tim mach

1. Lipid Effects of Antihypertensive
Medications
Matthew Sorrentino MD FACC FASH
Professor of Medicine
Cardiology
University of Chicago Medicine
12 May, Nha Trang City, Vietnam, VSH Conference

2. • Introduced New Blood Pressure Definitions
• Calculation of CVD Risk to determine Blood Pressure
Treatment Goals
• Four Antihypertensive Classes as First Line Medications
(Beta-Blockers no longer 1st Line)
• Outlined Proper Blood Pressure Measurement Technique
• Emphasized Lifestyle Modification – Diet and Exercise
2017 ACC/AHA Hypertension Guidelines
ACC = American College of Cardiology
AHA = American Heart Association
CVD = Cardiovascular Disease
Whelton PK et al., Htn 2017 Nov 13 Epub

3. Categories of BP in Adults*
BP Category SBP DBP
Normal <120 mmHg and <80 mmHg
Elevated 120–129 mmHg and <80 mmHg
Hypertension
Stage 1 130–139 mmHg or 80–89 mmHg
Stage 2 ≥140 mmHg or ≥90 mmHg
*Individuals with SBP and DBP in 2 categories should be
designated to the higher BP category.
BP indicates blood pressure (based on an average of ≥2 careful
readings obtained on ≥2 occasions, as detailed in DBP, diastolic
blood pressure; and SBP systolic blood pressure.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the
Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults,
Published on November 13, 2017, available at: Hypertension and Journal of the
American College of Cardiology.

4. Normal BP
(BP <120/80
mm Hg)
Promoteoptimal
lifestyle habits
Elevated BP
(BP 120–129/<80
mm Hg)
Stage 1 hypertension
(BP 130–139/80-89
mm Hg)
Nonpharmacologic
therapy
(Class I)
Reassess in
3–6 mo
(Class I)
Reassess in
1 mo
(Class I)
Nonpharmacologic
therapy and
BP-lowering medication
(Class I)
Reassess in
1 y
(Class IIa)
Clinical ASCVD
orestimated 10-y CVDrisk
≥10%*
YesNo
Nonpharmacologic
therapy
(Class I)
BP thresholds and recommendations for treatment and follow-up
Nonpharmacologictherapy
and
BP-lowering medication†
(Class I)
Reassess in
3–6 mo
(Class I)
Stage 2 hypertension
(BP ≥ 140/90 mm Hg)
Blood Pressure (BP) Thresholds and Recommendations
for Treatment and Follow-Up
Whelton PK et al., Htn 2017 Nov 13 Epub

5. Treatment of Hypertension
Four Medication classes as First Line Therapy for Hypertension
ACE Inhibitors
Angiotensin Receptor Blockers (ARB)
Calcium Channel Blockers
Thiazide Diuretics
Beta-Blockers no longer First Line Therapy unless a compelling
Indication for their use

6. 0 1 2
Meta-analysis of Beta-blockers in Hypertension:
Outcome Data for Atenolol vs Non-beta-blocker
Antihypertensive Therapy
1.26 (1.15-1.38)
1.05 (0.91-1.21)
1.08 (1.02-1.14)
Stroke
MI
All-cause mortality
Lindholm LH et al. Lancet. 2005;366:1545-1553.
Increased riskDecreased risk

7. ACCOMPLISH
• Primary endpoint (CV mortality, stroke, MI,
revascularization, unstable angina,
resuscitation from death) 9.6% in
amlodipine/benazepril arm, compared
with 11.8% in HCTZ/benazepril arm (p <
0.001)
• MI was reduced with
amlodipine/benazepril arm
(p = 0.04); CV mortality and stroke, similar
• Adverse events were similar
Trial design: Patients with hypertension were randomized to fixed dose
amlodipine/benazepril or hydrochlorothiazide (HCTZ)/benazepril for 5 years.
Results
HCTZ/benazepril
(n = 5,762)
Amlodipine/benazepril
(n = 5,744)
Amlodipine/benazepril better than
HCTZ/benazepril in reduction in BP and CV
endpoints
0
20
10
Primary endpoint
11.8
9.6
%
(p < 0.001)
Jamerson K, et al. N Engl J Med 2008;359:2417-28
0
10
20
%
(p = 0.04)
Myocardial infarction
2.8 2.2

8. Incident Diabetes in Clinical Trials of
Antihypertensive Drugs
Odds ratio of incident diabetes Incoherence=0.000017
ARB
ACE Inhibitor
CCB
Placebo
β blocker
Diuretic Referent
0.90 (0.75-1.09) p=0.30
0.77 (0.63-0.94) p=0.009
0.75 (0.62-0.90) p=0.002
0.67 (0.56-0.80) p<0.0001
0.57 (0.46-0.72) p<0.0001
0.50 0.70 0.90 1.26
Elliott WJ, Meyer PM. Lancet. 2007;369:201–207.

