Hypertension Management

Hypertension is defined as systolic blood pressure (SBP) of 140 mmHg or greater, diastolic blood pressure (DBP) of 90 mmHg or greater, or taking antihypertensive medication. VI JNC, 1997 Types of hypertension  Essential hypertension   90% No underlying cause  Secondary hypertension  Underlying cause Causes of Secondary Hypertension  Renal    Parenchymal Vascular Others     Endocrine Neurogenic Miscellaneous Unknown Hypertension: Predisposing factors       Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet Co-existing disorders such as diabetes, obesity and hyperlipidaemia  High intake of alcohol  Sedentary life style 1999 WHO-ISH Guidelines : Definitions and Classifications of BP Levels SBP (mm Hg) < 120 < 130 130-139 140-159 140-149 160-179 > 180 > 140 140-149 DBP (mm Hg) < 80 < 85 85-89 90-99 90-94 100-109 > 110 < 90 < 90 Category* Optimal Normal High-normal Grade 1 hypertension (mild) Borderline subgroup Grade 2 hypertension (moderate) Grade 3 hypertension (severe) ISH Borderline subgroup WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17:151 1999 WHO-ISH Guidelines: Stratification of risk to Quantify Prognosis Degree of hypertension (mm Hg) Grade 1-mild Grade 2-moderate Grade3-severe (SBP 140-159 (SBP 160-179 (SBP > 180 or DBP 90-99) or DBP 100-109) or DBP > 110) Low risk Med risk High risk Med risk High risk Med risk high risk Very high risk Very high risk Risk factors and disease history I No other risk factors II 1-2 risk factors III > 3 risk factors or target organ disease or diabetes IV Associated Clinical conditions Very high risk Very high risk Very high risk WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151 Diseases Attributable to Hypertension Gangrene of the Lower Extremities Aortic Aneurym Heart Failure Left Ventricular Hypertrophy Myocardial Infarction Hypertensive Encephalopathy HYPERTENSION Coronary Heart Disease Chronic Kidney Failure Stroke Cerebral Preeclampsia/ Hemorrhage Eclampsia Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935 Blindness 1999 WHO-ISH Guidelines: Desirable BP Treatment Goals  Optimal or normal BP (< 130/85 mm Hg) for  Young patients  Middle-age patients  Diabetic patients  High-normal BP (< 140/90 mm Hg) desirable for elderly patients  Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is  < 1 g/d - 130/80 mm Hg  > 1 g/d - 125/75 mm Hg Significant benefits from intensive BP reduction in diabetic patients Major CV events / 100 patient-yr 30 25 20 15 10 5 0 < 90 mm Hg < 85 mm Hg < 80 mm Hg (target DBP) Lancet 1998, 351, 1755 24.4 18.6 11.9 Relative risks of specific types of clinical complications related to tight and less tight BP Control Patients with aggregate and points Tight Less tight control control (n=758) (n=390) 259 170 82 134 107 38 8 68 62 83 69 34 8 54 Absolute risk (events/1000 patients-yr) Less Tight tight control control 50.9 67.4 13.7 22.4 18.6 6.5 1.4 12.0 20.3 27.2 23.5 11.6 2.7 19.2 Clinical end point Any diabetes-related end point Deaths related to diabetes All cause mortality Myocardial infarction Stroke Peripheral vascular disease Microvascular disease p 0.0046 0.019 0.17 0.13 0.013 0.17 0.0092 RR for tight control (95% Cl) 0.76 (0.62-0.92) 0.68 (0.49-0.94) 0.82 (0.63-1.08) 0.79 (0.59-1.07) 0.56 (0.35-0.89) 0.51 (0.19-1.37) 063 (0.44-0.89) Ref : UK Prospective Diabetes Study Group BMJ 1998; 317:703 Life style modifications  Lose weight, if overweight  Limit alcohol intake  Increase physical activity  Reduce salt intake  Stop smoking  Limit intake of foods rich in fats and cholesterol Factors affecting choice of antihypertensive drug  The cardiovascular risk profile of the patient  Coexisting disorders  Target organ damage  Interactions with other drugs used for concomitant conditions  Tolerability of the drug  