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Sudden Cardiac Death in Patients with Hypertension

An Association with Diuretics and β-Blockers?

Drug Safety volume 16, pages 233–241 (1997)Cite this article

Summary

The cornerstones of current antihypertensive treatment are diuretics and β-blockers and the efficacy of these drugs in preventing cardiovascular disease is undisputed. This article focuses on the effect of these 2 drug classes on the incidence of sudden death.

Numerous studies have shown that thiazide diuretics have a strong, dosagedependent potassium-depleting effect, and it has been postulated that this may explain why the reduction in risk of coronary heart disease, observed in hypertension trials, was less pronounced than expected. In 7 trials that included sudden death as an end-point, a pooled risk-ratio of sudden death of 1.5 (95% confidence interval 1.1 to 2.0) was observed when non-potassium-sparing diuretics were compared with placebo. Two recent case-control studies have also strongly indicated that the use of thiazides increases the risk of sudden death. Evidence from trials using potassium-sparing diuretic combinations suggests that these may be better tolerated than thiazide monotherapy.

Although it was suggested in the 2 recent case-control studies that recipients of β-blockers are also at an increased risk of sudden death, further studies are required to confirm this finding, particularly since these drugs have several well-documented cardioprotective effects.

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References

  1. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993; 153: 154–83

    Article  Google Scholar 

  2. Sever P, Beevers G, Bulpitt C, et al. Management guidelines in essential hypertension: report of the Second Working Party of the British Hypertension Society. BMJ 1993; 306: 983–7

    PubMed  Article  CAS  Google Scholar 

  3. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke and coronary heart disease: part 2. Effects of short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–38

    PubMed  Article  CAS  Google Scholar 

  4. Singh BN, Hollenberg NK, Poole-Wilson PA, et al. Diuretic-induced potassium and magnesium deficiency: relation to drug-induced QT prolongation, cardiac arrhythmias and sudden death. J Hypertens 1992; 10: 301–16

    PubMed  Article  CAS  Google Scholar 

  5. Kassirer JP, Harrington JT. Fending off the potassium pushers. N Engl J Med 1985; 312: 785–7

    PubMed  Article  CAS  Google Scholar 

  6. Kaplan NM. Our appropriate concern about hypokalemia. Am J Med 1984; 77: 1–4

    PubMed  Article  CAS  Google Scholar 

  7. Siscovick DS, Raghunathan TE, Psaty BM, et al. Diuretic therapy and the risk of primary cardiac arrest. N Engl J Med 1994; 330: 1852–7

    PubMed  Article  CAS  Google Scholar 

  8. Hoes AW, Grobbee DE, Lubsen J, et al. Diuretics, β-blockers, and the risk for sudden cardiac death in hypertensive patients. Ann Intern Med 1995; 123: 481–7

    PubMed  CAS  Google Scholar 

  9. Kendall MJ, Lynch KP, Hjalmarson A, et al. β-Blockers and sudden cardiac death. Ann Intern Med 1995; 123: 358–67

    PubMed  CAS  Google Scholar 

  10. Hoes AW, Grobbee DE, Peet TM, et al. Do non-potassium-sparing diuretics increase the risk of sudden cardiac death in hypertensive patients? Recent evidence. Drugs 1994; 47: 711–33

    PubMed  Article  CAS  Google Scholar 

  11. Papademetriou V. Diuretics, hypokalemia, and cardiac arrhythmias: a critical analysis. Am Heart J 1986; 111: 1217–24

    PubMed  Article  CAS  Google Scholar 

  12. Holland OB, Kuhnert L, Pollard J, et al. Ventricular ectopic activity with diuretic therapy. Am J Hypertens 1988; 1: 380–5

    PubMed  CAS  Google Scholar 

  13. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. II: results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213: 1143–52

    Article  Google Scholar 

  14. Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. JAMA 1974; 229: 409–18

    Article  Google Scholar 

  15. US Public Health Service Hospitals Cooperative Study Group (Smith, W.M.). Treatment of mild hypertension: results of a ten-year intervention trial. Circ Res 1977; 40Suppl. 1: 98–105

    Google Scholar 

  16. Helgeland A. Treatment of mild hypertension: a five year controlled drug trial: the Oslo Study. Am J Med 1908; 69: 725–32

    Article  Google Scholar 

  17. Multiple Risk Factor Intervention Trial Research Group. Multiple Risk Factor Intervention Trial: risk factor changes and mortality results. JAMA 1982; 248: 1465–77

    Article  Google Scholar 

  18. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. BMJ 1985; 291: 97–104

    Article  Google Scholar 

  19. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991; 265: 3255–64

    Article  Google Scholar 

  20. Kannel WB, McGee DL, Schatzkin A. An epidemiological perspective of sudden death. 26-year follow-up in the Framing-ham study. Drugs 1984; 28Suppl. 1: 1–16

    PubMed  Article  Google Scholar 

  21. Amery A, Birkenhäger WH, Brixko P, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; I: 1350–4

    Google Scholar 

  22. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 1992; 304: 405–12

    Article  Google Scholar 

  23. Dahlöf B, Lindholm LH, Hansson L, et al. Morbidity and mortality in the Swedish trial in old patients with hypertension (STOP-Hypertension). Lancet 1991; 338: 1281–5

