Langzeitsicherheit von Blutdrucksenkern

ZUSAMMENFASSUNG

Eine optimale Blutdruckeinstellung ist essenziell, um langfristig kardiorenovaskuläre Schäden zu verhindern und um die kardiovaskuläre Mortalität der Patienten zu reduzieren. Viele blutdrucksenkende Medikamente wurden in den letzten Jahrzehnten sehr erfolgreich entwickelt. Patienten müssen diese z. T. für viele Jahre einnehmen, daher erwartet man von den Medikamenten eine sehr hohe Langzeitsicherheit. Das bedeutet, dass es auch nach Jahrzehnten nicht zu unangenehmen Folgeschäden wie v. a. Krebserkrankungen kommen darf. Denn es gab immer wieder Hinweise, dass bestimmte Medikamente wie Thiaziddiuretika oder auch ACE-Hemmer (ACE: „angiotensin converting enzyme“) das Wachstum spezifischer Krebserkrankungen ggf. steigern oder auch die Entstehung von Tumoren auslösen können. Dieser Beitrag fasst den aktuellen Stand zu Langzeitsicherheit bzw. -nebenwirkungen der typischen Blutdrucksenker wie ACE-Hemmer, Sartane, Kalziumantagonisten, Beta-Blocker und Diuretika zusammen.

Publication History

Article published online:
16 November 2021

• Literatur

• 1 Sipahi I, Debanne SM, Rowland DY. et al Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol 2010; 11: 627-636 DOI: 10.1016/S1470-2045(10)70106-6.
• 2 ARB Trialists Collaboration Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals J Hypertens 2011 29. 623-635 DOI: 10.1097/HJH.0b013e328344a7de
• 3 Pottegård A, Pedersen SA, Schmidt SAJ. et al Association of hydrochlorothiazide use and risk of malignant melanoma. JAMA Intern Med 2018; 178: 1120-1122 DOI: 10.1001/jamainternmed.2018.1652.
• 4 Pottegård A, Hallas J, Olesen M. et al Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 2017; 282: 322-331 DOI: 10.1111/joim.12629.
• 5 Gandini S, Palli D, Spadola G. et al Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis. Crit Rev Oncol Hematol 2018; 122: 1-9 DOI: 10.1016/j. critrevonc.2017.12.003.
• 6 Kristensen KB, Hicks B, Azoulay L. et al Use of ACE (angiotensin-converting enzyme) inhibitors and risk of lung cancer: a nationwide nested case-control study. Circ Cardiovasc Qual Outcomes 2021; 14: e006687 DOI: 10.1161/CIRCOUTCOMES. 120.006687.
• 7 Copland E, Canoy D, Nazarzadeh M. et al Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis. Lancet Oncol 2021; 22: 558-570 DOI: 10.1016/S1470-2045(21)00033-4.
• 8 SOLVD Investigators Yusuf S, Pitt B. et al Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302 DOI: 10.1056/NEJM199108013250501.
• 9 Bangalore S, Kumar S, Kjeldsen SE. et al Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol 2011; 12: 65-82 DOI: 10.1016/S1470-2045(10)70260-6.
• 10 Lever AF, Hole DJ, Gillis CR. et al Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?. Lancet 1998; 352: 179-184 DOI: 10.1016/S0140-6736(98)03228-0.
• 11 Hicks BM, Filion KB, Yin H. et al Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ 2018; 363: k4209 DOI: 10.1136/bmj. k4209.
• 12 Sethi T, Rozengurt E. Multiple neuropeptides stimulate clonal growth of small cell lung cancer: effects of bradykinin, vasopressin, cholecystokinin, galanin, and neurotensin. Cancer Res 1991; 51: 3621-3623
• 13 Ager EI, Neo J, Christophi C. The reninangiotensin system and malignancy. Carcinogenesis 2008; 29: 1675-1684 DOI: 10.1093/carcin/bgn171.
• 14 Volpe M, Azizi M, Danser AH. et al Twisting arms to angiotensin receptor blockers/antagonists: the turn of cancer. Eur Heart J 2011; 32: 19-22 DOI: 10.1093/eurheartj/ehq382.
• 15 Pfeffer MA, Swedberg K, Granger CB. et al Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362: 759-766 DOI: 10.1016/s0140-6736(03)14282-1.
• 16 Gold B, Mirvish SS. N-Nitroso derivatives of hydrochlorothiazide, niridazole, and tolbutamide. Toxicol Appl Pharmacol 1977; 40: 131-6 DOI: 10.1016/0041-008x(77)90124-7.
• 17 Corrao G, Scotti L, Bagnardi V. et al Hypertension, antihypertensive therapy and renal-cell cancer: a meta-analysis. Curr Drug Saf 2007; 2: 125-133 DOI: 10.2174/157488607780598296.
• 18 ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group 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 2002 288. 2981-2997 DOI: 10.1001/jama.288.23.2981
• 19 Monteiro AF, Rato M, Martins C. Drug-induced photosensitivity: Photoallergic and phototoxic reactions. Clin Dermatol 2016; 34: 571-581 DOI: 10.1016/j.clindermatol.2016.05.006.
• 20 Jensen AØ, Thomsen HF, Engebjerg MC. et al Use of photosensitising diuretics and risk of skin cancer: a population-based case-control study. Br J Cancer 2008; 99: 1522-1528 DOI: 10.1038/sj.bjc.6604686.
• 21 Schmidt SA, Schmidt M, Mehnert F. et al Use of antihypertensive drugs and risk of skin cancer. J Eur Acad Dermatol Venereol 2015; 29: 1545-1554 DOI: 10.1111/jdv.12921.
• 22 Pedersen SA, Gaist D, Schmidt SAJ. et al Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018; 78: 673-681.e9 DOI: 10.1016/j.jaad.2017.11.042.
• 23 Faconti L, Ferro A, Webb AJ. et al Hydrochlorothiazide and the risk of skin cancer. A scientific statement of the British and Irish Hypertension Society. J Hum Hypertens 2019; 33: 257-258 DOI: 10.1038/s41371-019-0190-2.
• 24 Pahor M, Guralnik JM, Ferrucci L. et al Calcium-channel blockade and incidence of cancer in aged populations. Lancet 1996; 348: 493-497 DOI: 10.1016/S0140-6736(96)04277-8.
• 25 Li CI, Daling JR, Tang MT. et al Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med 2013; 173: 1629-1637 DOI: 10.1001/jamainternmed.2013.9071.
• 26 Azoulay L, Soldera S, Yin H. et al Use of calcium channel blockers and risk of breast cancer: A population-based cohort study. Epidemiology 2016; 27: 594-601 DOI: 10.1097/EDE.0000000000000483.
• 27 Zhang D, Ma QY, Hu HT. et al β2-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NFκB and AP-1. Cancer Biol Ther 2010; 10: 19-29 DOI: 10.4161/cbt.10.1.11944.
• 28 MRC Working Party Medical Research Council trial of treatment of hypertension in older adults: principal results BMJ 1992 304. 405-412 DOI: 10.1136/bmj.304.6824.405
• 29 Messerli FH, Bangalore S, Bavishi C. et al Angiotensin-converting enzyme inhibitors in hypertension: To use or not to use?. J Am Coll Cardiol 2018; 71: 1474-1482 DOI: 10.1016/j. jacc.2018.01.058.