Chronic hypertension medical therapy

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Hypertension Main page

Overview

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Classification

Primary Hypertension
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Hypertensive Urgency

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief: Lakshmi Gopalakrishnan, M.D.; Assistant Editor-In-Chief: Taylor Palmieri

Overview

There are many classes of medications for treating hypertension, together called antihypertensives, which by varying means act by lowering blood pressure. Evidence suggests that reduction of the blood pressure by 5-6 mmHg can decrease the risk of stroke by 40%, of coronary heart disease by 15-20%, and reduces the likelihood of dementia, heart failure, and mortality from vascular disease.

Medical Management

The aim of treatment should be blood pressure control to lower than 140/90 mmHg for most patients, and lower in certain contexts such as diabetes or kidney disease (some medical professionals recommend keeping levels below 120/80 mmHg).[2] Each added drug may reduce the systolic blood pressure by 5-10 mmHg, so often multiple drugs are necessary to achieve blood pressure control.

Commonly used drugs

Influence of age and race on medication efficacy

  • A randomized controlled trial by the Veterans Affairs Cooperative Study Group on Antihypertensive Agents reported the influence of patient age and race on the proportion of patients whose blood pressure was controlled by different agents.[2][3]
  • For example:
  • The effect of age and race are in part due to differences in plasma renin activity.[4][5]

Choice of initial medication

Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidelines.

Regarding cardiovascular outcomes, the ALLHAT study showed a slightly better outcome and cost-effectiveness for the thiazide diuretic chlortalidone compared to other anti-hypertensives in an ethnically mixed population.[6]

Whilst a subsequent smaller study (ANBP2) did not show this small difference in outcome and actually showed a slightly better outcome for ACE-inhibitors in older white male patients.[7]

Whilst thiazides are cheap, effective, and recommended as the best first-line drug for hypertension by many experts, they are not prescribed as often as some newer drugs. Arguably, this is because they are off-patent and thus rarely promoted by the drug industry.[8] Due to their metabolic impact (hypercholesterinemia, impairment of glucose tolerance, increased risk of developing Diabetes mellitus type 2), the use of thiazides as first line treatment for essential hypertension has been repeatedly questioned and strongly disencouraged.[9] [10] [11]

Physicians may start with non-thiazide antihypertensive medications if there is a compelling reason to do so. An example is the use of ACE-inhibitors in diabetic patients who have evidence of kidney disease, as they have been shown to both reduce blood pressure and slow the progression of diabetic nephropathy.[12] In patients with coronary artery disease or a history of a heart attack, beta blockers and ACE-inhibitors both lower blood pressure and protect heart muscle over a lifetime, leading to reduced mortality.

Advice in the United Kingdom

The risk of beta-blockers provoking type 2 diabetes led to their downgrading to fourth-line therapy in the United Kingdom in June 2006[13], in the revised national guidelines.[14]

Advice in the United States

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) in the United States recommends starting with a thiazide diuretic if single therapy is being initiated and another medication is not indicated.

JNC- Seventh Report Recommendations: Medical Management [15]

Table 1:Clinical trial and guideline basis for compelling indications for individual drug classes
Compelling Indication Recommended Drugs Clinical Trial Basis
Heart failure Diuretics, Beta blockers, ACEIs, ARBs, Aldosterone antagonist ACC/AHA Heart Failure Guideline [16]; MERIT-HF [17]; COPERNICUS [18]; CIBIS [19]; SOLVD [20]; AIRE [21]; TRACE [22]; ValHEFT [23]; RALES [24]
Post-Myocardial infarction Beta blockers, ACEIs, Aldosterone antagonist ACC/AHA Post-MI Guideline [25]; BHAT [26]; SAVE [27]; Capricorn [28]; EPHESUS [29]
High coronary disease risk Diuretics, Beta blockers, ACEIs, CCBs, ALLHAT [6]; HOPE [30]; ANBP2 [7]; LIFE [31]; CONVINCE [32]
Diabetes Diuretics, Beta blockers, ACEIs, ARBs, CCBs NKF-ADA Guideline [33][34]; UKPDS [35]; ALLHAT [6]
Chronic kidney disease ACEIs, ARBs NFK Guideline [34]; Captopril Trial [36]; RENAAL [37]; IDNT [38]; REIN [39]; AASK [40]
Recurrent stroke prevention Diuretics, ACEIs PROGRESS [41]