    PubMed  Article  Google Scholar 

  24. Olsson G, Tuomilehto J, Berglund G, et al. Primary prevention of sudden cardiac death in hypertensive patients: mortality results from the MAPHY Study. Am J Hypertens 1991; 4: 151–8

    PubMed  CAS  Google Scholar 

  25. Hoes AW, Grobbee DE, Lubsen J. Primary prevention in hypertension: valid conclusions from observational studies. Circulation 1990; 84Suppl. VI: 78–83

    Google Scholar 

  26. Miettinen OS. The need for randomization in the study of intended effects. Stat Med 1983; 2: 267–71

    PubMed  Article  CAS  Google Scholar 

  27. Grobbee DE, Hoes AW. Non-potassium-sparing diuretics and risk of sudden cardiac death. J Hypertens 1995; 13: 1539–45

    PubMed  CAS  Google Scholar 

  28. Kannel WB, Cupples A, D’Agostino RB, et al. Hypertension, antihypertensive treatment and sudden cardiac death: the Framingham Study. Hypertension 1988; 11Suppl. II: 45–50

    Google Scholar 

  29. Sytkowski PA, D’Agostino RB, Belanger AJ, et al. Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality: the Framingham Heart Study 1950 to 1990. Circulation 1996; 93: 697–703

    PubMed  Article  CAS  Google Scholar 

  30. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 274: 620–5

    PubMed  Article  CAS  Google Scholar 

  31. Aursnes I, Litleskare I, Frøyland H, et al. Association between various drugs used for hypertension and risk of acute myocardial infarction. Blood Press 1995; 4: 157–63

    PubMed  Article  CAS  Google Scholar 

  32. Furberg CD, Psaty BP, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92: 1326–31

    PubMed  Article  CAS  Google Scholar 

  33. Frohlich ED, Zanchetti A. Antihypertensive therapy: safety and efficacy of drugs and publications. Hypertension 1996; 27 part 1: 317–8

    PubMed  Article  CAS  Google Scholar 

  34. Rajman I, Kendall MJ. Sudden cardiac death and the potential role of beta-adrenoceptor-blocking drugs. Postgrad Med J 1993; 69: 903–11

    PubMed  Article  CAS  Google Scholar 

  35. Hasford J. Compliance and the benefit/risk relationship of antihypertensive treatment. J Cardiovasc Pharmacol 1992; 20Suppl. 6: 30–4

    Google Scholar 

  36. Reithman C, Thomschke A, Werdan K. The role of endogenous noradrenaline in the betablocker withdrawal phenomenon — studies with cultured heart cells. Klin Wochenschr 1987; 65: 308–16

    Article  Google Scholar 

  37. Psaty BM, Koepsell TC, Wagner EH, et al. The relative risk of incident coronary heart disease associated with recently stopping the use of β-blockers. JAMA 1990; 263: 1653–7

    PubMed  Article  CAS  Google Scholar 

  38. To β-block or better block? [editorial]. BMJ 1995; 311: 701–2

  39. Hall JA, Kaumann AJ, Brown MJ. Selective β1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through β2-adrenoceptors in human atrial myocardium. Circ Res 1990; 66: 1610–23

    PubMed  Article  CAS  Google Scholar 

  40. Soriano JB, Hoes AW, Meems L, et al. Increased survival with β-blockers: importance of ancillary properties. Prog Cardiovasc Dis. In press

  41. IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the betablocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens 1985; 3: 379–92

    Article  Google Scholar 

  42. Wilhelmsen L, Berglund G, Elmfeldt D, et al. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J Hypertens 1987; 5: 561–75

    PubMed  Article  CAS  Google Scholar 

  43. Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ 1996; 293: 1145–51

    Article  Google Scholar 

  44. Miall WE, Greenberg G, Brennan P. Further results of the MRC treatment trial for mild hypertension. Nephron 1987; 47Suppl. 1: 111–4

    PubMed  Article  Google Scholar 

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Author information

Affiliations

  1. Julius Center for Patient-Oriented Research, Utrecht University/Academic Hospital Utrecht, Universiteitsweg 100, 3581 CG, Utrecht, The Netherlands

    Arno W. Hoes & Diederick E. Grobbee

  2. Department of General Practice, Utrecht University/Academic Hospital Utrecht, Utrecht, The Netherlands

    Arno W. Hoes

  3. SOCAR Research SA, Givrins, Switzerland

    Jacobus Lubsen

Authors
  1. Arno W. Hoes
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  2. Diederick E. Grobbee
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  3. Jacobus Lubsen
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Correspondence to Arno W. Hoes.

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Hoes, A.W., Grobbee, D.E. & Lubsen, J. Sudden Cardiac Death in Patients with Hypertension. Drug-Safety 16, 233–241 (1997). https://doi.org/10.2165/00002018-199716040-00001

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  • DOI: https://doi.org/10.2165/00002018-199716040-00001

Keywords

  • Sudden Death
  • Sudden Cardiac Death
  • Thiazide
  • Diuretic Therapy
  • Multiple Risk Factor Intervention Trial