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Practice recommendations
* In your efforts to reduce cardiovascular events in hypertensive patients, concentrate on getting patients to goal, rather than on which drugs to use to get them there (A).
* Beta-blockers–especially atenolol–should not be the drug of first choice when treating older patients with hypertension (A).
* Multiple drugs are required for adequate blood pressure control in most patients (A).
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

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Forget about a silver bullet.
Researchers have conducted numerous trials over the last decade to find an antihypertensive drug that best reduces cardiovascular events while reducing blood pressure. However, this objective review of 13 comparative antihypertensive drug trials over the past decade involving more than 168,000 patients reveals no great differences in the cardiovascular protective effects of diuretics, beta-blockers, calcium channel blockers, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors.
In fact, this review indicates that there were no significant differences in the primary cardiovascular endpoints in more than 90% of the patients studied. Where a difference in secondary clinical outcome was demonstrated, fewer events consistently occurred in the regimen that reached the lower blood pressure level.
This assessment will likely fly in the face of the way that many would view this body of research. That’s understandable. At first glance, it would appear that these 13 trials, with different methodology and endpoints, have produced conflicting conclusions with the confusion worsened by pharmaceutical companies seeking to interpret the results to best suit their marketing needs. (1-3)
It is not the quality of the data, however, that is in question; the controversy lies in the interpretation. Subjecting the studies to further statistical analysis would simply obscure the information.
By reviewing the data impartially and objectively as a whole, though, and interpreting individual studies in light of similar studies, it becomes evident that there is more consensus than conflict. The studies support the notion that we should concentrate on getting patients to goal, rather than focusing on which drugs we’ll use to get them there.
Methods
I performed a PubMed search of the last 10 years using the keywords hypertension, comparative, drug trials. I supplemented my search with references from the JNC 7, WHO, BHS/NICE, and European hypertension guidelines. For this review, I included only randomized controlled trials with clinical cardiovascular primary endpoints. The studies had to have enrolled at least 500 patients and followed them for at least 3 years. Thirteen trials satisfied these criteria. (4-17) All 13 are summarized in the TABLE, but I will review 5 of the more recent trials here. They are:
* ASCOT-BPLA–Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm
* ALLHAT–Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
* ANBP2–Second Australian National Blood Pressure Study
* LIFE–Losartan Intervention For Endpoint reduction
* VALUE–Valsartan Antihypertensire Long-term Use Evaluation.
Calcium channel blockers vs beta-blockers
ASCOT-BPLA studied 19,257 high-risk hypertensive patients on amlodipine (Norvasc), adding perindopril, or atenolol (Tenormin), adding bendroflumethiazide. (17) After 5.5 years, the primary endpoint of nonfatal myocardial infarction (MI) and cardiovascular death was similar (relative risk [RR] = 0.90; 95% confidence interval [CI], 0.79-1.02; P = .1052).
Total coronary endpoint, stroke, and mortality were all lower on amlodipine. Blood pressure was significantly lower on amlodipine compared with atenolol, with an average difference of 2.7/1.9 mm Hg over the trial duration. (18)
At the end of the trial, patients on amlodipine also had a significantly higher HDL cholesterol, and lower body mass index, triglyceride, creatinine, and glucose levels. However, when researchers made a multivariate adjustment for all of these risk factors, cardiovascular event rate differences between the 2 groups disappeared, underscoring the importance of controlling for all risk factors in reducing clinical cardiovascular events. (18,19)
A careful reading of ASCOT-BPLA, then, makes it clear that this study does not support the notion that newer antihypertensives (calcium channel blockers and ACE inhibitors) are superior to older ones (beta-blockers and diuretics). (20,21) This study actually demonstrates that while blood pressure reduction is vital, the differences between regimens are less important.
Largest hypertensive trial ever studied 4 drugs
ALLHAT, the largest hypertensive trial ever conducted, randomized 15,255 patients to chlorthalidone, 9061 to doxazosin (Cardura), 9048 to amlodipine, and 9054 to lisinopril (Prinivil/Zestril). (10,11) (The arm involving doxazosin was terminated after 3.2 years. (11,22))