BLOOD PRESSURE MANAGEMENT

Transcription

1 CV DISEASE PREVENTION IN DIABETES: WHAT WORKS AND WHAT DOES NOT BLOOD PRESSURE MANAGEMENT FELIPE MARTINEZ Professor of Medicina Cordoba National University Director. Instituto DAMIC-Fundacion Rusculleda CORDOBA- ARGENTINA

2 FELIPE MARTINEZ RESEARCH GRANTS,MEMBER OF STEERING COMEETEES, ADVISORY BOARDS AND/OR SPEAKER OF : ASTELLAS,ASTRA ZENECA, AVENTIS, BOHERINGER INGELHEIM, BRISTOL MAYER SQUIBB, ELEA, GLAXO, MERCK, MERCK SHARP & DHOME, MYOGEN, NOVARTIS, PFIZER, SERVIER, TAKEDA.

3 FIRST WHY?

4 WHO s World Health Statistics 2012 report, which includes data from 194 countries, states that one in three adults worldwide has raised blood pressure and one in 10 suffers from diabetes.

5 POSITION STATEMENT OF ADA AND EASD (DIABETES CARE, 35: JUNE 2012) The increasing incidence of diabetes and hypertensión is almost parallel to the association of both diseases

6 SECOND WHAT WORKS?

7 ESC/EASD joint guidelines on diabetes and cardiovascular diseases European Heart journal (2007) 28,88-136

8 Blood pressure: recommendations EASD/ADA Joint Guidelines 1)Pts DBT and HP: BP < 130/80 2)CV risk in DBT is increased and can be reduced lowering BP 3)Usually requires a combination of several antihypertensive drugs 4)Should be prescribed a RAS inhib. 5)Screening of microalbuminuria and the use of ACEI and ARBs, improves morbidity in DBT B 1 A 1 A 1 A 1 A

9 FIVE YEARS LATER ADA 2012

10 Recommendations: Hypertension/Blood Pressure Control Treatment (1) Patients with a systolic blood pressure mmhg or a diastolic blood pressure mmhg (E) May be given lifestyle therapy alone for a maximum of 3 months If targets are not achieved, patients should be treated with the addition of pharmacological agents ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S29.

11 Recommendations: Hypertension/Blood Pressure Control Treatment (2) Patients with more severe hypertension (systolic blood pressure 140 mmhg or diastolic blood pressure 90 mmhg) at diagnosis or follow-up (A) Should receive pharmacologic therapy in addition to lifestyle therapy ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S29.

12 Recommendations: Hypertension/Blood Pressure Control Treatment (4) Pharmacologic therapy for patients with diabetes and hypertension A regimen that includes either an ACE inhibitor or angiotensin II receptor blocker If one class is not tolerated, the other should be substituted Multiple drug therapy (two or more agents at maximal doses) is generally required to achieve blood pressure targets (B) ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S29.

13 Recommendations: Hypertension/Blood Pressure Control Treatment (5) If ACE inhibitors, ARBs, or diuretics are used, kidney function, serum potassium levels should be monitored (E) In pregnant patients with diabetes and chronic hypertension, blood pressure target goals of /65 79 mmhg are suggested in interest of long-term maternal health and minimizing impaired fetal growth; ACE inhibitors, ARBs, contraindicated during pregnancy (E) ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S29.

14 Pooled Recommendations: Main International Recent Guidelines ABCD, ALLHAT 1)ACEI- ASCOT, CAPP ARB HOT, INSIGHT LIFE, ONTARGET RENAAL SHAPE,SHEP SYST-EUR, STOP VALUE, UKPDS, ETC,ETC,ETC 2)Diuretic 3)CCB 4)BB ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S29.

