Hypertension 2 Flashcards
SPRINT trial
Primary Outcome
Secondary Outcomes
• For those >50yo (without DM/stroke/CHF), “best” BP
targets to reduce CV morbidity and mortality unknown
• Does a lower systolic BP goal (<120 mmHg) reduce
clinical events more than standard goal (<140 mmHg)?
• Randomized, controlled, open-label, conducted in US
• Primary Outcome: all CV events; composite of:
• Non-fatal MI, stroke and acute decompensated HF,
ACS, death from CV cause
• Secondary Outcomes: each component of primary +
renal outcomes in CKD population
Inclusion Criteria Excluded those with: 1. Prior stroke 2. DM 3. CHF 4. Standing SBP<110 5. eGFR<20 mL/min 6. Reside in nursing home
- Age ≥ 50 years
- Baseline systolic BP 130-180 mmHg
- High risk:
a. Age ≥75 years*
b. Clinical cardiovascular disease (CVD)*
c. Subclinical CVD (calcium score, ABI, LVH)
d. CKD (GFR = 20-59 ml/min)*
e. 10-year FRS ≥15%
* Targeted enrolment
ABI = ankle brachial index LVH = left ventricular hypertrophy FRS = Framingham risk score
what was the primary outcome
cumulative hazard Lower than anticipated over 3 years
More risks intensifying therapy
New Thresholds/Targets for the High-Risk Patient
Post-SPRINT: Who does this apply to?
Clinical or sub-clinical cardiovascular disease
OR
Chronic kidney disease (non-diabetic nephropathy, proteinuria <1 g/d, *estimated glomerular filtration rate 20-59 mL/min/1.73m2)
OR
†Estimated 10-year global cardiovascular risk ≥15%
OR
Age ≥ 75 years
There was an increased risk of renal deterioration, potassium abnormalities and hypotension with intensified therapy
• Patients with one or more clinical indications should consent to intensive management…..MONITORING IMPORTANT!!!
New Thresholds/Targets for the High-Risk Patient
Post-SPRINT: Who does this NOT apply to?
Limited or No Evidence:
• Heart failure (EF <35%) or recent MI (within last 3 months)
• Indication for, but not currently receiving, a beta blocker
• Institutionalized elderly Inconclusive Evidence: • Diabetes mellitus • Prior stroke • eGFR < 20 ml/min/1.73m2
Contraindications:
• Patient unwilling or unable to adhere to multiple medications
• Standing SBP <110 mmHg
• Inability to measure SBP accurately
• Known secondary cause(s) of hypertension
Useful Dual Combinations
For additive hypotensive effect in add-on therapy,
combine an agent from
Column 1 with any in Column 2
Beware caveat!!!
Column 1: • ACE Inhibitor
• ARB
• Beta adrenergic blocker
Column 2: • Long-acting calcium channel
blocker *
• Thiazide diuretic
Ratio of Incremental SBP lowering effect at
“standard dose”– Combine or Double?
Should i adda 2nd agent at starting doses before maxmizing doses
Doubling dose of one single drug will get you about 20% lower
Add 2nd drug can double the amount of bp lowering
Dose Response for Antihypertensive
Agents (on sBP in mmHg)
You never double the SD lowering
Decrease by 10% for any bp lowering
If not enough, may need a 2nd drug
Nocturnal Dosing
• Two trials (MAPEC, n=2100 and HYGIA, n=19 084) showed dosing at least 1 antihypertensive drug at hs
reduces composite CV event rate by 45-50%.
• Asleep BP reduced in HS dosing group
• Increased proportion of BP “dipping” at night
• Huge methodological flaws, making results questionable.
• This approach NOT recommended in guidelines.
• BED-MED Study in AB in progress now as well as
TIME trial (UK).
At least one at bedtime Promote nighttime dipping Only 1 study and there are flaws May do it depending of individual data Cautious of diuretics at bedtime, need to go to washroom
Treatment in the absence of compelling indications for specific therapies
2 choices
No other associate risk factors, diseases, CV organ disease
= absense of compelling indicaitons
- Treatment of Systolic/Diastolic hypertension without
other compelling indications - Treatment of Isolated Systolic hypertension without
other compelling indications
First Line Treatment of Adults with Systolic/Diastolic
Hypertension Without Other Compelling Indications
options
Either ACEI or ARB not both
High HR, beta blocker can decrease it
Can be used over 60 for compelling indication
Dihydropyridine CCBs are used over non-dihydro
BB not first line for 60 or above
Other options on left of BB have same degree of bp lowering
40-50 really high bp, may use BB to control high bp
Can still use
**Recommended SPC choices are those in which an ACE-I is combined with a CCB,
an ARB with a CCB, or an ACE-I or ARB with a diuretic
Advantages of Single Pill Combinations (SPCs)
• SPC therapy is associated with better adherence
vs. free combinations1
• A regimen featuring initial prescription of SPC leads to better BP control2
• Initial combination therapy is associated with ↓ risk of CV events than monotherapy
Know which combinations exist and adapt the prescription to 1 combo pill
drugs in thiazide class
Hydrochlorothiazide 12.5-25 mg daily
Indapamide 0.625-2.5 mg daily
Chlorthalidone 12.5-25 mg daily
ACE Inhibitors (ACEi)
Perindopril 4-8 mg daily Ramipril 2.5-20 mg daily Lisinopril 5-40 mg daily Enalapril 2.5-40 mg daily (may dose bid)
Angiotensin Receptor Blockers (ARBs)
Telmisartan 20-80 mg daily
Irbesartan 75-300 mg daily
Valsartan 80-320 mg daily
Candesartan 8-32 mg daily
Calcium Channel Blockers (CCB)
Amlodipine (DHP CCB) 2.5-10 mg daily
Diltiazem (NDHP) 120-360 mg daily
Beta-Blockers
Bisoprolol 2.5-10 mg daily
Metoprolol 12.5-100 mg bid
Thiazides and thiazide-like
whats the difference
Thiazide like is now more prominent in guidelines
Greater degree of bp lowering
Thiazide is shorting acting
Chlorthalidone
Indapamide
Metolazone
which class of drugs?
