duties and obligations hereby assigned,
transferred, delivered and conveyed, agree, upon reasonable request of the
Successor Trustee or the Successor

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Escrow Agent, to execute, acknowledge and deliver such further instruments of
conveyance and further assurance and to do such other things as may reasonably
be required by the Successor Trustee or the Successor Escrow Agent.

     9. Choice of Laws. This Instrument shall be governed by the same laws that
govern each of the Indentures.

     10. Counterparts. This Instrument may be executed in any number of
counterparts, each of which, when so executed and delivered, shall be an
original, but all counterparts shall constitute but one Instrument.

     11. Survival of Company’s Obligations to Resigning Trustee and Resigning
Escrow Agent. Notwithstanding the resignation of the Resigning Trustee as
Trustee under each of the Indentures, the Company shall remain obligated under
each of the Indentures to compensate, reimburse and indemnify the Resigning
Trustee in connection with its services as Trustee as provided in each of the
Indentures, and nothing contained in this Instrument shall in any way abrogate
the obligations of the Company to the Resigning Trustee under each of the
Indentures or any lien created in favor of the Resigning Trustee thereunder. The
Company also acknowledges and reaffirms its obligation to the Successor Trustee
set forth in Section 5.8 of each of the Indentures. Notwithstanding the
resignation of the Resigning Escrow Agent as Escrow Agent under the Pledge
Agreement, the Company shall remain obligated under the Pledge Agreement to
compensate, reimburse and indemnify the Resigning Escrow Agent in connection
with its services as Escrow Agent as provided in the Pledge Agreement, and
nothing contained in this Instrument shall in any way abrogate the obligations
of the Company to the Resigning Escrow Agent under the Pledge Agreement or any
lien created in favor of the Resigning Escrow Agent thereunder. The Company also
acknowledges and reaffirms its obligation to the Successor Escrow Agent set
forth in Sections 9 and 10 of the Pledge Agreement.

     12. Notices. All notices, whether faxed or mailed, will be deemed received
when sent pursuant to the following instructions:

TO THE SUCCESSOR TRUSTEE/SUCCESSOR ESCROW AGENT:

  US Bank National Association
60 Livingston Avenue
EP-MN-WS3C
St. Paul, MN 55107-2292
Attn: Rick Prokosch
Phone: 651-495-3918
Fax: 651-495-8097

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TO THE RESIGNING TRUSTEE/RESIGNING ESCROW AGENT:

  Wells Fargo Bank, N.A.
Corporate Trust Services
625 Marquette Avenue; N9311-110
Minneapolis, MN 55479
Attn: Tim Mowdy
Phone: 612-316-1445
Fax: 612-667-9825

TO THE COMPANY:

  CV Therapeutics, Inc.
Attn: General Counsel
3172 Porter Drive
Palo Alto, CA 94304
Fax: 650-858-0388

With a copy (which shall not constitute notice) to:

  Latham & Watkins LLP
140 Scott Drive
Menlo Park, CA 94025
Fax: 650-463-2600
Attn: Alan C. Mendelson, Esq.

     13. Effectiveness. This Instrument and the resignation, appointment and
acceptance effected hereby shall be effective as of the close of business on the
Effective Date; provided, that the resignation of the Resigning Trustee as
Paying Agent and the appointment of the Successor Trustee as Paying Agent under
each of the Indentures shall be effective 10 days after the date first above
written.

[Remainder of page intentionally left blank]

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     IN WITNESS WHEREOF, the parties hereto have executed this Instrument as of
the date set forth above.

CV Therapeutics, Inc., as the Company

By__________________
Its_____________

US Bank National Association, as the Successor Trustee and Successor Escrow
Agent

By__________________
Its_____________

Wells Fargo Bank, National Association, as the Resigning Trustee and Resigning
Escrow Agent

By__________________
Its____________

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EXHIBIT A

Notice to Holders of CV Therapeutics, Inc. [insert title of securities]:

We hereby notify you of the resignation of Wells Fargo Bank, National
Association, as Trustee under the Indenture, [insert date of Indenture] pursuant
to which your Notes were issued and are outstanding.

CV Therapeutics, Inc. has appointed US Bank National Association, whose
Corporate Trust Office is located at 60 Livingston Avenue, EP-MN-WS3C, St. Paul,
MN 55107-2292, as successor Trustee under the Indenture, which appointment has
been accepted and become effective.

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EXHIBIT B

     Documents to be delivered by Resigning Trustee to Successor Trustee as to
each of the Indentures (except where noted):

     12. Copy of the most recent of each of the SEC reports delivered by the
Company pursuant to each of the Indentures.

13.      Copy of Indentures.   14.      File of Closing Documents.   15.     
U.S. Treasury Strips held under the Pledge Agreement and identified on  

Schedule 1 annexed hereto.

     16. Copy of the most recent Compliance Certificate delivered pursuant to
each of the Indentures.

     17. Certified lists of Noteholders as of the Effective Date, certificate
detail and all “stop transfers” and the reason for such “stop transfers” (or,
alternatively, if there are a substantial number of registered Noteholders, the
computer tape reflecting the identity of such Noteholders).

     18. Copies of any official notices sent by the Trustee to all the
Noteholders of the Notes pursuant to the terms of the Indentures during the past
twelve months, if any.

19.      Notes debt service records.   20.      Trust account statements for
one-year period proceeding the date of this  

Instrument.

21.      All unissued Note inventory, if any or DTC FAST held global
certificates.   22.      [reserved]  

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