CUANDO COMENZAR, HASTA CUANTO LLEGAR Y CON QUE TRATAR AL

PACIENTE HIPERTENSO CON DM2

Patricio López-Jaramillo MD PhD FACP

Director de Investigaciones y de la Clínica de Síndrome Metabólico, Prediabetes y Diabetes, FOSCAL

Director de Investigaciones de la Facultad de Medicina UDES

Presidente de la Sociedad Latinoamericana de Hipertension (LASH) 2014-2016

Bucaramanga-Colombia

RRR OF COMBINATION AND EACH INTERVENTION VS DOUBLE PLACEBO

Overall

RR

R

0%

10%

20%

30%

40%

50%

28% 26%

6%

Combo Rosuva

Only Cand + HCTZ

Only

34

Co-Primary 2

RR

R

0%

10%

20%

30%

40%

50%

40%

20% 24%

Combo Rosuva

Only

Cand+HCTZ

Only

Highest Third of SBP

0%

10%

20%

30%

40%

50%

19%

31%

-8%

Combo Rosuva Only

Cand + HCTZ Only

Lower Two Thirds of SBP

Initiation of Antihypertensive Treatment Grade 2 and 3 Hypertension

The body of evidence in favor of antihypertensive treatment

provided by randomized controlled trials was obtained in

hypertensive patients whose baseline SBP was ≥160 mm Hg, who

could presently be classified as grade 2 or 3 hypertensives. Some

recent trials included patients with lower SBP values at

randomization, but these patients already were under background

antihypertensive treatment at the time of randomizationand could

likely be classified at least as grade 2 hypertensives. Therefore,

the large reduction of fatal and nonfatal cardiovascular events

induced by BP lowering in these trials and their meta-analyses

provides the strong recommendation that all individuals with BP in

grade 2 or 3 hypertension range be treated with drugs

In all patients, drug treatment should be accompanied by lifestyle

measures, and in grade 2 hypertensives, lifestyle measures can be

used alone for a few weeks to test their effectiveness and the need

for addition of drugs.

The constancy of the relative risk reduction

throughout the hypertension grades shown by the

HOPE 3 study and a recent meta-analysis favors

the conclusion that all grades of hypertension

benefit from BP lowering and provides a stronger

support to the recommendation to initiate drug

treatment in grade 1 low-to-moderate risk

hypertensives than the arguments that could be

used in the 2013 LASH guidelines.

It is thought that this recommendation could be

given now a higher level, such as Class I, Level A

or B.

Grade 1 Hypertension

The very recent results of the Heart Outcomes Prevention

Evaluation (HOPE)-3 trial support that antihypertensive

treatment in patients at intermediate risk without previous

cardiovascular events and high normal blood pressure is not

associated with a reduction of major cardiovascular events

compared with placebo. Only in patients with a basal SBP higher

than 143.5 mm Hg (mean 154 mm Hg) a benefit in reducing the

primary outcomes was observed.

Therefore, at present, no evidence is available suggesting

initiation of antihypertensive drug treatment in high normal blood

pressure individuals. When other risk factors are present in

these subjects, as often occurs, lifestyle measures or

pharmacological treatment of these risk factors (such as

cholesterol or blood glucose–lowering drugs) are likely to be

more definitely beneficial.

High Normal Blood Pressure

Blood Pressure Treatment Targets

The Lower the Better Versus the J-Shaped

Curve Hypothesis The Latin America consensus on hypertension in patients with type 2 diabetes

mellitus and metabolic syndrome recommended a SBP target of less than 140

mm Hg as in nondiabetic hypertensive individuals.

The overall reductions in stroke and all vascular events were related to the

degree of BP lowering achieved in the range between 140 and 130 mm Hg,

but in no one of these studies was the average achieved BP <130 mm Hg.

The results of SPRINT and another recent trial have been included in an

updated meta-analysis of all 35 trials of BP lowering (138 452 individuals) that

could be stratified according to the usual cutoffs of achieved SBP. Lowering

SBP below 130 mm Hg was found to reduce relative risk of major

cardiovascular outcomes, but the absolute cardiovascular risk reduction was

definitely smaller, and the risk of permanent treatment discontinuations for

adverse events significantly greater than in the trials in which SBP was

lowered across the cutoff of 140 mm Hg.