Thiazide-Like
Hydrochlorothiazide* *this is only agent available in Canada Chlorothiazide Methychlothiazide Polythiazide Bendroflumethiazide
Thiazides
Diuretic Type Meta-Analysis vs. Placebo
what did diuretics reduce?
what did only thiazide-like diuretics reduce
• Both types of diuretics reduced CV events, cerebrovascular
events, and HF
• Only thiazide-like diuretics additionally reduced coronary
events and all-cause mortality
half life of chlorthalidone vs HCTZ
Chlorthalidone Thiazide-like 45-60 hrs
Indapamide Thiazide-like 14-18 hrs
Hydrochlorothiazide Thiazide-type 6-15 hrs
NOTE: Hydrochlorothiazide is available in many combos (so commonly
used); consider BP control if already on (before considering switch).
dosage form chlorthalidone is avail in
Avail in canada only in 50mg tablet but we must split it in half or quartering the tablet
Beta-blockers (BB)
reduction in what?
Compared to placebo or no tx (in those >60):
no reduction in mortality, but reduction in CV
event rate
• Atenolol compared to other 1st line agents:
– increase risk of stroke [HR 1.16, 95%CI 1.04-1.30]
– Not shown when other BB used (smaller #’s)
• ABCD rule….A + B not as synergistic for BP
lowering. Only use if compelling indication.
BB decreases HR
why is ACEi + ARB = Not Good Combo
telmisartan, ramipril, tel + ram barely different after 5 years
Increase in SE does not justify them used together
what are compelling indications
• Compelling indications:
– Ischemic Heart Disease
– Recent ST Segment Elevation-MI or non-ST Segment Elevation-MI
– Left Ventricular Systolic Dysfunction
– Cerebrovascular Disease
– Left Ventricular Hypertrophy
– Non Diabetic Chronic Kidney Disease
– Renovascular Disease
– Smoking
• Diabetes Mellitus
– With Nephropathy
– Without Nephropathy
• Global Vascular Protection for Hypertensive Patients
– Statins if 3 or more additional cardiovascular risks
– Aspirin once blood pressure is controlled
see flowchart on slide 31
ok
Hypertension Treatment in
those with Diabetes
Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg
with Nephropathy and/or CVD or CV risk factors
–> ACEi or ARB
w/o nephropathy:
–> 1. ACEi or ARB
2. . DHP-CCB or Thiazide/thiazidelike diuretic
A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target. Combining an ACEi and a DHP-CCB is recommended.
> 2-drug combinations (preferrable combo: RAASi + DHP-CCB
diabetes mellitus: summary
If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min what will happen?
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB
Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria
If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic
should be substituted for a thiazide diuretic if fluid volume overload
Refractory Hypertension:
Additional Agents
Once first-line drugs/combos considered, if BP still
not at target, use one or more of following:
– Low-dose spironolactone (12.5-50 mg/day) (high serum potassium)
– Alpha blocker (doxazosin 2-16 mg/day)
– Furosemide (if renal failure and fluid retention)
– Clonidine 0.1-0.3 mg po bid
– Hydralazine 10-50 mg po qid
– Methyldopa 250-500 mg po bid-tid
– Nitropatch 0.2-0.8 mg/hour transdermal
– Minoxidil 10-40 mg po daily, dosed bid ($$$)
Pregnancy HTN and goal
Definition: – BP≥140/90 – Non-severe: BP 140/90 but < 160/110 – Severe: BP ≥160/110 Goal: DBP<85 mmHg
Pregnancy
• Drugs of Choice (Grade C):
– Methyldopa – Labetalol – Nifedipine long-acting – Beta-blockers • Second line (Grade D): – Hydralazine, clonidine, thiazides • ACEi and ARB are contra-indicated • Note: BP may go down in pregnancy; best drug is no drug, but need to weigh risk:benefit and monitor closely
Erectile Dysfunction (ED)
Incidence in general population: 8-10%
• Incidence in men with HTN: 15-46%’
• CV-risk predictor
• Associated with hypertension itself; extension of
vascular disease; also associated with smoking
• Drug therapy is associated with ED; disease-induced or drug-induced???
– Beta-blockers (non-selective > cardioselective), diuretics and alpha-blockers felt to be biggest culprits
– CCBs and ACEi/ARBs less-culprit (& may improve ED)