Cost of the drug Drug therapy for hypertension Class of drug Diuretics -blockers Calcium channel blockers Example Hydrochlorothiazide Atenolol Amlodipine Initiating dose 12.5 mg o.d. 25-50 mg o.d. 2.5-5 mg o.d. Usual maintenance dose 12.5-25 mg o.d. 50-100 mg o.d. 5-10 mg o.d. -blockers ACE- inhibitors Angiotensin-II receptor blockers Doxazosin Lisinopril Losartan 1 mg o.d. 2.5-5 mg o.d. 25-50 mg o.d. 1-8 mg o.d. 5-20 mg o.d. 50-100 mg o.d. Diuretics Example: Hydrochlorothiazide  Act by decreasing blood volume and cardiac output  Decrease peripheral resistance during chronic therapy  Drugs of choice in elderly hypertensives Drawbacks  Hypokalaemia  Hyponatraemia  Hyperlipidaemia  Hyperuricaemia (hence contraindicated in gout)  Hyperglycaemia (hence not safe in diabetes)  Not safe in renal and hepatic insufficiency Beta blockers Example: Atenolol  Block 1 receptors on the heart  Block 2 receptors on kidney and inhibit release of renin  Decrease rate and force of contraction and thus reduce cardiac output  Drugs of choice in patients with co-existent coronary heart disease Drawbacks  Adverse effects: lethargy, impotency, bradycardia  Not safe in patients with co-existing asthma and diabetes  Have an adverse effect on the lipid profile Calcium channel blockers Example: Amlodipine  Block entry of calcium through calcium channels  Cause vasodilation and reduce peripheral resistance  Drugs of choice in elderly hypertensives and those with co-existing asthma  Neutral effect on glucose and lipid levels Drawbacks  Adverse effects: Flushing, headache, Pedal edema ACE inhibitors Example: Lisinopril, Enalapril  Inhibit ACE and formation of angiotensin II and block its effects  Drugs of choice in co-existent diabetes mellitus Drawbacks  Adverse effect: dry cough, hypotension, angioedema Angiotensin II receptor blockers Example: Losartan  Block the angiotensin II receptor and inhibit effects of angiotensin II  Drugs of choice in patients with co-existing diabetes mellitus Drawbacks  Adverse effect: dry cough, hypotension, angioedema Alpha blockers Example: Doxazosin  Block -1 receptors and cause vasodilation  Reduce peripheral resistance and venous return  Exert beneficial effects on lipids and insulin sensitivity  Drugs of choice in patients with co-existing hyperlipidaemia, diabetes mellitus and BPH Drawbacks  Adverse effects: Postural hypotension Antihypertensive therapy: Side-effects and Contraindications Class of drugs Diuretics (e.g. Hydrochlorothiazide) Main side-effects Contraindications/ Special Precautions Electrolyte imbalance, Hypersensitivity, Anuria total and LDL cholesterol levels, HDL cholesterol levels,  glucose levels,  uric acid levels Impotence, Bradycardia, Fatigue Hypersensitivity, Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure -blockers (e.g. Atenolol) Antihypertensive therapy: Side-effects and Contraindications (Contd.) Class of drug Calcium channel blockers (e.g. Amlodipine, Diltiazem) Main side-effects Pedal edema, Headache Contraindications/ Special Precautions Non-dihydropyridine CCBs (e.g diltiazem)– Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction. Dihydropyridine CCBs– Hypersensitivity Hypersensitivity -blockers (e.g. Doxazosin) Postural hypotension ACE-inhibitors (e.g. Lisinopril) Angiotensin-II receptor blockers (e.g. Losartan) Cough, Hypertension, Angioneurotic edema Headache, Dizziness Hypersensitivity, Pregnancy, Bilateral renal artery stenosis Hypersensitivity, Pregnancy, Bilateral renal artery stenosis Choosing the right antihypertensive Condition Asthma Preferred drugs Calcium channel blockers -blockers/ACE inhibitors/ Angiotensin-II receptor blockers -blockers Other drugs that can be used -blockers/Angiotensin-II receptor blockers/Diuretics/ ACE-inhibitors Calcium channel