5.2.2 Managing hypertension

5.2.2 Managing hypertension^1,2

More than 80% of patients treated with TKI develop hypertension – either de novo or worsening of previously controlled high BP. Patients who develop hypertension tend to have a better and longer response to TKI. Risk factors for the development of hypertension during TKI:

Age > 65 years
History of hypertension
History of vascular disease (AMI, cerebral stroke, peripheral vascular disease)
Diabetes mellitus

Rapid development of hypertension, during TKI in patients not previously known to have hypertension, can cause acute organ damage, incl. TCI/cerebral stroke, AMI, heart failure and acute renal impairment. It is therefore important that blood pressure is well-regulated at the start of TKI and to instruct patients to:

Measure their blood pressure frequently – especially at the start of treatment
Contact your own doctor or the department if BP increases and BP > 150/90.

CTC AE grade

How to manage

Follow-up

Grade 1:
Systolic BP 120–139 mmHg or diastolic BP 80–89 mmHg.

Grade 1:
Maintain TKI dose. Intervention not indicated.

Grade 1:
Instruct the patient to measure BP at home weekly (BP record to be brought along to each consultation).

Grade 2:
Systolic BP 140–159 mmHg or diastolic BP 90–99 mmHg if previously within normal range.
Recurrent or persistent (>24 hours) or symptomatic rise of > 20 mmHg (diastolic)

Grade 2:
Maintain TKI dose. Monotherapy indicated (see below).

Grade 2:
See above.
Complete diary for daily BP measurement. Provide advice to the patient: 1) exercise 2) weight loss 3) avoid smoking 4) salt restriction

Grade 3:
Systolic BP > 160 mmHg or diastolic BP > 100 mmHg. Requires more than one medication or more intensive treatment than previously.

Grade 3:
1) Maintain dose of TKI if patient is asymptomatic. Intensify the antihypertensive therapy (see below).
2) If the patient is symptomatic, TKI should be paused.
3) TKI may be resumed at a reduced dose at grade ≤ 2.
4) In the event of recurrence of grade 3 hypertension after resumption, the TKI should be paused and the patient referred to the cardiology department for further BP regulation. TKI can be resumed at a further reduced dose after conference with a specialist.

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Grade 4:
Life-threatening consequences (e.g. hypertensive crisis).

Grade 4:
1) Pause TKI. 2) Consider hospitalisation if the patient is symptomatic or BP is persistent >220/120. 3) TKI may be resumed at a reduced dose at grade ≤ 2.

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Pharmacological treatment for hypertension (according to recommendations from the Danish Society of Cardiology):

Uncomplicated hypertension (Hypertension without sequelae). Free choice between 4 groups of medicinal products

Thiazides and thiazide-like substances (other than hydrochlorothiazide should be used in preference)
Dihydropyridine-type calcium antagonists (amlodipine). Calcium antagonists of non-dihydropyridine type are contraindicated with TKI due to interaction
ACE inhibitors (Not 1st choice in eGFR <30 ml/min)
Angiotensin II antagonists (Not 1st choice in eGFR <30 mL/min and should not normally be combined with ACE inhibitors)

Beta-blockers, especially atenolol, are no longer considered routine first-line medicinal products. Currently, it is recommended to reserve beta-blockers for patients who, in addition to hypertension, have a supplementary indication for beta-blockade, e.g. ischemic heart disease, rapid atrial fibrillation or heart failure. Likewise if a symptomatic benefit can be obtained by beta blockade (tremors, extrasystole or migraine).

Combination therapy: Combination therapy with 2–3 medicinal products will often be necessary to achieve the recommended goals by combining medicinal products from the first choice group. Beta-blockers, alpha-blockers, centrally acting medicinal products may be added if blood pressure is not well controlled on a combination of the above-mentioned medicinal products.

Hypertension with sequelae (special groups)

SPECIAL GROUPS	CHOICE OF DRUG
Elderly patients	Careful up-titration is advised. Sitting and standing blood pressure will be measured prior to up-titration to detect orthostatic drop in blood pressure. You can choose freely among the 4 recommended drug groups, and competing disorders usually determine the choice of drug.
Diabetes mellitus	ACE inhibitor or an angiotensin II antagonist should be included in the treatment. There is usually a need for at least two-drug treatment.
Ischaemic heart disease	Beta-blocker, calcium channel blocker and ACE inhibitor should be preferred, possibly in combination.
Cardiac failure without symptoms	ACE inhibitor, but angiotensin II antagonist is recommended for ACE inhibitor intolerance.
Cardiac failure with symptoms	ACE inhibitor, but in the case of ACE inhibitor intolerance, angiotensin II antagonist, with the addition of an alpha/beta-blocker (carvedilol) or beta-blocker (metoprolol, nebivolol or bisoprolol) is also recommended at normal or low blood pressure. In addition, aldosterone antagonist if tolerated and loop diuretics as symptomatic treatment.
After stroke	The treatment is the same as for uncomplicated hypertension (hypertension without sequelae), where you can choose freely from the four recommended drug groups. The most positive results in reducing the risk of recurrence have been achieved with a combination of ACE inhibitor and thiazide.
Chronic kidney disease	ACE inhibitor or angiotensin II antagonist, possibly in combination with diuretics, is the initial treatment. For eGFR < 30 ml/min, treatment should be discussed with a nephrologist.