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Background: Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic., Methods: Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration., Results: Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011., Conclusions: NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.

We investigated the effects of different antihypertensive drugs on the ambulatory arterial stiffness index (AASI), pulse pressure (PP), the arterio-ventricular coupling index (AVCI) and aortic pulse wave velocity (aPWV). After a 4-week placebo period, 94 and 107 patients with uncomplicated hypertension were randomly assigned to treatment with atenolol (AT) at dosage of 50 mg per day or perindopril/indapamide (PER/IND) at dosage of 2/0.6 mg per day for 1 year. From each patient's 24-h ambulatory blood pressure (BP) recording, we determined the 24-h systolic and diastolic BPs. We computed PP as the difference between 24-h systolic and diastolic BP, AASI as unity minus the regression slope of diastolic on systolic BP, and AVCI as (T/τ)/(1+2T/3τ), where T is the heart period in seconds and τ is the decay time of aortic BP during diastole. On AT compared with PER/IND, with adjustments applied for covariables, 24-h systolic BP (-9.5 vs. -13.7 mm Hg; P=0.009) and 24-h PP (-1.02 vs. -6.53 mm Hg; P<0.001) decreased less and AVCI lengthened more (+0.019 vs. -0.008; P<0.001). The changes in AASI (-0.001 vs. -0.014; P=0.44) and aPWV (-0.89 vs. -0.69 m s(-1); P=0.45) were similar in the two treatment groups. AASI and aPWV showed significant concordance (r=0.21, P=0.003) after adjustment for covariables. On administration of antihypertensive drugs with different hemodynamic profiles, AASI and aPWV behaved similarly. The similarity in the findings for aPWV and AASI support the use of AASI as an index reflecting the arterial stiffness.

Long-term follow-up of clinical trials of blood pressure-lowering medications has suggested a continuation of event reduction after study completion. We evaluated the persistence of mortality benefit of these agents after the end of clinical trials, when all of the patients were advised to take the same open-label therapy. We performed a meta-analysis of randomized clinical trials using blood pressure-lowering medications, used in patients with hypertension, myocardial infarction, or left ventricular systolic dysfunction, (n=18; 132 854 patients; 11 988 deaths) when a second report describing results after the end of the trial was available. During the randomized (first) phase, 80% (interquartile range: 75% to 83%) of the patients randomized to receive active therapy actually received it compared with 16% (interquartile range: 7% to 22%) of those randomized to control. In this phase, mortality was lower in the intervention group (odds ratio: 0.84 [95% CI: 0.79 to 0.90]; P<0.0001). Mortality was also lower during the open-label follow-up (second) phase (odds ratio: 0.85 [95% CI: 0.79 to 0.91]; P<0.0001), when all of the patients were advised to take the same therapy, and rates of receiving active therapy were similar in the 2 groups (59% [interquartile range: 46% to 77%], among those originally randomized to active, and 43% [interquartile range: 20% to 68%], in the control). Several sensitivity analyses indicated stability of the effects. In studies of antihypertensive medications, a decrease in overall mortality persists after the end of trial phase, when most patients in both the intervention and control groups receive active therapy. These analyses imply that earlier intervention would result in better clinical outcomes.

We reviewed 6 recent outcome trials of blood pressure (BP)-lowering drugs in 74,524 randomized hypertensive or high-risk patients. Over interpretation of nonsignificant or marginal probability values in large trials with overlapping end points, exclusion of patients not tolerating or not adhering to experimental treatments, labeling nonsignificant treatment effects as modest, and insufficient information on the quality of the BP measurements or on the BP changes early after randomization raise concern. From a clinical viewpoint, results should not be extrapolated to patients with characteristics dissimilar from those randomized. The benefit beyond BP lowering in cardiovascular prevention is tiny. Dual inhibition of the renin system should only be used in patients at high risk, in whom all drug combinations have been tried and who cannot be controlled by a single renin system inhibitor. Current evidence does not support BP lowering in normotensive patients or the use of renin system inhibitors for prevention of stroke recurrence. Because angiotensin-receptor blockers might offer less protection against myocardial infarction than angiotensin-converting enzyme inhibitors, the latter should remain the preferred renin system inhibitor for cardiovascular prevention in angiotensin-converting enzyme inhibitor-tolerant patients. In 2 trials, in which new-onset diabetes was a predefined end point, 1000 patients had to be treated for 1 year with an angiotensin-receptor blocker instead of placebo to prevent just 2 cases. From a design viewpoint, the time has come to revise the concept of large simple trials and to pursue research questions that serve patient interests more than showing noninferiority or highlight the ancillary qualities of marketable antihypertensive drugs.

