1. BY Dr. Khaled Helmy Al Mahmora Chest Hospital BY Dr. Khaled Helmy Al Mahmora Chest Hospital Treatment Of Hypertension In Diabetes

2. Hypertension & Diabetes Hypertension & Diabetes

3.  Hypertension affecting 20–60% of patients with diabetes.  In type 2 diabetes, hypertension is often present as part of the metabolic syndrome while in type 1 diabetes, hypertension may reflect the onset of diabetic nephropathy.  Hypertension substantially increases the risk of both macrovascular and microvascular complications.  Hypertensive diabetic patients are also at increased risk for diabetes-specific complications including retinopathy and nephropathy.  In recent years, adequate data from well-designed randomized clinical trials have demonstrated the effectiveness of aggressive treatment of hypertension in reducing both types of diabetes complications. Hypertension Diabetes

4.  Diabetes increases the risk of coronary events twofold in men and fourfold in women after menopause.  People with both diabetes and hypertension have approximately twice the risk of cardiovascular disease as non-diabetic people with hypertension  In the U.K. Prospective Diabetes Study (UKPDS) epidemiological study, each 10-mmHg decrease in mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes, 15% for deaths related to diabetes, 11% for myocardial infarction, and 13% for microvascular complications. Hypertension Diabetes

5. Normotensive Hypertension In recent years, adequate data from well-designed randomized clinical trials have demonstrated that structural changes in vessels start 5 years before BP elevated. patients who still have normal BP but have the high risk to develop high Bp(Patient at risk) are classified as normotensive hypertension and of course one of them is diabetic patients and they should be managed as soon as possible.

6. Strategy for management of Hypertensive Diabetic pts  Proper blood sugar control.  Achieve target level of BP control for diabetic patients  Early Detection of both diabetes and hypertension complications & manage them as well as delay their progression  Improve patients quality of life.

7. Target levels of blood pressure in patients with Diabetes Target levels of blood pressure in patients with Diabetes The UKPDS and the Hypertension Optimal Treatment (HOT) trial both demonstrated improved outcomes, especially in preventing stroke, in patients assigned to lower blood pressure targets. A target blood pressure goal of <130/80 mmHg is reasonable if it can be safely achieved <125/75 mmHg (in proteinuria >0.5-1g/d) It is very clear that many people will require more than one drug to achieve the recommended target.

8. Non-drug management of Hypertension Moderate sodium restriction,reduce salt intake from 200mmol (4600 mg) to 100mmol (2300 mg) daily  5 mm fall in DBP. Weight reduction (Loss of 1 kg weight  decrease mean arterial pressure of about 1 mm Hg. Moderately intense physical activity: 30-45 mins of brisk walking most days of the week has been shown to reduce BP. Stop smoking  decease micro, macrovasular Compilications Role of very low calorie diets ? Pharmacologic agents that induce weight loss?

9. Drug therapy of Hypertension in Diabetes Drug therapy of Hypertension in Diabetes There is strong evidence that pharmacological therapy of hypertension in patients with diabetes is effective in producing substantial decreases in cardiovascular and micro vascular diseases. It must be noted that many patients required more than one drug to achieve the specified target levels of blood pressure control. The UKPDS-Hypertension in Diabetes Study showed no significant difference in outcomes for treatment based on an ACE inhibitor compared with a ß-blocker.

10. Drug therapy of Hypertension in Diabetes,cont ACE inhibitors and ß-blockers appear to be superior to DCCBs therefore, DCCBs appear to be appropriate agents in addition to but not instead of ACE inhibitors, and ß-blockers. The UKPDS-Hypertension in Diabetes Study showed no significant difference in outcomes for treatment based on an ACE inhibitor compared with a ß-blocker. There are no long-term studies of the effect of ß -blockers, loop diuretics, or centrally acting adrenergic blockers on long-term complications of diabetes

11. A variety of trials have demonstrated that ACEIs / ARBs therapy should be considered the standard therapy to retard worsening albuminuria and subsequent renal disease. In Addition to their proper BP control, ACE inhibitors can retard the progression of microalbuminuria and can lower the percentage of patient who progress to end-stage renal disease and death. All patients with asymptomatic or symptomatic heart failure due to left ventricular systolic dysfunction should receive an ACE inhibitor. Approximately 50% of patients post-MI have significant left ventricular dysfunction and could benefits from ACE inhibitor therapy. Role of ACEIs & ARBs in Diabetes