15 ANGIOTENSINOGEN RENINE ANGIOTENSINE I ACE ANGIOTENSINE II AT II RECEPTOR ALDOSTERONE

16 VALUE MONOTERAPY RESULTS (Julius S, Weber M, Martinez F. : Hypertension. Sept 2006 ) Proportion of patients with first event (%) Time (months) Number at risk Valsartan Amlodipine 7 Valsartan 6 Amlodipine Myocardial infarction HR=1.041; 95% CI= ; p= Number at risk Valsartan Proportion of patients with first event (%) Amlodipine Valsartan Amlodipine Heart failure P=0.004 HR=0.630; 95% CI= ; p= Time (months) ANLO VALS Proportion of patients with first event (%) Time (months) Number at risk Valsartan Amlodipine Valsartan Amlodipine Stroke HR=1.070; 95% CI= ; p= Proportion of patients with first event (%) Time (months) Number at risk Valsartan Amlodipine Valsartan Amlodipine All-cause death HR=1.104; 95% CI= ; p= Figure 4. Secondary endpoints. Censored population.

17 VALUE MONOTERAPY RESULTS (Julius S, Weber M, Martinez F. : Hypertension. Sept 2006 ) DIABETIC PATIENTS PACIENTES DIABETICOS Months on monotherapy Heart failure Months on monotherapy Favors mejor VALS. valsartan Favors mejor amlodipine ACa Hazard ratio Myocardial infarction Favors mejorvals valsartan Favors mejor amlodipine ACa Hazard ratio Figure 6. Between group differences at various time points.

18 % LOWERING RAAS INHIBITION AND NEW ONSET DIABETES (JACC 7/2005) 50% 40% 30% 20% 10% 0% 33% 25% 24% 22% 16% 13% PL DI CA DI PL BB PL CA BB HOPE CAPP ALLHAT SOLVD LIFE CHARM ACEI ARB VALUE

19 THIRD WHAT DOES NOT?

20 1) FIRST GENERATION BB? 2) CENTRAL V.DILATORS? 3) PERIPHERAL V.DILATORS?

21 ANGIOTENSINOGEN RENINE ANGIOTENSINE I ACE ANGIOTENSINE II AT II RECEPTOR ALDOSTERONE

22

23 FORTH WHAT COULD WORK?

24 ONE Chronobiology impact

25 Influence of time of day of blood pressure lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes Hermida CH et al Diabetes Care 34: ,2011

26 CV OUTCOMES AS FUNCTION OF TIME OF DAY TREATMENT OF HT IN TYPE 2 DIABETIC PATIENS Diabetes Care 34: ,2011 TOTAL EVENTS TOTAL DEATHS CEREBROV. EVENTS AMI HEART FAILURE , Bedtime better Awaiking better

27 POSITION STATEMENT OF ADA AND EASD (DIABETES CARE, 35: JUNE 2012) Pharmacogenomics and chronotherapy may very well inform treatment decisions in the future

28 TWO Aditional RAAS inhibition

29 FUTURE INTERVENTIONS IN RAAS 1)Cardioselective Inhibition of MCR 2)Pure dual inhibitors. 3)Antioxidantes / NO donnors ARBs 4)Specific cardiorenal inhibitors

30 ANGIOTENSINOGEN RENINE ANGIOTENSINE I ACE ANGIOTENSINE II AT II RECEPTOR ALDOSTERONE

31

32 Aldosterone antagonists, blockers, inhibitors? Aldosterone Cortisol Aldo Synthase Inhibitors LCI ASI MSDxx MR AT MRA MR antagonists Steroidal Spironolactone Potassium canrenone Eplerenone Non steroidal

33 ALDOSTERONE INHIBITION AND CARDIOVASCULAR PROTECTION: MORE IMPORTANT THAN IT ONCE APPEARED Martinez F. Cardiovascular Drugs and Therapy: 24-4 (2010), Page 345 There is consistent evidence of the beneficial effects of aldo blockade in hypertension Extending the therapeutic effect, there are small scale studies that suggest aditional benefits in diabetic patients

34 NIH (National Institute of Health) TOPCAT Treatment Of Preserved Cardiac function heart failure with an Aldosterone antagonist

35 TOPCAT PTS HF with EF > 45% PRIMARY ENDPOINT: TOTAL AND CV Mortalty SECONDARY ENDPOINTS: INCIDENCE OF DIABETES AF

36 Aldosterone antagonists, blockers, inhibitors? Aldosterone Cortisol Aldo Synthase Inhibitors LCI ASI MSDxx MR AT MR antagonists Steroidal MRA Spironolactone Potassium canrenone Eplerenone Non steroidal

