A Year in Hypertension Research

BHS Annual Meeting, Cambridge 14 th September 2011 Adrian J.B. Brady MD, FRCP(Glasg), FRCPE, FAHA Associate Professor, University of Glasgow Consultant Cardiologist Glasgow Royal Infirmary Glasgow, UK Secretary, British Hypertension Society Chairman, Guidelines Committee, British Cardiovascular Society European Society of Cardiology Guidelines Development Group

Disclosures: Research grants from: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Schering Plough, Roche, Servier

September 2010

•

Nurses join as full members of BHS

Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension: Results From the Double-Blind, Randomized, Placebo-Controlled Rheos Pivotal Trial

Baroreceptor Activation Therapy

Average 5.2 antihypertensive drugs

Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension : : Results From the Double-Blind, Randomized, Placebo-Controlled Rheos Pivotal Trial

Ter Arkh.

2011;83(4):52-5.

[Efficacy and safety of the first made in Russia alpha, beta long-acting adrenoblocker proxodolol in patients with arterial

hypertension

of the second degree].

[Article in Russian] Beliaeva SA .

Abstract AIM:

To study efficacy and safety of a new dose and dosage form of proxodolol--a beta adrenoblocker with alpha1-adrenoblocking activity--in patients with moderate arterial hypertension (AH).

MATERIAL AND METHODS:

A total of 60 patients with verified diagnosis of essential AH of the second degree were randomized into two groups: group 1 (n=40) received proxodolol, group 2 (n=20) was given carvedilol. The trial lasted for 89 days.

RESULTS:

The trial demonstrates that proxodolol is highly effective and safe in the treatment of AH.

CONCLUSION:

Proxodolol is effective and safe in hypertension, in a dose 120 mg its activity is the same as carvedilol in a dose 25 mg.

PMID: 21675275 [PubMed - indexed for MEDLINE]

BMJ. 2011; 342: d2234

BMJ. 2011; 342: d2234.

ARBs and the risk of MI

• • • What is already known on this topic

Angiotensin receptor blockers are important in the treatment of cardiovascular conditions Previous studies have shown an increased risk of myocardial infarction with these drugs and have raised concern among physicians and patients

• • • • What this study adds

There is firm evidence to refute the hypothesis of angiotensin receptor blockers increasing the risk of myocardial infarction (ruling out even a 0.3% absolute increase) Compared with controls (active treatment or placebo), angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes.

Despite lower blood pressure with angiotensin receptor blockers when compared with placebo, there also was no detectable beneficial effect for the outcome of myocardial infarction or cardiovascular mortality BMJ. 2011; 342: d2234

DALCETRAPIB CETP INHIBITOR TRIALS

• DAL-VESSEL, presented ESC Aug 2011 • DAL-PLAQUE, presented ESC Aug 2011

Ischemic Heart Disease Mortality Rate in Each Decade of Age vs Usual BP at the Start of that Decade 256 32 Age at Risk: 80-89 256 70-79 60-69 32 50-59 Age at Risk: 80-89 70-79 60-69 50-59 40-49 4 4 40-49 0 120 140 160 Usual SBP (mmHg) 180 Prospective Studies Collaboration, Lancet, v.360, Dec. 14, 2002 0 70 80 90 100 Usual DBP (mmHg) 110

Ischemic Heart Disease Mortality Rate in Each Decade of Age vs Usual BP at the Start of that Decade 256 32 Age at Risk: 80-89 256 70-79 60-69 32 50-59 Age at Risk: 80-89 70-79 60-69 50-59 40-49 4 4 40-49 0 120 140 160 Usual SBP (mmHg) 180 Prospective Studies Collaboration, Lancet, v.360, Dec. 14, 2002 0 70 80 90 100 Usual DBP (mmHg) 110

J-Curve HOT Study

1 0 3 2 10 9 5 4 8 7 6 < 80 Non-Ischemic Ischemic < 85 < 90 DBP (mmHg) CruickshankJM, Hannson L,CV Drugs Therapy 2000;14,373.

INVEST Trial Design

International trial in 22,576 patients with CAD and hypertension Randomized to multi-drug treatment strategies • verapamil SR + trandolapril + HCTZ • atenolol + HCTZ + trandolapril • Trandolapril recommended for all patients with diabetes Primary Outcome: First occurrence of all-cause mortality, nonfatal MI or nonfatal stroke Secondary Outcomes: All-cause mortality, nonfatal MI, nonfatal stroke, total MI and total stroke Main finding: risk for CV adverse outcomes was equivalent comparing the strategies Pepine et al. JAMA. 2003:290:2805-2816

INVEST Subanalysis: BP and Risk

DBP: Risk for Primary Outcome

50 Nadir = 84.1 mm Hg Primary Outcome Hazard Ratio 40 30 20 10 0 Total patients 176 2239 DBP (mm Hg) 11306 7376 1230 248

INVEST Subanalysis: BP and Risk

SBP/DBP: Risk for Primary Outcome

6 6 Nadir = 119.2

mm Hg Nadir = 84.1

mm Hg 4 4 2 2 0 105 115 125 135 145 155 165 SBP (mm Hg) 0 55 65 75 85 DBP (mm Hg) 95 105

INVEST Subanalysis: BP and Risk

DBP: Risk for All-Cause Death

50 40 Nadir = 85.8 mm Hg All-Cause Death Hazard Ratio 30 20 10 0 Total patients 176 2253 DBP (mm Hg) 11339 7367 1201 240 5 3 1

INVEST Subanalysis: BP and Risk

Stroke / MI and DBP Strata

20 MI Stroke 15 10 5 0 DBP (mm Hg)

V alsartan A ntihypertensive L ong-Term U se E valuation

15,313 randomised at 942 sites in 31 countries Average follow up 4.2 years Julius S et al. Lancet . June 2004;363.

BMJ 2011;342:d643 doi:10.1136/bmj.d643

BRADY AJB, ESC SEPT 2010

Conclusions • Different guidelines have many similarities • Blood pressure lowering is fundamental • Therapeutic drug choices are showing global concordance