12.  A meta-analysis of 20 published and two unpublished trials was carried out to determine whether ACE inhibitors could slow the progression of renal disease of varying degree showed that treatment of chronic renal insufficiency with ACE inhibitors delayed the progression of disease compared with placebo.  ACE inhibitors have a favorable effect on cardiovascular outcomes, this cardiovascular effect may be mediated by mechanisms other than blood pressure reduction. Role of ACEIs & ARBs in Diabetes, cont

13.  There are numerous studies documenting the effectiveness Of ACE inhibitors and ARBs in retarding the development and progression of diabetic complications :  EUCLID Study (Lisinopril vs placebo) Type1 Diabetic retinopathy  CALM study (Lisinopril vs Candestran & combination) BP & Microalbuminurea  RENAAL study(Losartan vs placebo) Type 1 Diabetic nephropathy  HOPE study (Ramiplil vs placebo) Reduction of MI,stroke,CV death All- cause death in high risk pts esp DM.  IDNT study (Irbesartan vs amlodipine vs placebo)  MARVAL study (Valsartan) Type 2 Diabetic nephropathy Irbesartan & Valsartan delay nephropathy amlodipine no better than placebo

14. ACEIs Vs ARBs

15. Angiotensinogen Other Substrates? Angiotensin I Angiotensin II Bradykinin & other substrates Psychological actionsActions? AT 2 AT 1 Renin ACE Renin Blockade ACE inhibitors Angiotensin II receptor antagonists blocking the Renin-Angiotensin system ? ACEIs Vs ARBs

16.  Evidence for beneficial outcomes (especially renal) with ARBs is growing but varying opinion on their optimal role.  Unfortunately, several ARB outcome trials have avoided a head-to-head comparison with ACEIs.  Losartan was not superior to captopril in patients with heart failure ( ELITE II), captopril reduced CV-death in post-MI patients more than losartan( OPTIMAAL ) However, both of these studies found that less patients discontinued losartan due to adverse effects  ARBs are an alternative in patients who develop ACEI induced cough but are more expensive than most ACEIs  ACEI-ARB combinations show some promise for renal outcomes ( CALM, COOPERATE), however they are expensive.

17. Approach to Combination Therapy The ABCD Approach A = ACEI or ARB B =  -blocker C = CCB D = diuretic low-dose  If initial drug is A or B  adding drug C or D provides a synergistic effect.  If initial drug is C or D  adding drug A or B provides a synergistic effect; (C+diuretic, also option). Verapamil or diltiazem with a β-blocker negative effects on heart (e.g. ↓ heart rate and ↓ cardiac output) CCBS and α-blockers potential for excessive hypotension; increased risk of falls, etc.

18. Thiazide like diuretic (low dose→HCT 12.5-25mg od) B blocker (cardioselective-e.g. atenolol, metoprolol) Long acting calcium channel blockers (amlodipine) 1 st potion ACEIs Monotherapy Drug therapy in Hypertension with Diabetes Drug therapy in Hypertension with Diabetes 2 nd option ARBs OR + Combination

19. Summary  Non-pharmacological measures (particularlyweight loss and reduction in salt intake) should be encouraged in all patients with diabetes, independently of the existing blood pressure.  The goal blood pressure to aim at during behavioural or pharmacological therapy is below 130/80 mmHg.  To reach this goal, most often combination therapy will be required.  It is recommended that all effective and well tolerated antihypertensive agents are used, generally in combination.

20.  In diabetic patients with high blood pressure, who may sometimes achieve blood pressure goal by monotherapy, the first drug to be tested should be a blocker of the renin–angiotensinsystem (ACE & ARBS)  The finding of microalbuminuria in type 1 or 2 diabetics is an indication for antihypertensive treatment, especially by a blocker of the renin–angiotensin system, irrespective of the blood pressure values(normotesive Hypertension). Summary, cont

21. DCCBs (compared with ACE inhibitors, ARBs, ß-blockers, or diuretics) should be used as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. Other classes, including Alph -blockers, may be used under specific indications such as symptoms of BPH. Achievement of the target blood pressure goal with a regimen that does not produce burdensome side effects and is at reasonable cost to the patient is probably more important than the specific drug strategy. Summary, cont

22. Thank you Thank you