Hypertensive blacks, Amlodipine, Lisinopril, Blood pressure control, Sub-saharan africa, Hypertension, Combination therapy. Hypertension is a disease of public health importance worldwide, including Tanzania.
In Tanzania, hypertension is present in As a result, there has been an increase in recorded cardiovascular and renal complications including stroke, left ventricular hypertrophy, heart failure, chronic kidney disease and cardiovascular deaths in the country [ 2 , 3 , 5 - 7 ]; a trend that has also been seen in other parts of the sub Saharan Africa region [ 8 ]. To overcome this trend, better BP control remains one of the most important priorities, as it is the most significant intervention to reduce complications.
However, this task is faced with many challenges including lack of simple, cheap and readily available evidence-informed drug combinations to control hypertension in the local setting. The long-acting dihydropyridines CCBs and long acting ACEIs are good choices for once-a-day dosing as they increase adherence and therefore improve patient compliance and control [ 11 ].
Both drugs have been shown to reduce systolic BP by a factor of up to mmHg as monotherapy in randomized clinical trials [ 12 - 14 ], but some have found ACEI to be less potent than CCBs in lowering BP, especially among hypertensive blacks [ 15 , 16 ]. In the study by Ojji, et al. We aimed to study the level of BP reduction of commonly prescribed drugs in Tanzania; Lisinopril long-acting ACEI and Amlodipine long acting dihydropyridine CCB , each in combination with Bendroflumethiazide thiazide diuretic in patients with moderate to severe hypertension being followed-up in hypertension clinics in 3 district hospitals in Dar es Salaam.
Further, we wanted to compare their effectiveness in hypertension control at 2 and 4-weeks, while assessing their tolerability among patients. This was an open-label, comparative study. The study was conducted between November and January The study was conducted in 3 district hospitals Temeke, Amana and Mwananyamala in Dar es Salaam city.
The hospitals serve as referral hospitals for approximately 90 lower-level health centers within Dar es Salaam. The hypertension clinics are conducted once per week in each of the hospitals and are attended by physicians and 2 nurses. Each clinic sees an average of 50 patients on a clinic day. Participants were hypertensive native Tanzanians attending care and treatment at these hospitals during the time of the study, and who had indications for combination therapy for their hypertension treatment.
Both newly diagnosed and previously known hypertensives were included. The sample size for this study was calculated using the formula for estimating sample sizes for non-inferiority comparative study design comparing two independent group means [ 17 ]. Upon fulfilling the inclusion and exclusion criteria, patients were consecutively enrolled in the study until the required sample size was achieved. After enrollment, patients were required to discontinue any of their previous antihypertensive medications and were started on the combination regime without a wash-out period.
All drugs were on separate tablet formulations, stationed at the hospital pharmacy and were given freely to the study participants. A structured questionnaire was used to record information on patients' socio-demographic and clinical characteristics, including cardiovascular risk factors' history. Information regarding previous and existing cardiovascular diseases like heart failure, chronic kidney disease, etc.
At baseline, BP was taken by using a mercury sphygmomanometer. This was done when the patient had a 5 minutes' rest and seated comfortably in a chair with the back and left arm supported, legs uncrossed and the upper arm at the level of the right atrium. A proper cuff size was used. The first and fifth Korotkoffs' sounds were taken as systolic and diastolic BP respectively. Three measurements were taken one minute apart in the left arm and the average of the last two readings were recorded as the patient's BP.
Only patients who were found to have BP range of grade 2 or more hypertension on the day of clinic visit were included in the study. Height and weight were measured according to standard techniques. Prescribed medications were to be taken the next morning and patients were instructed to take their medications between am to am.
The importance to adhere to the prescribed medications was explained to patients and their caregivers as appropriate. Patients were asked to contact the investigator if they felt any adverse effects. Patients were followed up at their respective clinics in 2- and 4-weeks after initiation of the study medications. During follow-up visits, assessment of patients' adherence was done while history of any side effect was actively asked and recorded.
During each follow-up visit, office BP was measured using same protocol described above, and recorded in patients' data collection forms. The primary endpoint of this study was the mean change in office systolic and diastolic BP from baseline to 4 weeks of treatment.
Secondary endpoints were: proportion of patients who achieved BP control Data were analyzed using statistical package for social sciences SPSS software, version Unpaired Student's t-test was used to compare differences in continuous variables including mean BP between treatment groups, while a two-tailed paired t-test was used to compare the within group BP change i.