Guidelines Resources

References

  1. ↑ Kragten JA, Dunselman PHJM. Nifedipine gastrointestinal therapeutic system (GITS) in the treatment of coronary heart disease and hypertension. Expert Rev Cardiovasc Ther 5 (2007):643-653. FULL TEXT!
  2. ↑ Materson BJ, Reda DJ, Cushman WC; et al. (1993). "Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents". N. Engl. J. Med. 328 (13): 914–21. PMID 8446138.
  3. ↑ Materson BJ, Reda DJ (1994). "Correction: single-drug therapy for hypertension in men". N. Engl. J. Med. 330 (23): 1689. PMID 8177286. Summary
  4. ↑ Blaufox MD, Lee HB, Davis B, Oberman A, Wassertheil-Smoller S, Langford H (1992). "Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy". JAMA. 267 (9): 1221–5. PMID 1538559.
  5. ↑ Preston RA, Materson BJ, Reda DJ; et al. (1998). "Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents". JAMA. 280 (13): 1168–72. PMID 9777817.
  6. ↑ 6.0 6.1 6.2 ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288 (23):2981-97. PMID: 12479763
  7. ↑ 7.0 7.1 Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL et al. (2003) A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 348 (7):583-92. DOI:10.1056/NEJMoa021716 PMID: 12584366
  8. ↑ Wang TJ, Ausiello JC, Stafford RS (1999) Trends in antihypertensive drug advertising, 1985-1996. Circulation 99 (15):2055-7. PMID: 10209012
  9. ↑ Lewis PJ, Kohner EM, Petrie A, Dollery CT (1976). "Deterioration of glucose tolerance in hypertensive patients on prolonged diuretic treatment". Lancet. 307 (7959): 564–566. PMID 55840.
  10. ↑ Murphy MB, Lewis PJ, Kohner E, Schumer B, Dollery CT (1982). "Glucose intolerance in hypertensive patients treated with diuretics; a fourteen-year follow-up". Lancet. 320 (8311): 1293–1295. PMID 6128594.
  11. ↑ Messerli FH, Williams B,Ritz E (2007). "Essential hypertension". Lancet. 370 (9587): 591–603. PMID.
  12. ↑ Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G (1998) Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet 352 (9136):1252-6. PMID: 9788454
  13. ↑ Sheetal Ladva (28/06/2006). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. Check date values in: |date= (help)
  14. ↑ "Hypertension: management of hypertension in adults in primary care" (PDF). National Institute for Health and Clinical Excellence.
  15. ↑ Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42 (6):1206-52. DOI:10.1161/01.HYP.0000107251.49515.c2 PMID: 14656957
  16. ↑ Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS et al. (2001) ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 38 (7):2101-13. PMID: 11738322
  17. ↑ Tepper D (1999) Frontiers in congestive heart failure: Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Congest Heart Fail 5 (4):184-185. PMID: 12189311
  18. ↑ Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P et al. (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344 (22):1651-8. DOI:10.1056/NEJM200105313442201 PMID: 11386263
  19. ↑ (1994) A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees. Circulation 90 (4):1765-73. PMID: 7923660
  20. ↑ (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 325 (5):293-302. DOI:10.1056/NEJM199108013250501 PMID: 2057034
  21. ↑ (1993) Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet 342 (8875):821-8. PMID: 8104270
  22. ↑ Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K et al. (1995) A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 333 (25):1670-6. DOI:10.1056/NEJM199512213332503 PMID: 7477219
  23. ↑ Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators (2001) A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 345 (23):1667-75. DOI:10.1056/NEJMoa010713 PMID: 11759645
  24. ↑ Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341 (10):709-17. DOI:10.1056/NEJM199909023411001 PMID: 10471456
  25. ↑ Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS et al. (2002) ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 40 (7):1366-74. PMID: 12383588
  26. ↑ (1982) A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA 247 (12):1707-14. PMID: 7038157
  27. ↑ Hager WD, Davis BR, Riba A, Moye LA, Wun CC, Rouleau JL et al. (1998) Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement. Am Heart J 135 (3):406-13. PMID: 9506325
  28. ↑ Dargie HJ (2001) Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 357 (9266):1385-90. PMID: 11356434
  29. ↑ Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348 (14):1309-21. DOI:10.1056/NEJMoa030207 PMID: 12668699
  30. ↑ Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342 (3):145-53. DOI:10.1056/NEJM200001203420301 PMID: 10639539
  31. ↑ Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al. (2002) Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359 (9311):995-1003. DOI:10.1016/S0140-6736(02)08089-3 PMID: 11937178
  32. ↑ Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB et al. (2003) Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 289 (16):2073-82. DOI:10.1001/jama.289.16.2073 PMID: 12709465
  33. ↑ Arauz-Pacheco C, Parrott MA, Raskin P, American Diabetes Association (2003) Treatment of hypertension in adults with diabetes. Diabetes Care 26 Suppl 1 ():S80-2. PMID: 12502624
  34. ↑ 34.0 34.1 National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39 (2 Suppl 1):S1-266. PMID: 11904577
  35. ↑ (1998) Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 317 (7160):713-20. PMID: 9732338
  36. ↑ Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329 (20):1456-62. DOI:10.1056/NEJM199311113292004 PMID: 8413456
  37. ↑ Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH et al. (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345 (12):861-9. DOI:10.1056/NEJMoa011161 PMID: 11565518
  38. ↑ Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al. (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345 (12):851-60. DOI:10.1056/NEJMoa011303 PMID: 11565517
  39. ↑ (1997) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) Lancet 349 (9069):1857-63. PMID: 9217756
  40. ↑ Wright JT, Agodoa L, Contreras G, Greene T, Douglas JG, Lash J et al. (2002) Successful blood pressure control in the African American Study of Kidney Disease and Hypertension. Arch Intern Med 162 (14):1636-43. PMID: 12123409
  41. ↑ PROGRESS Collaborative Group (2001) Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 358 (9287):1033-41. DOI:10.1016/S0140-6736(01)06178-5 PMID: 11589932

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