Background: The current literature supports the immediate use of combinations of antihypertensive drugs in terms of ease of use and adherence, but the key issue whether combination therapy is more effective than monotherapy in the prevention of cardiovascular complications remains unproven., Methods: We analysed the double-blind (median follow-up 2.0 years) and open follow-up (6.0 years) phases of the Systolic Hypertension in Europe trial. Patients were 60 years or more with an entry systolic/diastolic blood pressure (BP) of 160-219/less than 95 mmHg. Antihypertensive treatment started immediately after randomization in the active-treatment group, but only after completion of the double-blind trial in control patients. Treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day). We adjusted our analyses for sex, age, history of cardiovascular complications, baseline systolic BP and previous antihypertensive treatment., Results: During the double-blind trial, adding enalapril to nitrendipine (n = 515), compared with the equivalent combination of placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032), with similar trends for stroke (-51%; P = 0.066) and cardiac events (-44%; P = 0.075). Over the whole duration of follow-up, combination therapy (n = 871), compared with nitrendipine monotherapy (n = 1552), decreased systolic BP by 3.1 mmHg and reduced total mortality (-32%; P = 0.023), with similar trends for all cardiovascular events (-23%; P = 0.081) and stroke (-42%; P = 0.054)., Conclusion: Despite the limitations of a posthoc analysis, but congruent with the stronger BP reduction, our results suggest that combination therapy with nitrendipine plus enalapril might improve outcome over and beyond the benefits seen with nitrendipine monotherapy.

Purpose of Review: We examined the role of blood pressure-lowering compared with class-specific properties of antihypertensive drugs in cardiovascular prevention., Recent Findings: We reviewed recently published trials and meta-regression analyses., Summary: From 150,000 to 180,000 randomized patients followed up from 3 to 5 years were required to demonstrate a 10-15% benefit 'beyond blood pressure lowering' of newer antihypertensive drugs, such as calcium channel blockers or angiotensin-converting enzyme inhibitors in the prevention of cause-specific cardiovascular complications. Assuming an absolute risk of new-onset diabetes mellitus on older drugs of approximately 10% over 5 years and a relative benefit on the newer drugs of approximately 30%, about 100 patients would have to be treated for 5 years with the newer agents to avert approximately three iatrogenic cases of diabetes. Whether or not new-onset diabetes is associated with increased risk is uncertain. In most patients, optimization of treatment at acceptable tolerance requires rotation through and combination of several drug classes. Combination of different classes of antihypertensive drugs not only enhances the blood pressure-lowering efficacy, but likely decreases the risk of metabolic adverse effects as well. True benefit beyond blood pressure lowering in hypertensive patients comes from multiple risk factor intervention.

The author reflects on the efficiency of ACE inhibitors used in clinical practice in Great Britain for lowering blood pressure and for preventing cardiovascular and renal complications. He cites that the UK National Institute for Clinical Excellence 2006 guidelines suggested on the application of drugs for initiating antihypertensive treatment in patients younger than 55 years of age. He concluded that imidapril has more favorable adverse-event profile with less dry cough than other compounds.

The authors reflect on the use of hypotensive agents to reduce hypertension in patients and on research which has been done on them. They suggest that the benefits of the drugs increase with age and that they help manage overall cardiovascular risk. They argue that certain hypertension drugs may be more effective on people in different age groups.