All significance tests were two-sided, and a p-value of This study was done in accordance to the Helsinki Declaration of studies on human subjects. This might in part explain why we did not see an antiproteinuric effect during amlodipine treatment. More rigorous lowering of blood pressure with calcium channel blockers, therefore, might have resulted in a decrease in proteinuria in nondiabetic patients as well. Indeed, as stated before, Weidman et al 6 demonstrated, in their metaanalysis on the antiproteinuric effects of antihypertensive agents in diabetic patients, that calcium channel blockers reduce proteinuria only if a substantial fall in blood pressure is achieved.
Likewise, August et al 18 showed in a small number of patients with diverse renal diseases that proteinuria only decreased when blood pressure reduction was attained.
In the amlodipine-treated group two of five patients had only a slight blood pressure response, but lisinopril-treated patients only showed a reduction in blood pressure if proteinuria at baseline was high. In a rat study by Bakris et al 19 the antihypertensive effect of amlodipine was smaller than that of the ACE inhibitor benazepril and decreased with time, while that in the benazepril-treated rats persisted.
Proteinuria was comparable to no treatment in the amlodipine-treated animals whereas benazepril resulted in a significant decrease in proteinuria. Experimental studies have revealed that certain calcium antagonists could be more effective in reducing proteinuria than others.
Pelayo et al 20 demonstrated in rats that the phenylalkylamine calcium channel blocker verapamil reduced proteinuria. The benzothiazepine calcium channel blocker diltiazem reduced proteinuria in diabetic patients. Dihydropyridine-type calcium channel blockers induce vasodilation of afferent arterioles but have no effect on efferent arterioles.
To date no studies have reported on the antiproteinuric effect of verapamil or diltiazem in nondiabetic renal disease. Bakris et al demonstrated that treatment of diabetic patients with either verapamil or diltiazem induces a decrease in proteinuria.
Especially the dihydropyridine calcium channel blocker nifedipine does not affect or even increases proteinuria, whereas other dihydropyridine type calcium channel blockers may reduce proteinuria. Evidence, however, has been gathered on the potential of calcium channel blockers to attenuate mitogenic effects of growth factors, to reduce the metabolic activity of remnant kidneys, to modulate mesangial traffic of macromolecules, and to decrease free radical formation.
In conclusion this double randomized controlled study shows that amlodipine does not affect proteinuria in patients with nondiabetic renal failure with macroproteinuria. In addition we have confirmed that the ACE inhibitor lisinopril induces a substantial decrease in proteinuria, reaching its maximum effect after several weeks of treatment. Kidney Int ; 35 : — Google Scholar. J Clin Invest ; : — Ter Wee PM , Epstein M : Angiotensin-converting enzyme inhibitors and progression of nondiabetic chronic renal disease.
Arch Intern Med ; : — Epstein M : Calcium antagonists and renal protection. Kidney Int ; 34 : — Weidmann P , Schneider M , Bohlen L : Therapeutic efficacy of different antihypertensive drugs in human diabetic nephropathy—an updated metaanalysis. Nephrol Dial Transplant ; 10 : 39 — Nephron ; 52 : 72 — Kloke HJ , Wetzels J.
M , van Hamersvelt HW et al. J Cardiovasc Pharmacol ; 16 : — Contrib Nephrol ; 90 : — Curr Ther Res ; 53 : — Am J Nephrol ; 11 : — Kidney Int ; 42 : — Kidney Int ; 32 : 78 — Donker A. Neth J Med ; 20 : 97 — Kidney Int ; 36 : — Diabetes ; 39 : 76 — Nephrol Dial Transplant ; 10 : — August P , Lenz T , Laragh JH : Comparative renal hemodynamic effects of lisinopril, verapamil, and amlodipine in patients with chronic renal failure.
Am J Hypertens ; 6 : S — S. J Hypertens ; 15 : — Am J Physiol ; : F — F Bakris GL : Effects of diltiazem or lisinopril on massive proteinuria associated with diabetes mellitus. Ann Intern Med ; : — Tarif N , Bakris GL : Preservation of renal function: the spectrum of effects by calcium-channel blockers. Nephrol Dial Transplant ; 12 : — Kidney Int ; 50 : — Hypertension ; 29 : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Patients and Methods. M Janssen , J. M Janssen. Oxford Academic. B Gans. J van der Meulen. R Pijpers. M ter Wee. Warning You have reached the maximum number of saved studies Listing a study does not mean it has been evaluated by the U.
Federal Government. Read our disclaimer for details. Recruitment status was: Not yet recruiting First Posted : April 19, Last Update Posted : April 19, Study Description. This study seeks to compare the differences in effectiveness among individual patients treated at for hypertension with bedtime administration of amlodipine versus lisinopril. There will be an analysis of whether one medication was more effective than another and whether specific patient factors could predict who responded better to which one.
Drug Information available for: Lisinopril Amlodipine Amlodipine besylate. FDA Resources. Arms and Interventions. Outcome Measures.
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