Drug-induced hypertension

Michel AziziESH Hypertension Center

Georges Pompidou European Hospital, APHP

Paris Descartes University

Clinical Investigation Center, Inserm

Paris, France

Medications That Can Interfere With Blood

Pressure Control

1. Non-narcotic analgesics

2. Non-steroidal antiinflammatory agents, Selective COX-2 inhibitors

3. Sympathomimetic agents (decongestants, diet pills, cocaine)

4. Stimulants (amphetamine, modafinil…)

5. Oral contraceptives

6. Cyclosporine, Tacrolimus

7. Erythropoietin

8. Venlafaxine, MAO inhibitors, bupropion, and tricyclic agents

9. Antiangiogenic drugs, CYP17A1 inhibitors (prostate cancer)

10. Natural licorice

11. Herbal compounds (ephedra or ma huang)

Calhoun et al Circulation 2008;117:e510

Hypertension risk associated with

antiVEGF treatments

Incidence and risk of HTN with VEGF

signaling pathway inhibitors

Putative mechanisms underlying the development of

hypertension associated with VEGF inhibition

Lankhorst et al. Current Opinion in Pharmacology 2015, 21:7–13

Chemotherapeutic Agents With a

Vascular Side Effect Profile

HTN Angina AMI Takotsubo Stroke PAD Pulm HTN DVT/PE

Monoclonal antibodies X X X X X X VEGFR fusion molecules X X X X Tyrosine kinase inhibitors X X X X X X

Antimicrotubule agents X X X X

Alkylating agents X X X X X Vinca alkaloids X X X mTOR inhibitors X X X Proteasome inhibitors X X X

Vascular disrupting agents X X X X

Joerg Herrmann et al. Circulation. 2016;133:1272-1289

Abiraterone Acetate a CYP17A1 inhibitor

in metastatic prostate cancer

Abiraterone Placebo

(N = 542) (N = 540)

Fluid retention 31% 25%

Hypokalemia 20% 13%

Cardiac disorder 23% 19%

Hypertension 24% 14%

Ryan CJ. Lancet Oncol 2015; 16: 152

Syndrome of mineralocorticoid excess in

patients treated with abiraterone acetate.

• Hypokalemia: 37/38

• HTN: 17/38

• Lower limb edema: 11/38

Attard G. J Clin Endocrinol Metab 2012;97: 507

X

X X

X

Pre-therapy evaluation for chemotherapeutics with

high hypertension risk

Joerg Herrmann et al. Circulation. 2016;133:1272-1289

On-therapy evaluation for chemotherapeutics with

high hypertension risk

Teletransmitted HBP

Joerg Herrmann et al. Circulation. 2016;133:1272-1289

Recommendations for VEGF-inhibitor

induced hypertension

1. Favour AHT with vasodilative drugs

– CCBs (DHP). Avoid diltiazem and verapamil which are CYP 3A4 inhibitors

– ACEIs or ARBs

– Nitrates ?

2. Caution with

– thiazide-type diuretics particularly in patients prone to develop hypercalcemia

– BB: increase in PR and QT intervals

3. Consider AHT drug holidays during the off-antiangiogenic treatment periods

4. Consider antiangiogenic drug holiday or dosage reduction when HTN is refractory to 3

or more AHT or in presence of end-organ damage

5. Antiangiogenic agents should be permanently discontinued in any patient who

experiences a hypertensive crisis

Halimi JM et al. Néphrol Thérap 2008; 4: 602Maitland ML et al. J Natl Cancer Inst 2010;102:596

Hypertension risk associated with

NSAIDs and Coxibs

NSAID- induced Hypertension: Mechanism of Action

Landefeld et al., J Clin Case Rep 2016, 6:7

Heterogeneous relative risk of developing hypertension by individual NSAIDs

Wilson S. J Hypertens 2006; 24:1457–1469

Heterogeneous relative risk of developing hypertension by individual coxib drug

Clara C. J Hypertens 2009; 27:2332–2341

Paracetamol-induced BP increase

Wilson S. J Hypertens 2006; 24:1457–1469

Effervescent paracetamol increases more BP

3-week periods of effervescent paracetamol and noneffervescent paracetamol : 1 g TID)

Effervescent vs. noneffervescent paracetamol ITT Difference in 24-h SBP : + 3.99 mmHg (95% CI: 1.35–6.63PP Difference in 24-h SBP : + 5.04 mmHg (95% CI 1.80– 8.28)

Bentitez-Camps Journal of Hypertension 2018,

Do and don’t do

1) In normotensive, healthy adults who require a short course of NSAIDs, paracetamol and aspirin, the advantages of treatment are likely to outweigh the potential for a minor BP elevation.

2) In hypertensive patients and especially those with CKD: Try to avoid NSAIDS….

• The magnitude of the BP increase is less predictable and may vary with age, baseline BP, type of NSAID and concurrent antihypertensive therapy.

• Exposure to NSAIDs often require intensification of antihypertensive therapy in patients on treatment with ACE-Inhibitors or ARBs, without interfering with the efficacy of Ca-antagonists and central acting drugs

Hypertension risk associated with Cocaine use

Cocaine’s Cardiovascular Pathophysiological Pathways

Havaluk O et al. J Am Coll Cardiol 2017;70:101–13

Approach to CV complications of cocaine abuse

Hypertension risk associated with synthetic estrogens

Oral contraceptive use and risk of hypertension

The risk of hypertension is increased by 13% (95% CI: 3–25) for every 5-year increment in oral contraceptive use

Liu H et al. J Clin Hypertens. 2017;19:1032–1041

Plasma AGT concentration and RAS parameters after intake of 50 μg of EE (▴) or placebo (▵) followed by furosemide and captopril on day 8,

Azizi M. J Clin Endocrinol Metab. 2000;85:4331-7.

Differential regulation of angiotensin peptides in plasma and kidney after estrogen treatment in rats

Campbell DJ. Clin Exp Hypertens. 1997;19:687-98.

Ambulatory blood pressure in mild hypertensive women taking oral estrogen-progestin contraceptives

Contraception: 30 µg of ethinyloestradiol

with 75 µg of gestoden.

Duration of exposure: 3.0 years (range, 4

months to 10 years).

Am J Hypertens. 1995 Mar;8(3):249-53.