LASH Guidelines: A useful tool for our region

En la mayoria de patientes hipertensos con diabetes

tipo 2 el blanco de PA no es alcanzado con

monoterapia y se debe incluir dos o mas agentes

hipotensores. Si antes del inico del tratamiento la PA

esta muy elevada, es recomendado iniciar con una

combinacion de dos drogas. Una combinacion de dosis

fija de un IECA o ARA con CCB o un diuretico son

recomendados

Diurético

s

IECA

Antagonistas

del Calcio

ARA II -bloqueantes

Otros

Combinaciones de antihipertensivos

Efecto antihipertensivo

Protección cardiovascular

Optima tolerabilidad

Recomendaciones de las Guías LASH 2013

Preferentes

Utiles

Posibles

No recomendadas

Years of Follow-up

Proportio

n w

ith events

0.0

0.1

0.2

0.3

0.4

0 1 2 3 4 5 6 7

1st2nd3rd4th5th

# at Risk 1 2 3 4 5 6 7

1st

2nd

3rd

4th

5th

1627 1538 1451 1351 1252 1150 783 170

1627 1561 1497 1431 1365 1287 928 199

1627 1570 1528 1481 1414 1345 957 236

1624 1572 1515 1461 1411 1365 1016 247

1630 1583 1537 1495 1440 1389 1015 219

Log rank test P:

1st vs. 5th: <0.0001

2nd vs. 5th: <0.0001

3rd vs. 5th: 0.0466

4th vs. 5th: 0.9924

Males: Time to Adjudicated Primary Outcome 1 - CV Death MI Stroke

Years of Follow-up

Proportio

n w

ith events

0.0

0.1

0.2

0.3

0.4

0 1 2 3 4 5 6 7

1st

2nd

3rd

4th

5th

# at Risk 1 2 3 4 5 6 7

1st

2nd

3rd

4th

5th

875 836 791 736 703 658 426 75

877 849 830 797 763 716 477 95

876 850 832 811 787 767 505 87

876 858 842 827 810 790 528 93

877 862 849 841 830 815 554 108

Log rank test P:

1st vs. 5th: <0.0001

2nd vs. 5th: <0.0001

3rd vs. 5th: 0.0002

4th vs. 5th: 0.2990

Females: Time to Adjudicated Primary Outcome 1 - CV Death MI Stroke

HAZARD RATIOS: MEN AND WOMEN

Adj HR (95%CI) P Events

Per 1 Kg Increase N (%) Rate

Composite 0.91 (0.90, 0.93) <0.001 1471 (18.1) 3.2

CV Death 0.88 (0.86, 0.90) <0.001 811 (10.0) 1.7

MI 0.97 (0.94, 1.00) 0.04 509 (6.3) 1.1

Stroke 0.90 (0.87, 0.93) <0.001 442 (5.4) 0.9

Revascularization 0.99 (0.97, 1.01) 0.16 1415 (17.4) 3.3

Heart Failure 0.89 (0.86, 0.91) <0.001 474 (5.8) 1.0

Death 0.87 (0.85, 0.88) <0.001 1347 (16.6) 2.8

Hazard Ratio

Reduced Risk

10.8

Increased Risk

Lopez-Jaramillo et al. Int J Cardiol 2014; 172; 458-461

Hazard Ratio

Reduced Risk

0.6 1.21

Increased Risk

Adj HR (95%CI) P Events

Per 1 Kg Increase N (%) Rate

Composite 0.76 (0.72, 0.80) <0.001 578 (13.2) 2.3

CV Death 0.70 (0.66, 0.75) <0.001 343 (7.8) 1.3

MI 0.79 (0.72, 0.86) <0.001 151 (3.4) 0.6

Stroke 0.84 (0.77, 0.90) <0.001 206 (4.7) 0.8

Revascularization 0.90 (0.85, 0.96) <0.001 349 (8.0) 1.4

Heart Failure 0.70 (0.64, 0.76) <0.001 176 (4.0) 0.7

Death 0.70 (0.67, 0.73) <0.001 566 (12.9) 2.2

FOSCAL/FOSCAL INTERNACIONAL investigaciones@foscal.com.co jplopezj@gmail.com

GRACIAS