37 FUTURE INTERVENTIONS IN RAAS 1)Cardioselective Inhibition of MCR 2)Pure dual inhibitors. 3)Antioxidantes / NO donnors ARBs 4)Specific cardiorenal inhibitors

38 DIFERENT DUAL INHIBITION OMAPATRILAT ACE NEP LCZ696 AT II AT II REC

39 Angiotensine Receptor Neprelisine Inhibitor

40 Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebocontrolled, active comparator study. Luis Miguel Ruilope, Andrej Dukat, Michael Böhm, Yves Lacourcière, Jianjian Gong The Lancet, 16 de marzo de 2010.

41 FUTURE INTERVENTIONS IN RAAS 1)Cardioselective Inhibition of MCR 2)Pure dual inhibitors. 3)Antioxidants / NO donnors ARBs 4)Specific cardiorenal inhibitors

42

43 THREE Pharmacologic prevention

44 TROPHY DEVELOPMENT OF NEW HYPERTENSION p p JULIUS S. ACC 03/06- NEJM 03/06

45 HEALTHY PEOPLE 2020 US Dept of Health and Human Services. Healthy People 2020 topics and objectives. Nov 30, WHO 2012 Objectives in Diabetes 1) Reduce incidence 2) Reduce CV risk 3) Improve glycemic control 4) Reduce economic burden

46 THE ABCD OF DRUG TREATMENT IN DIABETES A = ANTIPLATELET B = BLOOD PRESSURE C = CHOLESTEROL D = DIABETES CONTROL American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2010

47 The problem of adherence to treatment HYPERTENSION DIABETES Manhattan Research 2004

48 % adherence to treatment Improving adherence with a FDC (2 components) in hypertensive patients % % N= year N= year N= year N= year N= year 2 SEPAR. DRUGS FDC 1.- Meta-analysis; Bengalore 2007; 2.- Dickson et al 2008

49 THEN A POLYPILL IS JUSTIFIED IN DIABETIC/HYPER TENSIVES PTS?

50 The FOCUS Project: Improving Equitable Access and Adherence to Secondary Cardiovascular Prevention with a Fixed- Dose Combination Drug. Study Design and Objectives G. Sanz, MD PhD (a), V. Fuster MD PhD(a, b), L. Guzmán MD (c), A. Guglietta, MD PhD (d), J.A. Arnáiz MD PhD(e), F. Martínez, MD PhD (f), A. Sarria MD PhD, (g), M.C. Roncaglioni, Biol Sci Dr (h), K, Taubert PhD (i) on behalf of FOCUS investigators* AHJ 2011

51 FOCUS: ORGANIZATION GENERAL COORDINATION CNIC MADRID, SPAIN CHAIRMAN: VALENTIN FUSTER EUROPE S. AMERICA 40 SITES 2000 PATIENTS COORDINATION: ITALY: M. NEGRI FOUND. SPAIN: CARLOS III INST. 40 SITES 2000 PATIENTS HYPERTENSION % COORDINATION: DAMIC / RUSCULLEDA FD ARGENTINA, BRASIL AND PARAGUAY DIABETES %

52 POLYPILL ASPIRIN RAMIPRIL SIMVASTAT.

53 BUT OBVIOUSLY

54 THE EARLIER THE BETTER

55 CV DISEASE PREVENTION IN DIABETES: WHAT WORKS AND WHAT DOES NOT CONCLUSIONS FELIPE MARTINEZ Professor of Medicina Cordoba National University Director. Instituto DAMIC-Fundacion Rusculleda CORDOBA- ARGENTINA

56 BP MANAGEMENT IN DIABETICS 1) ACEIs and ARBs ARE FIRST LINE DRUGS IN THE MAJORITY OF PTS 2) DIURETICS MAY BE ASSOCIATED 3) CCB AND NEW BB ARE USSUALLY OPTIONS AS SECOND AND THIRD DRUGS 4) NEW INTERVENTIONS AS ALDO BLOCKERS AND ARNI, SHOW OPTIMISTIC EVIDENCE 5) OTHER DRUGS NEED MORE STUDIES

57 MANY THANKS