9. Potential Adverse Effects of
Thiazide Diuretics
• Increase Triglycerides
• Reduce HDL-cholesterol
• Worsen insulin sensitivity
• Augment renin-angiotensin system
• Increase aldosterone (sodium retention)
9

10. GEMINI: Hemoglobin A1c
P=0.65
P<0.0001
MeanHbA1c(%)
Carvedilol
(n=454)
Metoprolol tartrate
(n=657)
Treatment Difference
Carvedilol vs
Metoprolol tartrate
-0.13% (-0.22, -0.04)
P=0.004
1111 patients
Bakris G et al. JAMA. 2004;292:2227-2236.
Baseline Month 5 Baseline Month 5
7.0
7.1
7.2
7.3
7.4
7.5

11. HOPE Study
• The Heart Outcomes Prevention Evaluation (HOPE) Study:
Multicenter, randomized trial, 9,297 patients 55 years old,
history of cardiovascular disease, or diabetes plus at least
one other CVD risk factor
• Ramipril v placebo for an average of 4.5 years
• Combined primary endpoint - myocardial infarction, stroke,
or cardiovascular death
• Results – Mean reduction in blood pressure was small =
3/2mmHg (only account for 25-40% of observed risk
reduction)
Yusuf S, et al. N Engl J Med. 2000;342:145-153.

12. HOPE Study Outcomes:
Events Per Patient Group
0
5
10
15
20
Placebo Ramipril
Combined
Primary
Outcome*
Cardio-
vascular
Death
Myocardial
Infarction
Stroke Non-Cardiovascular
Death
Total
Mortality
Yusuf S, et al. N Engl J Med. 2000;342:145-153.
RR=22%
P<0.001
RR=26%
P<0.001
RR=20%
P<0.001
RR=32%
P<0.001
RR=16%
P=0.005
RR=0%
P=NS
RR=Relative risk reduction
*The occurrence of myocardial infarction, stroke or cardiovascular death

13. Left Ventricular Hypertrophy
LVH is an independent predictor of myocardial
infarction and sudden cardiac death. LVH can lead
to both systolic and diastolic heart failure.

14. Losartan Intervention for Endpoint Reduction
in Hypertension Study (LIFE)
• LIFE Study overview
• Double-blind, randomized trial to compare the effects
of losartan and atenolol on cardiovascular morbidity
and mortality in high-risk patients with hypertension
and left ventricular hypertrophy (LVH)
• Population
• 9,193 patients (55 to 80-years-old)
• Previously treated or untreated essential hypertension
(systolic BP 160–200 or diastolic BP 95–115 mmHg)
• ECG LVH
• 1,195 patients (13%) had diabetes at baseline
Dahlof B, et al. Lancet. 2002;359:995-1003.

15. LIFE: Primary Composite Endpoint
0 6 12 18 24 30 36 42 48 54 60 66
Dahlof B, et al. Lancet. 2002;359:995-1003.
Study month
Proportionofpatients
withfirstevent(%)
Intention-to-treat
Losartan
Atenolol
2
4
6
8
10
12
14
16
Adjusted risk reduction 13·0%, P=0·021
Unadjusted risk reduction 14·6%, P=0·009

16. CLEVER Trial
• A Randomized, Double-Blind, Multicenter Study
Comparing the Effects of Carvedilol Modified-
Release Formulation (carvedilol CR) and Atenolol
in Combination with and Compared to an
AngiotensinConverting Enzyme Inhibitor
(lisinopril) on LEft VEntricular Mass Regression in
Hypertensive Subjects with Left Ventricular
Hypertrophy (LVH)
Miller A, et al. Presented at the 24th Annual Meeting of the American Society of Hypertension; May 6-9,
2009; San Francisco, CA. Abstract LB-OR-08.

17. PRIMARY ENDPOINT: Change from Baseline in LVM Indexed by
BSA (g/m2) MRI at Month 12
-7.9 (-9.6, -6.3)* -6.7 (-8.2, -5.1)* -6.3 (-8.0, -4.7)*
N=59 N=76 N=60
Lis + Lis Aten + Lis CR + Lis
 Carvedilol CR vs. Atenolol Mean (95%CI), p-value
0.3 (-1.8, 2.5), 0.76
 Carvedilol CR vs. Lisinopril Mean (95%CI), p-value 1.6 (-0.7, 3.9), 0.17
gm/M2
Miller A, et al. Presented at the 24th Annual Meeting of the American Society of Hypertension; May 6-9,
2009; San Francisco, CA. Abstract LB-OR-08.
0
80

18. • New BP goal <130/80 for high risk individuals
• Patients with ASCVD
• 10% ten-year risk by pooled cohort equation
• Lifestyle Modification plus antihypertensive agents from
4-classes:
• ACE inhibitors, Angiotensin receptor blockers (ARBs),
calcium channel blockers, long acting thiazides
• Beta blockers only for compelling indications – avoid
use of atenolol
Summary: 2017
ACC/AHA Hypertension Guidelines