blockers Drugs to be avoided -blockers Diabetes mellitus Diuretics/ -blockers -blockers/ Diuretics High cholesterol levels Elderly patients (above 60 years) BPH ACE inhibitors/ Angiotensin-II receptor blockers/ Calcium channel blockers -blockers/ACEinhibitors/Angiotensin-II receptor blockers/- blockers -blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers Calcium channel blockers/Diuretics -blockers Limitations on use of antihypertensives in patients with coexisting disorders Coexisting Disorder Diabetes Dyslipidaemia CHD Diuretic Caution/x x  -blocker Caution/x x  ACE All inhibitor antagonist    CCB    1-blocker       Heart failure Asthma/COPD Peripheral vascular disease Renal artery stenosis    3/Caution x Caution   /Caution Caution   Caution Caution        x x   Effect of various antihypertensives on coexisting disorders Total LDLHDLSerum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity Diuretic       -blockers ACE inhibitors All antagonists CCBs -      -   - - - - - - - - - -blockers       Combination therapy for hypertension – Recommended by JNC-VI guidelines and 1999 WHO-ISH guidelines With any single drug, not more than 25–50% of hypertensives achieve adequate blood pressure control J Hum. Hypertens 1995; 9:S33–S36 For patients not responding adequately to low doses of monotherapy Increase the dose of drug. This, however, may lead to increased side effects Substitute with another drug from a different class Add a second drug from a different class (Combination therapy) If inadequate response obtained Add second drug from different class (Combination therapy) Advantages of fixed-dose combination therapy  Better blood pressure control  Lesser incidence of individual drug’s side-effects  Neutralisation of side-effects  Increased patient compliance  Lesser cost of therapy Fixed-dose combinations as recommended by JNC-VI (1997) guidelines and 1999 WHO-ISH guidelines  Calcium channel blocker and -blocker (e.g. Amlodipine and Atenolol)  Calcium channel blocker and ACE-inhibitor (e.g. Amlodipine and Lisinopril)  ACE-inhibitor and Diuretic (e.g. Lisinopril and Hydrochlorothiazide)  -blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide) Efficacy and Tolerability of a fixed-dose combination of amlodipine and atenolol (Amlopres-AT) in Indian Hypertensives (n=369) Reduces BP effectively Blood Pressure (mm Hg) 200 90 80 80.5% 100 50 0 143.8 + 13.2 % responders 150 175.4+ 19.4 70 60 50 40 30 20 106.8 + 10.5 88.2 + 7.6 Systolic Diastolic 10 0 Basal Week 4 Safe and well tolerated  Adverse events were reported in 7.9% of patients  Common side effects included edema, fatigue and headache Indian Practitioner 1997; 50: 683-688. Efficacy and Tolerability of combined amlodipine and lisinopril (Amlopres-L) in Indian hypertensives (n=330) Reduces BP effectively Blood Pressure (mm Hg) 200 150 100 50 0 90 143.8 + 13.2 % responders 175.4+ 19.4 106.8 + 10.5 80 70 60 50 40 30 20 77.65 88.2 + 7.6 Systolic Diastolic 10 0 Basal Week 4 Safe and well tolerated  Adverse events were reported in 9.7% of patients  Side effects commonly reported included cough and edema  Only 1.76% of patients withdrew from the study. Indian Practitioner 1998; 51: 441-447. Drugs in special conditions Condition  Pregnancy  Preferred Drugs Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin Beta-blockers, ACE inhibitors, Calcium channel blockers ACE inhibitors, beta-blockers 1999 WHO-ISH guidelines  Coronary heart disease   Congestive heart failure  Summary  Hypertension is a major cause of morbidity and mortality, and needs to be treated  It is an extremely common condition; however it is still underdiagnosed and undertreated  Hypertension is not controlled with monotherapy in at least 50% of patients; in these patients combination therapy is required